| 1. | Kure, Shoko; Iida, Shinya; Yamada, Marina; Takei, Hiroyuki; Yamashita, Naoyuki; Sato, Yuji; Miyashita, Masao In: Biology, vol. 10, no. 6, pp. 517, 2021, ISSN: 2079-7737. @article{Kure2021,Background: Breast cancer is a leading cause of cancer death worldwide. Several studies have demonstrated that dogs can sniff and detect cancer in the breath or urine sample of a patient. This study aims to assess whether the urine sample can be used for breast cancer screening by its fingerprints of volatile organic compounds using a single trained sniffer dog. This is a preliminary study for developing the “electronic nose” for cancer screening. Methods: A nine-year-old female Labrador Retriever was trained to identify cancer from urine samples of breast cancer patients. Urine samples from patients histologically diagnosed with primary breast cancer, those with non-breast malignant diseases, and healthy volunteers were obtained, and a double-blind test was performed. Total of 40 patients with breast cancer, 142 patients with non-breast malignant diseases, and 18 healthy volunteers were enrolled, and their urine samples were collected. Results: In 40 times out of 40 runs of a double-blind test, the trained dog could correctly identify urine samples of breast cancer patients. Sensitivity and specificity of this breast cancer detection method using dog sniffing were both 100%. Conclusions: The trained dog in this study could accurately detect breast cancer from urine samples of breast cancer patients. These results indicate the feasibility of a method to detect breast cancer from urine samples using dog sniffing in the diagnosis of breast cancer. Although the methodological standardization is still an issue to be discussed, the current result warrants further study for developing a new breast cancer screening method based on volatile organic compounds in urine samples. |
| 2. | Kaneya, Yohei; Takata, Hideyuki; Wada, Ryuichi; Kure, Shoko; Ishino, Kousuke; Kudo, Mitsuhiro; Kondo, Ryota; Taniai, Nobuhiko; Ohashi, Ryuji; Yoshida, Hiroshi; Naito, Zenya In: Oncology Letters, vol. 21, no. 1, pp. 1–8, 2021, ISSN: 17921082. @article{Kaneya2021,mTOR is involved in the proliferation of liver cancer. However, the clinical benefit of treatment with mTOR inhibitors for liver cancer is controversial. Protein disulfide isomerase A member 3 (PDIA3) is a chaperone protein, and it supports the assembly of mTOR complex 1 (mTORC1) and stabilizes signaling. Inhibition of PDIA3 function by a small molecule known as 16F16 may destabilize mTORC1 and enhance the effect of the mTOR inhibitor everolimus (Ev). The aim of the present study was to elucidate the usefulness of combination treatment with Ev and 16F16 in liver cancer using cultured Li‑7 and HuH‑6 cells. The proliferation of cultured cells was examined following treatment with 0.01 µM Ev, 2 µM 16F16 or both. The expression levels and phosphoryla‑ tion of S6 kinase (S6K) and 4E‑binding protein 1 (4E‑BP1) were examined by western blotting. Li‑7 was susceptible to Ev, and proliferation was reduced to 69.5±7.2% by Ev compared with that of untreated cells. Proliferation was reduced to 90.2±10.8% by 16F16 but to 62.3±12.2% by combination treat‑ ment with Ev and 16F16. HuH‑6 cells were resistant to Ev, and proliferation was reduced to 86.7±6.1% by Ev and 86.6±4.8% by 16F16. However, combination treatment suppressed prolif‑ eration to 57.7±4.0%. Phosphorylation of S6K was reduced by Ev in both Li‑7 and HuH‑6 cells. Phosphorylation of 4E‑BP1 was reduced by combination treatment in both Li‑7 and HuH‑6 cells. Immunoprecipitation assays demonstrated that PDIA3 formed a complex with 4E‑BP1 but not with S6K. The small molecule 16F16 increased susceptibility to Ev in cultured liver cancer cells, which are resistant to Ev. The inhibition was associated with reduction of 4E‑BP1 phosphorylation, which formed a complex with PDIA3. Combination treatment with Ev and 16F16 could be a novel therapeutic strategy for liver cancer. |
Accordion Sample Description
Accordion Sample Description
| 1. | MINAGAWA, YUKI; ISHINO, KOUSUKE; WADA, RYUICHI; KUDO, MITSUHIRO; NAITO, ZENYA; TAKESHITA, TOSHIYUKI; OHASHI, RYUJI High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma Journal Article In: Anticancer Research, vol. 40, no. 10, pp. 5631–5639, 2020, ISSN: 0250-7005. @article{MINAGAWA2020,Background/Aim: DNA damage response (DDR), wherein p21 is a cell fate determinant, is a potential cancer therapeutic target. Molecular expression during DDR was explored in ovarian clear-cell carcinoma (CCC). Materials and Methods: CHK1, CHK2, TP53 and p21 expression in DDR was examined using immunostaining in surgical sections of CCC (n=22). Molecular alterations in two types of CCC cell lines, JHOC-5 and JHOC-9, were investigated using western blot analysis. Results: Expression of DDR-associated molecules was noted in most patients. While high p21 expression was found in half of the patients, the remaining patients exhibited low p21 expression. Treatment with UC2288, a p21 inhibitor, attenuated proliferation of both cell lines, more prominently in JHOC-9, resulting in reduced viability and subsequent apoptosis. Conclusion: p21 Inhibitor induced cell death in cells with high p21 expression, suggesting that p21 suppression can be a therapeutic strategy to treat patients with CCC. |
| 2. | Tsunoda, Youhei; Kudo, Mitsuhiro; Wada, Ryuichi; Ishino, Kousuke; Kure, Shoko; Sakatani, Takashi; Takeshita, Toshiyuki; Naito, Zenya Expression level of long noncoding RNA H19 of normotensive placentas in late pregnancy relates to the fetal growth restriction Journal Article In: Journal of Obstetrics and Gynaecology Research, vol. 46, no. 7, 2020, ISSN: 14470756. @article{Tsunoda2020,Aim: Infants with fetal growth restriction (FGR) are at an increased risk of perinatal morbidity and mortality. The long noncoding RNA H19 gene is expressed abundantly in placental villi and recent studies suggest that it regulates FGR. However, the role of H19 in the FGR placenta remains unclear. This study aimed to clarify the relationship between H19 expression and FGR using normotensive placentas after 34 weeks of gestation. Methods: Formalin-fixed paraffin-embedded tissues from human placentas collected from pregnancies resulting in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns were used. The histopathological features of placenta tissues, such as villous stromal fibrosis, the numbers of terminal villi, villous vessels and cytotrophoblasts were analyzed using hematoxylin and eosin, Masson's trichrome staining and immunostaining. The localization and expression of H19 in the placentas were demonstrated by in situ hybridization and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Moreover, the expression levels of H19-regulated molecules such as IGF2 and decorin (DCN) were measured by RT-qPCR. Results: Histopathological features of the placental villous were not different between placentas associated with SGA and AGA. H19 localized to the villous stroma, endothelial cells and cytotrophoblasts. Moreover, the expression level of H19 in SGA placentas was significantly lower than that in AGA placentas. The expression levels of IGF2 and DCN in SGA placentas tended to be lower than those in AGA placentas similarly to H19. Conclusion: This study highlights the potential importance of regulatory events mediated by H19 in SGA placentas without histopathological abnormalities in late pregnancy. |
| 3. | Ishida, Mariko; Matsune, Shoji; Wakayama, Nozomu; Ohashi, Ryuji; Okubo, Kimihiro Possibility of Local Allergic Rhinitis in Japan Journal Article In: American Journal of Rhinology and Allergy, vol. 34, no. 1, pp. 26–34, 2020, ISSN: 19458932. @article{Ishida2020,Background: The concept of local allergic rhinitis (LAR) has been advocated recently. Allergic rhinitis in Japan is characterized by house dust mites (HDMs) and Japanese cedar pollen (JCP). To investigate LAR in Japan, total IgE and antigen-specific IgE (sIgE) were measured in inferior turbinate mucosa and their relationships with skin test (ST) and nasal allergen provocation test (NAPT) and as well as serum IgE levels were examined. Methods: Subjects were 50 rhinosinusitis patients for surgery. ST was performed and serum total IgE and sIgE levels were measured preoperatively. Patients with class-0 serum anti-HDM or anti-JCP sIgE levels were subjected to NAPT with HDM or JCP, respectively, or both. In all patients, inferior turbinate mucosa was weighed and mashed, and total IgE and sIgE levels were then measured as local mucosal date per gram and per milligram. Because there is no clinical consensus how to evaluate nasal sIgE yet, both positive NAPT and detectable sIgE in obtained nasal mucosa were adopted as the diagnostic criteria of LAR in order to strictly elucidate the possibility of presence of LAR in Japan. Results: JCP LAR was definitely diagnosed in 2 of 14 patients (14.3%) and HDM LAR in 5 of 21 (23.8%) in cases with rhinosinusitis symptoms in the absence of positive ST nor serum sIgE. Conclusion: The present results positively support LAR by HDM or JCP being present in Japan. |
| 4. | Uchimura, Ryoichi; Ueda, Takahiro; Fukazawa, Ryuji; Hayakawa, Jun; Ohashi, Ryuji; Nagi-Miura, Noriko; Ohno, Naohito; Migita, Makoto; Itoh, Yasuhiko Adipose tissue-derived stem cells suppress coronary arteritis of Kawasaki disease in vivo Journal Article In: Pediatrics International, vol. 62, no. 1, pp. 14–21, 2020, ISSN: 1442200X. @article{Uchimura2020,Background: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. Methods: Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. Results: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P textless 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1$beta$, IL-12, IL-17, RANTES, INF-$gamma$, and TNF-$alpha$, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. Conclusions: These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD. |
| 1. | Kuwabara, Yoshimitsu; Yonezawa, Mirei; Kubota, Yumene; Ichikawa, Tomoko; Ohashi, Ryuji; Takeshita, Toshiyuki Unique Clinical and Histological Features of Placental Mesenchymal Dysplasia Complicated by Severe Preeclampsia in the Midtrimester Journal Article In: AJP Reports, vol. 10, no. 1, pp. E113–E117, 2020, ISSN: 21577005. @article{Kuwabara2020,Detailed clinical and pathological features of placental mesenchymal dysplasia (PMD) complicated by preeclampsia (PE) are unknown. A 39-year-old nulliparous woman was referred at 19 weeks gestation. Ultrasound examination identified a fetus with severe growth restriction (-2.8 SD) and a markedly thickened placenta with many cystic structures suggestive of PMD. At 21 weeks, the patient developed severe hypertension (180/95 mm Hg) with marked proteinuria and an elevated serum soluble fms-like tyrosine-kinase-1 (sFlt-1) level (47,000 pg/L). The pregnancy was terminated to protect maternal health. Placental weight was 450 g and no histopathological findings of either proliferation or dysplasia were observed in the trophoblast. Villous chromosome examination revealed a 46XX karyotype, consistent with the diagnosis of PMD. In addition to the pathological findings of vascular endothelial dysfunction characteristic of the placenta in PE cases, enhanced expression of sFlt-1 in the syncytiotrophoblast of the enlarged villi was confirmed by immunohistochemistry as a novel finding in this condition. Monitoring of the serum sFlt-1 value is suggested to be a useful predictor of the pathological change associated with extremely early severe PE in PMD cases. |
| 1. | Ohashi, Ryuji Solid variant of papillary thyroid carcinoma: an under-recognized entity Journal Article In: Endocrine Journal, vol. 67, no. 3, pp. 241–248, 2020, ISSN: 0918-8959. @article{Ohashi2020,Solid variant of papillary thyroid carcinoma (SVPTC) is a rare morphological variant of papillary thyroid carcinoma (PTC). SVPTC is histologically characterized by predominant solid, trabecular and insular nests of tumor cells while cytological features of PTC such as nuclear grooves and nuclear inclusions are preserved. In fine needle aspiration cytology smears, tumor cells of SVPTC may be presented in cohesive, syncytial or trabecular clusters accompanied by some discohesiveness in the absence of necrosis. Although SVPTC and poorly differentiated thyroid carcinoma (PDTC) share similar histological findings of solid nests, SVPTC can be differentiated from PDTC in the lack of tumor necrosis, severe nuclear atypia, and a higher mitotic index. Immunohistochemical expression of CK19 and HBME-1, common markers of PTC, is decreased in solid nests of SVPTC. In pediatric patients exposed to radiation after the Chernobyl nuclear accident, there was a higher prevalence of SVPTC with RET/PTC3 type rearrangement. BRAF mutations are also reported in a small number of adult patients with SVPTC without any prior radiation exposure. Patients with SVPTC may have a slightly higher incidence of metastasis and recurrence of the tumor compared to conventional PTC, although overall survival rate is comparable. In this article, the current knowledge of SVPTC will be reviewed and discussed with an emphasis on the histopathological feature. |
| 1. | Kure, Shoko; Wada, Ryuichi; Naito, Zenya Relationship between genetic alterations and clinicopathological characteristics of papillary thyroid carcinoma Journal Article In: Medical Molecular Morphology, vol. 52, no. 4, pp. 181–186, 2019, ISSN: 18601499. @article{Kure2019,Papillary thyroid carcinoma (PTC) is characterized by proliferation of follicular cells with distinctive nuclear features such as ground glass appearance, nuclear groove and pseudoinclusion. From the proliferation pattern, PTC is divided into several histological subtypes; conventional histology is classified as papillary type, and there are also follicular and solid variants. PTC is heterogeneous in genetic alterations. PTC with BRAF mutation presents a histology of conventional PTC, and follows an aggressive clinical course. Most cases of PTC with RAS mutation show a follicular variant, and prognosis is favorable. RET/PTC1 is observed sporadically and in young cases, and prognosis is favorable. RET/PTC3 is associated with radiation exposure, and the solid variant is frequent. ETV6-NTRK3 may be associated with radiation exposure, and the clinical course is aggressive. Mutation in the telomerase reverse transcriptase promoter is observed in PTC cases involving elderly male patients. Tumor size is large, associated with distant metastasis and advanced stage. This mutation is found concomitantly with BRAF mutation, and the clinical course is aggressive. Genetic alterations form subsets of PTC with distinct clinicopathological features. Careful assessment of clinicopathological features is considered useful in predicting clinical course and when planning treatment. |
| 2. | Hotta, Masahiro; Sakatani, Takashi; Ishino, Kousuke; Wada, Ryuichi; Kudo, Mitsuhiro; Yokoyama, Yasuyuki; Yamada, Takeshi; Yoshida, Hiroshi; Naito, Zenya In: Biochemical and Biophysical Research Communications, vol. 519, no. 4, pp. 824–831, 2019, ISSN: 10902104. @article{Hotta2019,Farnesoid X receptor (FXR) exhibits critical anti-cancer functions in several types of cancer, including colorectal cancer, in vitro and in vivo. However, the underlying mechanism remains unclear. We evaluated pharmacological activation of FXR with the synthetic agonist GW4064 using comprehensive proteomic analysis in colorectal cancer cell lines (HCT116, SW480, and DLD1). Among the commonly detected proteins in all three cell lines, death receptor 5 (DR5) was the most up-regulated protein, and key autophagy-related proteins, such as microtubule-associated protein 1 light chain 3 alpha/beta (MLP3A/3B) and p62 sequestosome-1 (SQSTM), were also differentially expressed. Western blot analysis showed that GW4064 stimulation induced activation of the extrinsic death signaling pathway in all cell lines and induced activation of the intrinsic death signaling pathway in DLD1 cells. Western blotting showed that DR5 up-regulation was associated with inhibition of autophagic activity. These results suggest that FXR activation induced DR5 up-regulation through inhibition of autophagic activity and the DR5-related death signaling pathway. In addition, DR5 selective ligand, also known as TRAIL, has been widely used for anti-cancer treatment in several clinical trials. Co-treatment of TRAIL with GW4064 synergistically inhibited colorectal cancer cell proliferation as compared with single treatments. To the best of our knowledge, our results provide novel insights into FXR function in cancer cell lines. These findings may contribute to a new therapeutic strategy for colorectal cancer. |
| 3. | Shimoda, Tomohiro; Wada, Ryuichi; Kure, Shoko; Ishino, Kousuke; Kudo, Mitsuhiro; Ohashi, Ryuji; Fujita, Itsuo; Uchida, Eiji; Yoshida, Hiroshi; Naito, Zenya Expression of protein disulfide isomerase A3 and its clinicopathological association in gastric cancer Journal Article In: Oncology Reports, vol. 41, no. 4, pp. 2265–2272, 2019, ISSN: 17912431. @article{Shimoda2019,Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that supports the folding and processing of synthesized proteins. Its expression is associated with the prognosis of laryngeal cancer, hepatocellular carcinoma, diffuse glioma and uterine cervical cancer. In the present study, the expression levels of PDIA3 and its clinicopathological association were examined in 52 cases of gastric cancer (GC). The expression of PDIA3 was examined by immunohistochemistry and scored using a semi-quantitative method. According to the score, GC samples were classified into PDIA3‑High and PDIA3‑Low GC. PDIA3‑High GC samples were predominantly of the intestinal type. Multivariate survival analysis indicated that PDIA3 expression and cancer stage were independent factors. The overall survival of PDIA3‑High GC cases was significantly favorable compared with that of PDIA3‑Low GC cases, and this was more evident in cases at an advanced stage. In GC cell cultures, the PDIA3 and major histocompatibility complex (MHC) class I proteins were expressed in three out of the four assessed cell lines according to western blot analysis. Notably, the expression of MHC class I was increased by the stimulation of interferon $gamma$. Co-immunoprecipitation assays suggested the formation of a PDIA3 and MHC class I complex. The findings suggested that PDIA3 may be involved in the immune response of carcinoma cells. The improved prognosis in PDIA3‑High GC may be accounted for, in part, by sufficient antigen processing and expression of MHC class I, which can be mediated by PDIA3. It was suggested that PDIA3 serves an important role in the pathobiology of GC, and that PDIA3 is a useful marker for the prediction of prognosis. |
| 4. | Kondo, Ryota; Ishino, Kousuke; Wada, Ryuichi; Takata, Hideyuki; Peng, Wei‑Xia; Kudo, Mitsuhiro; Kure, Shoko; Kaneya, Yohei; Taniai, Nobuhiko; Yoshida, Hiroshi; Naito, Zenya In: International Journal of Oncology, vol. 54, pp. 1409–1421, 2019, ISSN: 1019-6439. @article{Kondo2019, |
| 5. | Yokoyama, Yasuyuki; Wada, Ryuichi; Ishino, Kousuke; Kudo, Mitsuhiro; Koizumi, Michihiro; Yamada, Takeshi; Yoshida, Hiroshi; Naito, Zenya; Sakatani, Takashi In: International Journal of Oncology, vol. 55, no. 6, pp. 1361–1371, 2019, ISSN: 17912423. @article{Yokoyama2019,There is no predictive biomarker for response to 5‑fluorouracil (5FU)‑based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non‑coding RNAs (lncRNAs) linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU‑susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31 cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17 cases, whereas the ratios were high in 14 cases; 11 of the 17 cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14 cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU‑based NAC in rectal cancer. |
| 1. | Ohashi, Ryuji Editorial comment on the fate of full-house immunofluorescence staining in renal allograft: A case report Journal Article In: Pathology International, vol. 69, no. 11, pp. 661, 2019, ISSN: 14401827. @article{Ohashi2019, |
| 2. | Yasukawa, Minoru; Kitagawa, Sachiko; Togashi, Ryo; Asakawa, Shinichiro; Nagura, Michito; Arai, Shigeyuki; Yamazaki, Osamu; Tamura, Yoshifuru; Kondo, Fukuo; Ohashi, Ryuji; Uchida, Shunya; Shibata, Shigeru; Fujigaki, Yoshihide A patient with MPO-ANCA-positive IgA nephropathy diagnosed with the clinical onset of macrohematuria Journal Article In: Internal Medicine, vol. 58, no. 14, pp. 2051–2056, 2019, ISSN: 13497235. @article{Yasukawa2019,A 21-year-old woman presented with renal dysfunction during macrohematuria. A kidney biopsy revealed IgA nephropathy with a small percentage of crescent formation and macrohematuria-associated tubular injury. Macrohematuria-associated acute kidney injury could explain her renal dysfunction. However, she was seropositive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) and showed fibrin deposition around one arteriole. Corticosteroids and mycophenolate mofetil were administered as for ANCA vasculitis, and the serum creatinine, abnormal urinalysis and MPO-ANCA titer all gradually ameliorated. The presence of extra-glomerular vasculitis, which was probably induced by ANCA, suggested that MPO-ANCA was an exacerbating factor for her prolonged renal dysfunction. This condition has so far only rarely been addressed in ANCA-positive IgA nephropathy. |
| 3. | Motoda, Norio; Onda, Munehiko; Nakamizo, Munenaga; Ohashi, Ryuji; Okubo, Kimihiro; Naito, Zenya Crystalloid Granuloma of Parotid Gland: A Case Report With Review of the Literature Journal Article In: International Journal of Surgical Pathology, vol. 27, no. 2, pp. 216–220, 2019, ISSN: 19402465. @article{Motoda2019,Crystalloid granuloma (CG) of salivary gland is an extremely rare inflammatory disease, and only 6 cases have been reported in the English literature. CG is histologically characterized by a granulomatous reaction to amylase crystalloid deposition. A 73-year-old woman presented with a painful left neck mass. Computed tomography depicted a mass located in the lower pole of the left parotid gland, suspicious for a tumoral lesion. Preoperative fine needle aspiration cytology found amylase crystalloid deposition with a few inflammatory cells. Surgical sections of the mass revealed formation of a granuloma containing abundant eosinophilic but glassy and transparent amorphous crystalloids, suggestive of $alpha$-amylase crystalloid. No neoplastic elements were detected. The case was eventually diagnosed with CG in the parotid gland. Our findings suggest that when we identify amylase crystalloids in fine needle aspiration cytology smears from the salivary gland, CG should be considered even if neoplasm is clinically or radiographically suspected. |
| 4. | WX, Peng; R, Wada; S, Kure; M, Fukunaga; Z, Naito Superficial Myofibroblastoma in the Vulva Mimicking Aggressive Angiomyxoma: A Case Report and Review of the Literature Journal Article In: Case reports in pathology, vol. 2019, 2019, ISSN: 2090-6781. @article{WX2019, |
| 5. | F, Honma; Y, Fujigaki; Y, Nemoto; H, Kikuchi; M, Nagura; S, Arai; K, Ishizawa; O, Yamazaki; Y, Tamura; F, Kondo; R, Ohashi; S, Uchida; S, Shibata In: Case reports in nephrology, vol. 2019, 2019, ISSN: 2090-6641. @article{F2019, |
| 6. | R, Togashi; Y, Nemoto; K, Waki; M, Nagura; S, Arai; Y, Tamura; Y, Oshima; F, Kondo; R, Ohashi; S, Uchida; S, Shibata; Y, Fujigaki In: Case reports in nephrology, vol. 2019, 2019, ISSN: 2090-6641. @article{R2019, |
| 1. | Kanzaki, Go; Okabayashi, Yusuke; Nagahama, Kiyotaka; Ohashi, Ryuji; Tsuboi, Nobuo; Yokoo, Takashi; Shimizu, Akira Monoclonal Immunoglobulin Deposition Disease and Related Diseases Journal Article In: Journal of Nippon Medical School, vol. 86, no. 1, pp. 2–9, 2019, ISSN: 1345-4676. @article{Kanzaki2019,Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components are constituted by light chain (myeloma) cast nephropathy, light chain associated Fanconi's syndrome (light chain proximal [crystal] tubulopathy), and crystal-storing histiocytosis. In the present review article, we demonstrate the clinicopathological characteristics of MIDD, which is one of the representative diseases of plasma cell dyscrasias, and discuss various renal diseases with the deposition of monoclonal immunoglobulins or their components in glomeruli and the tubulointerstitium. We recommend that these renal diseases are arranged as one disease category, “renal diseases with deposition of monoclonal immunoglobulins or their components”, in order to simplify the understanding of complicated diseases in plasma cell dysplasia. |
1.
Ohashi, Ryuji; Namimatsu, Shigeki; Sakatani, Takashi; Naito, Zenya; Takei, Hiroyuki; Shimizu, Akira
Prognostic utility of atypical mitoses in patients with breast cancer: A comparative study with Ki67 and phosphohistone H3 Journal Article
In: Journal of Surgical Oncology, vol. 118, no. 3, pp. 557–567, 2018, ISSN: 10969098.
@article{Ohashi2018,
title = {Prognostic utility of atypical mitoses in patients with breast cancer: A comparative study with Ki67 and phosphohistone H3},
author = {Ryuji Ohashi and Shigeki Namimatsu and Takashi Sakatani and Zenya Naito and Hiroyuki Takei and Akira Shimizu},
url = {https://pubmed.ncbi.nlm.nih.gov/30098295/},
doi = {10.1002/jso.25152},
issn = {10969098},
year = {2018},
date = {2018-09-01},
journal = {Journal of Surgical Oncology},
volume = {118},
number = {3},
pages = {557--567},
publisher = {John Wiley and Sons Inc.},
abstract = {Background and Objectives: Emerging evidence suggests that the presence of atypical mitoses is associated with poor prognosis in some types of cancer, but its clinical significance remains uncertain. Here, we investigated the occurrence of atypical mitoses in breast cancers. Methods: Mitotic figures, including normal and atypical mitoses, were assessed in resected histological sections from 109 patients with invasive carcinoma of no special type (ICNST). Comparisons with clinicopathological features and biomarkers such as Ki67 and phosphohistone H3 (PHH3) were performed. Results: The total number of mitotic figures, including atypical mitoses, was higher in situ and invasive ductal carcinoma components than in normal ducts. Morphological characteristics of atypical mitoses included multipolar, lagged, ring, asymmetrical mitoses, and anaphase bridge. Patients with higher total mitoses and PHH3, and the presence of atypical mitoses showed reduced overall survival (OS), compared to those with lower total mitoses and PHH3, and without atypical mitoses (P = 0.03, 0.02, and textless0.001, respectively). In multivariate analysis, the presence of atypical mitoses alone attained significant correlation with shorter OS (P textless 0.001). Conclusions: Atypical mitoses in routinely resected specimens have a robust prognostic value for ICNST of the breast, but its clinical utility remains to be validated in a multicenter large material.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background and Objectives: Emerging evidence suggests that the presence of atypical mitoses is associated with poor prognosis in some types of cancer, but its clinical significance remains uncertain. Here, we investigated the occurrence of atypical mitoses in breast cancers. Methods: Mitotic figures, including normal and atypical mitoses, were assessed in resected histological sections from 109 patients with invasive carcinoma of no special type (ICNST). Comparisons with clinicopathological features and biomarkers such as Ki67 and phosphohistone H3 (PHH3) were performed. Results: The total number of mitotic figures, including atypical mitoses, was higher in situ and invasive ductal carcinoma components than in normal ducts. Morphological characteristics of atypical mitoses included multipolar, lagged, ring, asymmetrical mitoses, and anaphase bridge. Patients with higher total mitoses and PHH3, and the presence of atypical mitoses showed reduced overall survival (OS), compared to those with lower total mitoses and PHH3, and without atypical mitoses (P = 0.03, 0.02, and textless0.001, respectively). In multivariate analysis, the presence of atypical mitoses alone attained significant correlation with shorter OS (P textless 0.001). Conclusions: Atypical mitoses in routinely resected specimens have a robust prognostic value for ICNST of the breast, but its clinical utility remains to be validated in a multicenter large material.
2.
Ishino, Kousuke; Kudo, Mitsuhiro; Peng, Wei Xia; Kure, Shoko; Kawahara, Kiyoko; Teduka, Kiyoshi; Kawamoto, Yoko; Kitamura, Taeko; Fujii, Takenori; Yamamoto, Tetsushi; Wada, Ryuichi; Naito, Zenya
In: Biochemical and Biophysical Research Communications, vol. 501, no. 3, pp. 668–673, 2018, ISSN: 10902104.
@article{Ishino2018,
title = {2-Deoxy-D-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells},
author = {Kousuke Ishino and Mitsuhiro Kudo and Wei Xia Peng and Shoko Kure and Kiyoko Kawahara and Kiyoshi Teduka and Yoko Kawamoto and Taeko Kitamura and Takenori Fujii and Tetsushi Yamamoto and Ryuichi Wada and Zenya Naito},
url = {https://pubmed.ncbi.nlm.nih.gov/29753740/},
doi = {10.1016/j.bbrc.2018.05.041},
issn = {10902104},
year = {2018},
date = {2018-06-01},
journal = {Biochemical and Biophysical Research Communications},
volume = {501},
number = {3},
pages = {668--673},
publisher = {Elsevier B.V.},
abstract = {The glycolytic inhibitor 2-deoxy-D-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines. To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment. Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated. Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels. Therefore, we assessed the amounts of total N-glycoproteins. Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK). These data may shed light on HBP dysfunction. Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells. Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG. These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The glycolytic inhibitor 2-deoxy-D-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines. To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment. Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated. Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels. Therefore, we assessed the amounts of total N-glycoproteins. Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK). These data may shed light on HBP dysfunction. Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells. Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG. These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
3.
Arai, Hiroki; Wada, Ryuichi; Ishino, Kousuke; Kudo, Mitsuhiro; Uchida, Eiji; Naito, Zenya
Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis Journal Article
In: International Journal of Oncology, vol. 52, no. 3, pp. 978–988, 2018, ISSN: 17912423.
@article{Arai2018,
title = {Expression of DNA damage response proteins in gastric cancer: Comprehensive protein profiling and histological analysis},
author = {Hiroki Arai and Ryuichi Wada and Kousuke Ishino and Mitsuhiro Kudo and Eiji Uchida and Zenya Naito},
url = {https://pubmed.ncbi.nlm.nih.gov/29328366/},
doi = {10.3892/ijo.2018.4238},
issn = {17912423},
year = {2018},
date = {2018-03-01},
journal = {International Journal of Oncology},
volume = {52},
number = {3},
pages = {978--988},
publisher = {Spandidos Publications},
abstract = {Gastric cancer is the third major cause of cancerrelated mortality in Japan. The aim of this study was to identify a factor implicated in the biology of gastric cancer by comprehensive protein profiling. Protein profiling was carried out by liquid chromatography-tandem mass spectrometry, using formalin-fixed paraffin-embedded specimens of 17 gastric cancer cases. Pathway analysis and orthogonal partial least square-discriminant analysis suggested the significant expression of ribonucleoproteins, heterogeneous nuclear ribonucleoproteins, interleukin binding factor 2 (ILF2), KU70 and KU80, which are involved in DNA damage response (DDR). Thus, the expression and phosphorylation levels of KU70, ILF2, CHK1 and CHK2 were examined by immunohistochemistry in 42 cases of gastric cancer. The expressions of ILF2 and CHK1 were unaffected in all cases. The expression and phosphorylation of CHK2 were absent in 2 cases. Despite the expression of proteins, the phosphorylation of KU70 and CHK2 appeared to be impaired in 1 and 4 cases, respectively. In 7 out of 42 cases (17%), DDR appeared to be impaired. Recurrence was noted in 2 out of these 7 cases (29%), whereas the recurrence was noted in 2 out of the remaining 35 cases (6%). The expression levels of KU70, ILF2, CHK1, CHK2 and TP53 were further examined in 4 gastric cancer cell lines. The expression and phosphorylation levels following exposure to ultraviolet radiation were abnormal in the 3 cell lines. The normal consecutive phosphorylation of CHK1 and CHK2, the upregulation of TP53 and an increase in apoptotic cell death following exposure to ultraviolet radiation was detected only in one cell line, suggesting that the preserved functions of DDR and TP53 are necessary for the determination of cell fate. It is thus suggested that DDR plays an important role in the pathobiology of gastric cancers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gastric cancer is the third major cause of cancerrelated mortality in Japan. The aim of this study was to identify a factor implicated in the biology of gastric cancer by comprehensive protein profiling. Protein profiling was carried out by liquid chromatography-tandem mass spectrometry, using formalin-fixed paraffin-embedded specimens of 17 gastric cancer cases. Pathway analysis and orthogonal partial least square-discriminant analysis suggested the significant expression of ribonucleoproteins, heterogeneous nuclear ribonucleoproteins, interleukin binding factor 2 (ILF2), KU70 and KU80, which are involved in DNA damage response (DDR). Thus, the expression and phosphorylation levels of KU70, ILF2, CHK1 and CHK2 were examined by immunohistochemistry in 42 cases of gastric cancer. The expressions of ILF2 and CHK1 were unaffected in all cases. The expression and phosphorylation of CHK2 were absent in 2 cases. Despite the expression of proteins, the phosphorylation of KU70 and CHK2 appeared to be impaired in 1 and 4 cases, respectively. In 7 out of 42 cases (17%), DDR appeared to be impaired. Recurrence was noted in 2 out of these 7 cases (29%), whereas the recurrence was noted in 2 out of the remaining 35 cases (6%). The expression levels of KU70, ILF2, CHK1, CHK2 and TP53 were further examined in 4 gastric cancer cell lines. The expression and phosphorylation levels following exposure to ultraviolet radiation were abnormal in the 3 cell lines. The normal consecutive phosphorylation of CHK1 and CHK2, the upregulation of TP53 and an increase in apoptotic cell death following exposure to ultraviolet radiation was detected only in one cell line, suggesting that the preserved functions of DDR and TP53 are necessary for the determination of cell fate. It is thus suggested that DDR plays an important role in the pathobiology of gastric cancers.
4.
Kure, Shoko; Kudo, Mitsuhiro; Ishino, Kousuke; Wada, Ryuichi; Naito, Zenya
Nuclear Morphological Changes in Papillary Thyroid Carcinoma Cell: The Utility of a 3-Dimensional (3D) Holographic Microscopy in Cytology Journal Article
In: Journal of Cytology & Histology, vol. 09, no. 06, pp. 9–10, 2018, ISSN: 21577099.
@article{Kure2018,
title = {Nuclear Morphological Changes in Papillary Thyroid Carcinoma Cell: The Utility of a 3-Dimensional (3D) Holographic Microscopy in Cytology},
author = {Shoko Kure and Mitsuhiro Kudo and Kousuke Ishino and Ryuichi Wada and Zenya Naito},
url = {https://www.omicsonline.org/open-access/nuclear-morphological-changes-in-papillary-thyroid-carcinoma-cell-the-utility-of-a-3dimensional-3d-holographic-microscopy-in-cytol-2157-7099-1000527-106659.html},
doi = {10.4172/2157-7099.1000527},
issn = {21577099},
year = {2018},
date = {2018-01-01},
journal = {Journal of Cytology & Histology},
volume = {09},
number = {06},
pages = {9--10},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
| 1. | Tomori, Yuji; Ohashi, Ryuji; Sawaizumi, Takuya; Naito, Zenya; Nanno, Mitsuhiko; Takai, Shinro Intramuscular Epithelioid Sarcoma Presenting as Extrinsic Flexor Tightness in the Forearm Journal Article In: Journal of Hand Surgery, vol. 43, no. 10, pp. 954.e1–954.e5, 2018, ISSN: 15316564. @article{Tomori2018,Epithelioid sarcoma is an uncommon soft tissue sarcoma involving predominantly the distal extremities of adolescents and young adults. Its rarity makes it difficult to diagnose accurately and treat properly in the early stages. We discuss the delayed diagnosis of a 37-year-old man who presented with extrinsic flexor tightness of the wrist and fingers. We initially thought that the lesion resulted from inflamed soft tissue of the flexor muscles causing contracture. However, histological examination of a biopsy specimen revealed nodular proliferation of epithelioid and spindle cells, which were immunoreactive to epithelial and nonepithelial markers, respectively, leading to the final diagnosis of epithelioid sarcoma. |
| 2. | Tomori, Yuji; Motoda, Norio; Ohashi, Ryuji; Sawaizumi, Takuya; Nanno, Mitsuhiko; Takai, Shinro Preiser disease after repeated local glucocorticoid injections: A case report Journal Article In: Medicine (United States), vol. 97, no. 38, 2018, ISSN: 15365964. @article{Tomori2018a,Rationale: Preiser disease or avascular necrosis (AVN) of the scaphoid causes intolerable wrist pain and malalignment of the carpal bones. In previously reported cases, patients have had a history of steroid use for systemic illness such as autoimmune hemolytic anemia, systemic lupus erythematosus, or renal transplantation, or have had other risk factors, such as smoking, alcoholism, or infection. In particular, systemic glucocorticoid therapy has been most commonly associated with the disease. Although there are reports of AVN of the scaphoid induced by systemic glucocorticoids, no prior report has associated AVN of the carpal bones with repeated local injections of glucocorticoids. Patient concerns: We present a case in which it was strongly suspected that AVN of the scaphoid was induced by repeated local glucocorticoid injections. The patient had no history of excessive alcohol use, smoking, or trauma, except for local repeated steroid injections. Diagnoses: Initially, she had diagnosed with de Quervain's disease and was treated by repeated local glucocorticoid injections followed by surgery for de Quervain's disease. Five years after surgery for de Quervain's disease, the patient presented at our hospital with sudden onset of intolerable pain in her right wrist without a history of trauma. In spite of nonsurgical treatment with rest, immobilization, analgesia, and surgery, her wrist pain was not improved. After further repeated local steroid injections in her wrist, radiographs, and magnetic resonance imaging of her wrist showed the AVN of the scaphoid. Interventions: Surgery was performed and the fragmented proximal scaphoid and the entire lunate were resected. Outcomes: The diagnosis was confirmed according to the histopathological examination of the proximal scaphoid bone, which showed the characteristic of AVN of the scaphoid. At follow-up evaluation, radiographs of the right wrist showed no progression of osteoarthritis. The patient had no tenderness or residual pain at the wrist and had no desire to pursue additional surgery. Lessons: We have presented a case with AVN of the scaphoid, which was strongly suspected to be associated with the repeated local steroid injections. Further studies are required to more fully elucidate the association between AVN of the scaphoid and repeated local steroid injections. |
| 3. | Okabe, Masahiro; Takamura, Tsuyoshi; Tajiri, Akiko; Tsuboi, Nobuo; Ishikawa, Masahiro; Ogura, Makoto; Ohashi, Ryuji; Oda, Takashi; Yokoo, Takashi A case of infection-related glomerulonephritis with massive eosinophilic infiltration Journal Article In: Clinical Nephrology, vol. 90, no. 2, pp. 142–147, 2018, ISSN: 03010430. @article{Okabe2018,Infection-related glomerulonephritis (IRGN) is rarely complicated with eosinophil infiltration into the glomerulus. Here we report a case of eosinophilic proliferative glomerulonephritis related with infection. A 70-year-old man with respiratory symptoms displayed hypereosinophilia, hypocomplementemia, impaired renal function, and nephrotic syndrome. Renal biopsy revealed endocapillary proliferative glomerulonephritis with immunostaining for immunoglobulin G and complement 3, and subepithelial hump-like electron-dense deposits, thus fulfilling the criteria for IRGN. Immunostaining for the nephritis-associated plasmin receptor (NAPlr) in the glomerulus confirmed the diagnosis of IRGN. Of note, eosinophils infiltrated into the glomerular subendothelial spaces, renal tubules, peritubular capillaries, and the interstitium in the kidney as well as in the alveolar walls and pulmonary arteries in the lung. Corticosteroid therapy rapidly improved hypereosinophilia as well as respiratory symptoms and renal function. Urinary protein exertion was decreased, and serum level of complement and albumin was increased. These findings suggest that eosinophil infiltration might play a prominent role in respiratory and renal disorders. Severe endothelial damage of glomeruli and tubulointerstitial nephritis, caused by eosinophil-rich inflammation, might significantly contribute to exacerbation of renal insufficiency. |
| 4. | Endo, Yoko; Ohashi, Ryuji; Inai, Shunta; Yokoshima, Kazuhiko; Nakamizo, Munenaga; Shimizu, Akira; Okubo, Kimihiro; Naito, Zenya Carcinosarcoma ex pleomorphic adenoma of the submandibular gland in a 64-year-old man: A case report Journal Article In: Journal of Nippon Medical School, vol. 85, no. 1, pp. 51–55, 2018, ISSN: 13473409. @article{Endo2018,Carcinosarcoma (CS) is a rare tumor, consisting of both carcinomatous and sarcomatous components. In this paper, we present a case of CS arising from a pleomorphic adenoma (PA) of the submandibular gland. A 64-year-old Japanese man presented with a left submandibular mass that had developed for 20 years with complaints of pain for the last 3 months. Magnetic resonance imaging showed a lesion involving the left submandibular gland. The patient underwent total dissection of the left submandibular gland and left cervical lymph nodes. Upon gross examination, the mass appeared completely covered by fibroadipose tissue measuring 46×42×45 mm; sectioning revealed a solid-white nodule with central bleeding and necrosis, invading into the surrounding adipose tissue. Microscopically, the presence of carcinomatous and sarcomatous components in the fibro-myxomatous stroma was detected, suggestive of pre-existing PA. The carcinoma component was diagnostic of salivary adenocarcinoma, not otherwise specified, whereas the sarcomatous component exhibited features of osteosarcoma characterized by formation of osteoid. As the border between the carcinomatous and sarcomatous components was not evident, CS may have occurred via transformation of the carcinoma into sarcoma. Tumor metastasis was detected in the cervical lymph nodes. Immunohistochemically, AE1/AE3 expression was noted in the carcinomatous component, but not in the osteosarcoma component. Both components were diffusely positive for vimentin. Four months after the operation, the patient developed a metastatic CS lesion in the lung, suggesting tumor aggression. |
| 1. | Ohashi, Ryuji; Hayama, Ayako; Matsubara, Miyuki; Watarai, Yasuhiko; Sakatani, Takashi; Naito, Zenya; Shimizu, Akira Breast carcinoma with osteoclast-like giant cells: A cytological-pathological correlation with a literature review Journal Article In: Annals of Diagnostic Pathology, vol. 33, pp. 1–5, 2018, ISSN: 15328198. @article{Ohashi2018a,Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease characterized by the infiltration of OGCs in the tumor; however, cytological aspects of this tumor type remain elusive. We examined the cytological features in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were histologically diagnosed with breast carcinoma with OGCs. We compared FNA and clinicopathological findings with results from the published literature. Histological assessment of the resected samples showed that all tumors exhibited a histological grade 1 phenotype with a predominant cribriform architecture. Four patients were estrogen receptor positive, and 1 patient showed a triple negative phenotype. All patients survived without tumor recurrence. In the FNA smears, tumor cells were arranged in loosely cohesive clusters, characterized by varying degrees of OGCs infiltration and rare formation of solid tumor nests. Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied by OGCs at the peripheral regions. In all patients, tumor cells were small without severe nuclear atypia. None of the patients showed significant background necrosis. In summary, cytological features of breast carcinoma with OGCs are characterized by loose aggregates of low grade tumor cells, the presence of OGCs, and the absence of necrosis, all of which were consistent with features reported previously. This peculiar form of breast tumors should be included in the differential diagnosis, when physicians encounter FNA findings including low grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs. |
| 2. | Ohashi, Ryuji; Yanagihara, Keiko; Namimatsu, Shigeki; Sakatani, Takashi; Takei, Hiroyuki; Naito, Zenya; Shimizu, Akira Osteoclast-like giant cells in invasive breast cancer predominantly possess M2-macrophage phenotype Journal Article In: Pathology Research and Practice, vol. 214, no. 2, pp. 253–258, 2018, ISSN: 16180631. @article{Ohashi2018b,Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare tumor; however, their clinicopathological aspects remain unclear. We described the clinicopathological characteristics of 8 patients with breast carcinoma with OGCs. Immuno-phenotypes of the OGCs were comparatively examined with that of foreign body giant cells (FBGCs) in 4 cases of granulomatous reaction (GR) without cancerous elements. In most cancers, tumors displayed cribriform and tubular growth patterns. Three cases showed moderate to high nuclear grade, while all the other tumors had low nuclear grade. Six patients were estrogen receptor (ER) positive, while triple negative phenotype was identified in 2 patients. During the follow-up period, 1 patient had local recurrence of the tumor, and all the patients remained alive. All OGCs and FBGCs expressed CD68, a pan-macrophage marker. OGCs in all the breast cancers showed moderate to high expression of CD163 — a marker of M2-macrophage with pro-tumoral function — whereas its expression in FBGCs was low to moderate (p = 0.04). CD86 — a marker of M1-macrophage with a tumoricidal activity — was positive in the OGCs of 3 breast cancers, and in the FBGCs of 3 GR cases (p = 0.15). The expression of CD163 was significantly higher than that of CD86 in the OGCs of breast cancer (p textless 0.001), whereas they were comparable in the FBGCs of GR (p = 0.79). In summary, we found that breast carcinoma with OGCs mostly exhibited cribriform and tubular growth pattern, ER positivity, and predominantly possessed the M2-macrophage phenotype. However, the clinical significance of OGCs in breast cancer needs to be elucidated in further studies involving a larger number of cases. |
| 1. | Ohashi, Ryuji; Sangen, Maoka; Namimatsu, Shigeki; Takei, Hiroyuki; Naito, Zenya IMP3 contributes to poor prognosis of patients with metaplastic breast carcinoma: A clinicopathological study Journal Article In: Annals of Diagnostic Pathology, vol. 31, pp. 30–35, 2017, ISSN: 15328198. @article{Ohashi2017a,Metaplastic breast carcinoma (MBC) is a rare type of tumor with heterogenous histological patterns. We investigated the immunohistochemical expression of IMP3, an oncofetal protein, in 31 MBC patients in association with histological subtypes and clinical outcomes. The cohort consisted of spindle cell carcinoma (SPC) (n = 11), squamous cell carcinoma (SCC) (n = 14), matrix-producing carcinoma (MPC) (n = 4), carcinoma with osteocartilaginous elements (COC) (n = 1), and low grade adenosquamous cell carcinoma (ASC) (n = 1). IMP3 expression was identified in 7 cases of SPC (64%) and 6 patients of all the other subtypes (p = 0.051). In comparison between IMP3 high (n = 13) and low (n = 18) groups, a large-sized tumor (≥ 4.0 cm) was identified in 9 IMP3 high patients, and 14 IMP3 low patients had a small-sized tumor (p = 0.01). High Ki67 positivity was detected in all of the IMP3 high patients and in 7 of the IMP3 low patients (p = 0.002). During the follow-up period, 9 IMP3 high patients died, whereas 15 of the 18 IMP3 low patients remained alive (p = 0.004). A univariate analysis revealed that IMP3 expression and tumor size were significantly associated with poor clinical outcomes (p = 0.03 and textless 0.001, respectively). The IMP3 high group was likely to be associated with reduced overall survival compared to the IMP3 low group (p = 0.06). These findings indicate that IMP3 may contribute to the aggressive behavior of MBC, and that this expression could potentially be a prognostic marker of MBC. |
| 2. | Matsumoto, Noriko M; Peng, Wei Xia; Aoki, Masayo; Akaishi, Satoshi; Ohashi, Ryuji; Ogawa, Rei; Naito, Zenya In: International Wound Journal, vol. 14, no. 6, pp. 1088–1093, 2017, ISSN: 1742481X. @article{Matsumoto2017a,Keloids grow and do not regress. They are characterised histologically by hyalinised keloidal collagen (HKC). HKC amounts vary, and the mechanism by which they form is unclear. To clarify how HKCs form and whether their formation associates with specific clinical features, we studied the histological findings of earlobe keloids and compared them with respective clinical features. A total of 50 earlobe keloids from 43 patients were used for histological analysis of keloid size (mm2), HKC area (mm2) and HKC area ratio (%). As a result, keloid durations ranged from 3 months to textgreater13 years. Early-stage keloids exhibited little HKC and a tendency for the HKCs to locate in perivascular regions. In later-stage keloids, the HKCs were extremely interconnected and formed a thick bitten donut-shaped region. HKC area ratios correlated positively with keloid duration (r2 = 0textperiodcentered58, Ptextless0textperiodcentered05). HKC area ratios and keloid durations did not correlate with keloid sizes. These patterns of HKC formation and growth may explain why local therapies, which effectively remove fibroblasts and accumulated collagen but not HKCs, are ineffective in older keloids. Keloids should be promptly treated after diagnosis, and older keloids with extensive HKCs may require surgical excision followed by radiotherapy. |
| 3. | Ohashi, Ryuji; Fukazawa, Ryuji; Watanabe, Makoto; Hashimoto, Koji; Suzuki, Nobuko; Nagi-Miura, Noriko; Ohno, Naohito; Shimizu, Akira; Itoh, Yasuhiko Characterization of a murine model with arteritis induced by Nod1 ligand, FK565: A comparative study with a CAWS-induced model Journal Article In: Modern Rheumatology, vol. 27, no. 6, pp. 1024–1030, 2017, ISSN: 14397609. @article{Ohashi2017e,Objective: Kawasaki disease (KD) occurs via activation of the innate immune system. Nucleotide oligomerization domain-1 (NOD1) is a pattern recognition receptor regulating the innate immunity. We characterized histopathology of arteritis induced by FK565, a ligand for NOD1, in mice, compared with Candida albicans water-soluble fraction (CAWS)-induced model. Methods: Vasculitis was induced by injection of FK565 or CAWS into C57BL6/J mice (n = 9 and n = 11, respectively). At 4 weeks, they were sacrificed, and plasma cytokines and chemokines were measured. Results: FK565 injection induced vasculitis mainly involving bilateral coronary arteries whereas the aortic root was diffusely affected in CAWS mice. In FK565 animals, the abdominal aorta and its branching arteries also exhibited inflammation with atherosclerosis. IL-1$alpha$, IL-1$beta$, IL-5 and RANTES were increased in FK565 group whereas IL-6, IL-13, G-CSF, IFN-$gamma$, and TNF-$alpha$ were higher in CAWS animals (p textless.05 for all variables). The total area of inflammation in FK565 mice appeared to correlate with IL-1$beta$ levels (r = 0.71 |
| 4. | Ohashi, Ryuji; Sangen, Maoka; Namimatsu, Shigeki; Yanagihara, Keiko; Yamashita, Koji; Sakatani, Takashi; Takei, Hiroyuki; Naito, Zenya Prognostic value of IMP3 expression as a determinant of chemosensitivity in triple-negative breast cancer Journal Article In: Pathology Research and Practice, vol. 213, no. 9, pp. 1160–1165, 2017, ISSN: 16180631. @article{Ohashi2017c,Triple negative breast cancer (TNBC) has an aggressive phenotype and poor prognosis. Neoadjuvant chemotherapy (NAC) is often used to treat TNBC, but some patients are resistant to NAC. We postulated that a subpopulation of TNBC cells expressing IMP3, an oncofetal protein, could be resistant to NAC, contributing to the poor prognosis. We investigated immunohistochemical expression of IMP3 in 42 TNBC patients who underwent NAC in association with clinical outcomes. The patients were divided into IMP3 positive (+) (n = 19) and negative (−) (n = 23) groups. High Ki67 positivity was detected in 13 patients of the IMP3 + group and 8 cases in the IMP3 – group (p = 0.03). While 9 patients in the IMP3 – group (39%) were responders, the majority of the IMP3 + patients (84.2%) were non-responders (p = 0.01). In a Cox proportional hazard model, IMP3 expression was independently associated with poor NAC response and clinical outcomes (p = 0.03 and 0.046, respectively). The IMP3 + group showed a tendency toward shorter overall survival compared to the IMP3 – group with marginal significance (p = 0.07). These findings suggest that IMP3 + tumor cells contributed to the poor clinical outcomes by exerting a chemoresistance to NAC, and that IMP3 expression has prognostic value as a biomarker for chemosensitivity and overall survival in TNBC. |
| 5. | Ohashi, Ryuji; Kawahara, Kiyoko; Namimatsu, Shigeki; Okamura, Ritsuko; Igarashi, Takehito; Sugitani, Iwao; Naito, Zenya Expression of MRP1 and ABCG2 is associated with adverse clinical outcomes of papillary thyroid carcinoma with a solid component Journal Article In: Human Pathology, vol. 67, pp. 11–17, 2017, ISSN: 15328392. @article{Ohashi2017d,Solid variant of papillary thyroid carcinoma (PTC) is characterized by a solid component (SC) retaining classical cytological features of PTC. Despite some controversies, PTC with SC (PTCSC) cases have poor prognosis compared with well-differentiated PTC. We investigated if cancer stem cells (CSCs) may have a role in pathogenesis of PTCSC. PTCSC tumors (n = 27) were histologically represented by a mixture of papillary component (PC) and varying degrees of SC involving 10% to 85% of the tumor. Immunohistochemical expression of CSC markers ABCG2 and MRP1, and HBME1 and CK19 was compared between SC and PC within each tumor in association with clinicopathological parameters. ABCG2 and MRP1 were highly expressed in SC, whereas their expression was limited or absent in PC (P =.04 and.002, respectively). In contrast, expression of HBME1 and CK19 appeared higher in PC than in SC (P =.08 and.02, respectively). Higher expression of ABCG2 was associated with higher incidence of large-sized SC (P =.01). Higher expression of MRP1 was associated with higher incidence of lymphovascular invasion (P =.049). Higher expression of ABCG2 and MRP1, and lower expression of CK19 in SC were associated with higher tumor recurrence rate (P =.02,.01, and.02, respectively), and shorter disease-free survival (P textless.001 for all the variables). Our findings indicate that the tumor cells harboring CSC-like characteristics in SC could contribute to the pathogenesis of PTCSC and might account for the poor disease prognosis. |
| 6. | Ohashi, Ryuji; Murase, Yukihiro; Matsubara, Miyuki; Watarai, Yasuhiko; Igarashi, Takehito; Sugitani, Iwao; Naito, Zenya Fine needle aspiration cytology of the papillary thyroid carcinoma with a solid component: A cytological and clinical correlation Journal Article In: Diagnostic Cytopathology, vol. 45, no. 5, pp. 391–398, 2017, ISSN: 10970339. @article{Ohashi2017f,Background: Solid variant of papillary thyroid carcinoma is a rare subtype of papillary thyroid carcinoma (PTC) containing a solid component (SC), and thus its cytological and clinicopathological features remain elusive. We examined fine needle aspiration (FNA) cytological features of PTC with variable degrees of SC (20-80% of the tumor)(PTCSC) in comparison to well-differentiated PTC (WPTC). Methods: Twenty-six cases of PTCSC were histologically stratified into major-SC (SC textgreater50% of the tumor) and minor-SC (textless49%) groups. Pre-operative FNA smears were compared between major-SC (n = 11) and minor-SC (n = 15) groups, and between PTCSC and WPTC (n = 39) groups. Results: In FNA smears of PTCSC, the presence of cohesive solid nests, trabecular patterns, overlapping, enlarged nuclei, pleomorphism, and distinct nucleolus, and the absence of colloid and psammoma bodies were noted more often than in WPTC, while classical cytological features of PTC, such as nuclear grooves and/or pseudo-nuclear inclusions, were preserved. There was no significant difference in FNA findings between the major-SC and minor-SC groups. The presence of either solid nests or trabecular patterns, and overlapping in FNA smears of PTCSC was associated with a higher recurrence rate of the tumor (P = 0.007 and P textless 0.001, respectively). Conclusion: PTCSC may pre-operatively be identified by detecting its characteristic cytological features in FNA smears, regardless of the proportion of SC within the tumor. Because clinical outcomes of PTCSC remain undetermined, it is imperative to postulate PTCSC as a differential diagnosis, even when classical nuclear features of PTC are present. Diagn. Cytopathol. 2017;45:391–398. textcopyright 2017 Wiley Periodicals, Inc. |
| 7. | Ohashi, Ryuji; Kawahara, Kiyoko; Namimatsu, Shigeki; Igarashi, Takehito; Sakatani, Takashi; Sugitani, Iwao; Naito, Zenya Clinicopathological significance of a solid component in papillary thyroid carcinoma Journal Article In: Histopathology, vol. 70, no. 5, pp. 775–781, 2017, ISSN: 13652559. @article{Ohashi2017,Aims: Solid variant of papillary thyroid carcinoma (SVPTC) is characterized by a solid component (SC) involving more than 50% of the tumour with the preservation of the classical cytological features of papillary thyroid carcinoma (PTC). However, the clinical significance of SC in PTC has been rarely examined. Herein, we investigated retrospectively the clinicopathological features of PTC with various degrees (10–85%) of SC (PTCSC). Methods and results: Patients with PTCSC (n = 27) were stratified into SC-major (SC textgreater 50% of the tumour) and SC-minor (SC textless 49%) groups. The clinicopathological parameters were compared to the well-differentiated PTC (WPTC) group (n = 47). Both SC-minor (n = 18) and SC-major (n = 9) groups had increased incidence of a large-sized tumour, extracapsular extension and a high recurrence rate, compared to WPTC. Disease-free survival (DFS) of both SC-minor and SC-major was shorter than that of WPTC (P = 0.035 and P = 0.016, respectively). Overall survival was similar among all the groups. Univariate analysis revealed that SC was associated significantly with a recurrence rate (P = 0.018). Using multivariate analysis, SC appeared to be associated with a recurrence rate with borderline significance (P = 0.055). Conclusions: Our findings indicate that the presence of SC in PTC, regardless of the proportion, is associated with adverse clinical parameters and a shorter DFS. |
| 8. | Ohashi, R; Matsubara, M; Watarai, Y; Yanagihara, K; Yamashita, K; Tsuchiya, S I; Takei, H; Naito, Z Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants Journal Article In: Cytopathology, vol. 28, no. 2, pp. 122–130, 2017, ISSN: 13652303. @article{Ohashi2017b,Objective: Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. Methods: We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. Results:: Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P textless 0.001 |
| 9. | Matsumoto, Noriko M; Aoki, Masayo; Nakao, Junichi; Peng, Wei Xia; Takami, Yoshihiro; Umezawa, Hiroki; Akaishi, Satoshi; Ohashi, Ryuji; Naito, Zenya; Ogawa, Rei In: Plastic and Reconstructive Surgery, vol. 139, no. 1, pp. 79e–84e, 2017, ISSN: 00321052. @article{Matsumoto2017,Background: The commonly used flap models have drawbacks that limit their usefulness. In the random skin flap model, flap necrosis is caused by both arterial and venous insufficiency. In the axial skin flap model, flap viability is easily affected by the pedicle blood flow and can result in complete necrosis. This study aimed to establish a new rat skin flap model that has a consistent flap survival rate and in which venous congestion and arterial ischemia can be readily distinguished macroscopically. Methods: Rats underwent reverse U-shaped bipedicled superficial epigastric artery flap elevation. The right superficial epigastric vessels formed the pedicle. In the control rats (n = 3), the left superficial epigastric vessels were left intact. In the ischemia group (n = 10), the left superficial epigastric artery was ligated. In the congestion group (n = 10), the left superficial epigastric vein was ligated. The flap was returned to the original site and sutured. The surrounding neovascularization was blocked by polyurethane film. Flap survival rates were evaluated on postoperative day 3. Results: The flaps in the ischemia and congestion groups were noticeably pale and violet, respectively. Flap necrosis was noted in the contralateral distal zone only. It started on postoperative day 2 in the ischemia and congestion groups. The mean flap survival rates of the control, ischemia, and congestion groups were 100 percent, 61.8 percent (range, 56.9 to 67.1 percent), and 42.3 percent (35.7 to 48.7 percent), respectively (all p textless 0.001). Conclusions: The flap facilitated discrimination of the effects of ischemia and congestion. This new rat skin flap model is simple and easy to construct, and has a consistent flap survival rate. |
| 1. | Ito, Naoko; Ohashi, Ryuji; Nagata, Michio C3 glomerulopathy and current dilemmas Journal Article In: Clinical and Experimental Nephrology, vol. 21, no. 4, pp. 541–551, 2017, ISSN: 14377799. @article{Ito2017,C3 glomerulopathy (C3G) is a recently identified disease entity caused by dysregulation of the alternative complement pathway, and dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory detection of complement dysregulation is still uncommon in practice, “dominant C3 deposition by two orders greater than that of immunoglobulins in the glomeruli by immunofluorescence”, as stated in the consensus report, defines C3G. However, this morphological definition possibly includes the cases with glomerular diseases of different mechanisms such as post-infectious glomerulonephritis. In addition, the differential diagnosis between DDD and C3GN is often difficult because the distinction between these two diseases is based solely on electron microscopic features. Recent molecular and genetic advances provide information to characterize C3G. Some C3G cases are found with genetic abnormalities in complement regulatory factors, but majority of cases seem to be associated with acquired factors that dysregulate the alternative complement pathway. Because clinical courses and prognoses among glomerular diseases with dominant C3 deposition differ, further understanding the background mechanism, particularly complement dysregulation in C3G, is needed. This may resolve current dilemmas in practice and shed light on novel targeted therapies to remedy the dysregulated alternative complement pathway in C3G. |
| 1. | Takata, Hideyuki; Kudo, Mitsuhiro; Yamamoto, Tetsushi; Ueda, Junji; Ishino, Kousuke; Peng, Wei Xia; Wada, Ryuichi; Taniai, Nobuhiko; Yoshida, Hiroshi; Uchida, Eiji; Naito, Zenya Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma Journal Article In: Oncology Letters, vol. 12, no. 6, pp. 4896–4904, 2016, ISSN: 17921082. @article{Takata2016,The prognosis of hepatocellular carcinoma (HCC) is unfavorable following complete tumor resection. The aim of the present study was to identify a molecule able to predict HCC prognosis through comprehensive protein profiling and to elucidate its clinicopathological significance. Comprehensive protein profiling of HCC was performed by liquid chromatography–tandem mass spectrometry. Through the bioinformatic analysis of proteins expressed differentially in HCC and non–HCC tissues, protein disulfide–isomerase A3 (PDIA3) was identified as a candidate for the prediction of prognosis. PDIA3 expression was subsequently examined in 86 cases of HCC by immunostaining and associations between PDIA3 expression levels and clinicopathological characteristics were evaluated. The Ki–67 index and apoptotic cell death of carcinoma cells were examined by immunostaining and terminal deoxynucleotidyl transferase dUTP nick–end labeling assay in 24 cases. The results demonstrated that PDIA3 was expressed in all 86 HCC cases; 56 HCC cases (65%) exhibited high expression of PDIA3 and 30 (35%) exhibited low expression. The disease–free and overall survival times of HCC patients with high PDIA3 expression were significantly shorter than in HCC patients with low expression. Furthermore, increased expression of PDIA3 was associated with an elevated Ki–67 index, indicating increased cancer cell proliferation and a reduction in apoptotic cell death. Taken together, these results suggest that PDIA3 expression is associated with tumor proliferation and decreased apoptosis in HCC, and that increased expression of PDIA3 predicts poor prognosis. PDIA3 may therefore be a key molecule in the development of novel targeting therapies for patients with HCC. |
| 2. | Wada, Ryuichi; Yagihashi, Soroku; Naito, Zenya mRNA expression of delta-HER2 and its clinicopathological correlation in HER2-overexpressing breast cancer Journal Article In: Molecular Medicine Reports, vol. 14, no. 6, pp. 5104–5110, 2016, ISSN: 17913004. @article{Wada2016a,Delta-human epidermal growth factor receptor 2 (HER2) is a splice variant of HER2, which lacks 16 amino acids in the extracellular domain. The aim of the present study was to elucidate the expression of delta-HER2 and its clinicopathological correlation in Japanese patients with HER2-overexpressing breast cancer. A total of 40 cases of HER2-overexpressing breast cancer were investigated. The mRNA expression levels of wild type (wt)-HER2 and delta-HER2 were quantitated by quantitative polymerase chain reaction using RNA extracted from formalin-fixed paraffin-embedded specimens. In addition, the activated form of phosphorylated-SRC (pSRC) and Ki-67 were detected by immunostaining. The mRNA expression levels of wt-HER2 varied largely, and the mRNA levels of delta-HER2 were correlated with those of wt-HER2. Furthermore, the enhanced immunostaining of pSRC was detected in 15 cases. Unsupervised hierarchal clustering of wt-HER2, delta-HER2 and pSRC was used to separate the cases into three clusters. In the first cluster, the levels of wt-HER2 and delta-HER2 were low, and pSRC immunostaining was low. Two other clusters were characterized by moderately and highly increased levels of wt-HER2 and delta-HER2 mRNA expression and enhanced pSRC. The delta/wt ratio was higher in the first cluster. Positive lymph node status and recurrence were more frequent in the first cluster compared with those in the two other clusters. Furthermore, the delta/wt ratio was significantly increased in lymph node-positive and recurrent cases, compared with in lymph node-negative and non-recurrent cases. The present study demonstrated that delta-HER2 was expressed in Japanese patients with HER2-overexpressing breast cancer. High mRNA expression levels of delta-HER2 were associated with pSRC and increased proliferation of tumor cells. A poor prognosis may be predicted by the increase in delta/wt ratio in HER2-overexpressing breast cancer. |
| 3. | Ohashi, Ryuji; Hayama, Ayako; Yanagihara, Keiko; Yamashita, Koji; Sakatani, Takashi; Takei, Hiroyuki; Naito, Zenya Prognostic significance of mucin expression profiles in breast carcinoma with signet ring cells: A clinicopathological study Journal Article In: Diagnostic Pathology, vol. 11, no. 1, 2016, ISSN: 17461596. @article{Ohashi2016c,Background: Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma; however, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of SRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing SRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6. Methods: Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied. Each case was categorized as high (textgreater31%) or low (textless30%) SRC tumor. The SRCs were morphologically classified into the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4, MUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1 was categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous accentuation (CM) type. These histological findings were compared with other clinicopathological parameters. Results: The series consisted of invasive ductal carcinoma (n=9), invasive lobular carcinoma (n=9), and mucinous carcinoma (n=4) cases. The SRC population accounted for 8-81% of the tumor cells. Eight cases had ICL type SRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n=12) and low (n=10) percentage of SRCs, nor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n=11), larger tumors, higher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified compared to the high MUC1 group (n=11; p=0.01 |
| 4. | Yamamoto, Tetsushi; Kudo, Mitsuhiro; Peng, Wei Xia; Takata, Hideyuki; Takakura, Hideki; Teduka, Kiyoshi; Fujii, Takenori; Mitamura, Kuniko; Taga, Atsushi; Uchida, Eiji; Naito, Zenya In: Tumor Biology, vol. 37, no. 10, pp. 13595–13606, 2016, ISSN: 14230380. @article{Yamamoto2016,Colorectal cancer (CRC) is one of the most common cancers worldwide, and many patients are already at an advanced stage when they are diagnosed. Therefore, novel biomarkers for early detection of colorectal cancer are required. In this study, we performed a global shotgun proteomic analysis using formalin-fixed and paraffin-embedded (FFPE) CRC tissue. We identified 84 candidate proteins whose expression levels were differentially expressed in cancer and non-cancer regions. A label-free semiquantitative method based on spectral counting and gene ontology (GO) analysis led to a total of 21 candidate proteins that could potentially be detected in blood. Validation studies revealed cyclophilin A, annexin A2, and aldolase A mRNA and protein expression levels were significantly higher in cancer regions than in non-cancer regions. Moreover, an in vitro study showed that secretion of aldolase A into the culture medium was clearly suppressed in CRC cells compared to normal colon epithelium. These findings suggest that decreased aldolase A in blood may be a novel biomarker for the early detection of CRC. |
| 5. | Ohashi, Ryuji; Matsubara, Miyuki; Watarai, Yasuhiko; Yanagihara, Keiko; Yamashita, Koji; ichi Tsuchiya, Shin; Takei, Hiroyuki; Naito, Zenya Diagnostic value of fine needle aspiration and core needle biopsy in special types of breast cancer Journal Article In: Breast Cancer, vol. 23, no. 4, pp. 675–683, 2016, ISSN: 18804233. @article{Ohashi2016,Background: Although fine needle aspiration (FNA) biopsy is an established tool to assess breast lesions, there has been a trend toward using core needle biopsy (CNB) instead. The aim of this study was to compare the diagnostic accuracy of FNA and CNB in special types of breast cancer. Methods: A retrospective review of diagnostic results of pre-operatively performed FNA or CNB, or a combination of the two, was conducted. The cases include histologically proven invasive ductal carcinoma of no special type (NST n = 159), invasive lobular carcinoma (ILC n = 65), mucinous carcinoma (MUC n = 51), and apocrine carcinoma (APO n = 25). Results: The absolute diagnostic sensitivity of FNA to detect malignancy in ILC and APO patients was inferior to that of NST patients (p textless 0.001 for ILC and APO). Within each cancer type, the sensitivity of CNB was higher than that of FNA in the ILC and APO patients (p textless 0.001 and p textless 0.05, respectively). As for NST and MUC patients, FNA and CNB had equivalent sensitivity. The sensitivity of FNA alone significantly improved when combined with CNB in NST, ILC and APO patients (p textless 0.05, p textless 0.001, and p textless 0.05, respectively). Conclusions: Our results suggest that FNA has less diagnostic accuracy than CNB for ILC and APO; thus, the use of CNB should be encouraged when these types of cancer are clinically suspected or when the initial FNA is inconclusive. |
| 6. | Ohashi, R; Sakatani, T; Matsubara, M; Watarai, Y; Yanagihara, K; Yamashita, K; Tsuchiya, S; Takei, H; Naito, Z Mucinous carcinoma of the breast: A comparative study on cytohistological findings associated with neuroendocrine differentiation Journal Article In: Cytopathology, vol. 27, no. 3, pp. 193–200, 2016, ISSN: 13652303. @article{Ohashi2016d,Objective: Mucinous carcinoma (MCA) may show neuroendocrine differentiation (ND), but the cytological features characteristic of ND remains elusive. We compared fine needle aspiration (FNA) findings of MCA between cases with high and low degrees of ND. Methods: Histological sections of 37 MCA cases were immunohistochemically evaluated for expression of chromogranin A and synaptophysin, and were graded as 0 to 3+ degrees of ND. They were divided into low ND (grade 0 and 1+) and high ND (grade 2+ and 3+) groups. Pre-operative FNA samples of each group were assessed for cytological features. Results: The mean age of the high ND group (n = 18) was higher than the low ND group (n = 19 |
| 7. | Kanzaki, Akiko; Kudo, Mitsuhiro; Ansai, Shin Ichi; Peng, Wei Xia; Ishino, Kousuke; Yamamoto, Tetsushi; Wada, Ryuichi; Fujii, Takenori; Teduka, Kiyoshi; Kawahara, Kiyoko; Kawamoto, Yoko; Kitamura, Taeko; Kawana, Seiji; Saeki, Hidehisa; Naito, Zenya Insulin-like growth factor 2 mRNA-binding protein-3 as a marker for distinguishing between cutaneous squamous cell carcinoma and keratoacanthoma Journal Article In: International Journal of Oncology, vol. 48, no. 3, pp. 1007–1015, 2016, ISSN: 17912423. @article{Kanzaki2016,In the histopathological diagnosis of cutaneous tumors, the differential diagnosis of squamous cell carcinoma (SCC) with crateriform architecture and keratoacanthoma (KA) is often difficult so an accurate understanding of the biological features and the identification of reliable markers of SCC and KA are crucial issues. Insulin-like growth factor 2 mRNA-binding protein-3 (IGF2BP3, also known as IMP3) is thought of as a bona fide oncofetal protein, which is overexpressed and is involved in cell proliferation, migration, and invasion in several kinds of tumors. However, the role of IMP3 in cutaneous SCC and KA has not been well studied. Therefore, we focused on studying the biological functions of IMP3 in SCC and KA. In human skin SCC cell lines, HSC-1 and HSC-5, and the human keratinocyte cell line, HaCaT, IMP3 mRNA levels were significantly higher than that of normal human skin. The knockdown of IMP3 expression reduced the proliferation of HSC-1, and significantly reduced invasion by HSC-1 and HSC-5. In contrast, the knockdown of IMP3 did not significantly affect invasion by HaCaT cells. In immunohistochemical studies of SCC and KA tissues, the Ki-67 labeling index (LI) of the suprabasal cell layer was significantly higher in SCC, compared with KA tissues and the tumor-free margin (TFM) adjacent to SCC and KA. Most SCC tissues stained strongly positive for IMP3, but KA tissues and TFM were mostly negative for IMP3. The Ki-67 LI of the IMP3-positive group was significantly higher than that of the IMP3-negative group in the suprabasal cell layer of SCC. These results suggest that IMP3 plays an important role in proliferation and, more significantly, in the invasion of SCC, and may be a suitable marker for the histopathological diagnosis of SCC with a crateriform architecture and KA. Furthermore, IMP3 may potentially be a new therapeutic target for SCC. |
| 8. | Ohashi, Ryuji; Hayama, Ayako; Matsubara, Miyuki; Watarai, Yasuhiko; Sakatani, Takashi; Takei, Hiroyuki; Naito, Zenya Fine needle aspiration cytology of signet ring cells in breast carcinoma: A cytohistological study of 11 cases Journal Article In: International Journal of Clinical and Experimental Pathology, vol. 9, no. 6, pp. 6414–6422, 2016, ISSN: 19362625. @article{Ohashi2016b,Signet ring cell (SRC) carcinoma is a unique subtype of adenocarcinoma; however, the clinicopathological profiles of SRCs in breast carcinoma are yet to be determined. Here, we investigated cyto-histological findings of 11 breast carcinoma cases with SRCs comprising more than 20% of the tumor cells; invasive ductal carcinoma (IDC) (n=4), invasive lobular carcinoma (ILC) (n=4), pleomorphic lobular carcinoma (PLC) (n=1), and mucinous carcinoma (MC) (n=2). The mean age of the patients was 60.2 ± 13 years, and the mean tumor size was 2.0 ± 0.8 cm. Three cases of IDC, 1 PLC, and 1 of MC had grade 2 or 3 nuclear atypia, whereas 1 case of IDC, 4 of ILC, and 1 of MC had grade 1 nuclear atypia. Axillary lymph nodes were positive for metastatic carcinoma in 1 patient with IDC and 1 with ILC. In fine needle aspiration smears, intracytoplasmic lumen (ICL) type SRCs were found to be major constituents of SRCs in ILC and PLC, while non-ICL type SRCs were predominant in IDC. MC tumors had SRCs of both ICL and non-ICL types. During our follow-up period ranging from 97 to 3650 (mean 1458 ± 1055) days, all the patients were alive without recurrence of the tumor. Our results indicate that the nature of SRCs may vary with the histological subtype of breast cancer, but its presence may not indicate poor prognosis. A large study with more cases of breast cancer with SRCs for a longer period may be needed to determine the clinical significance of SRCs. |
| 1. | Kure, Shoko; Wada, Ryuichi; Peng, Wei Xia; Ishii, Hideaki; Kitamura, Taeko; Fujii, Takenori; Inai, Shunta; Nagao, Toshitaka; Naito, Zenya A case of oncocytic papillary cystadenocarcinoma of the parotid gland—Pathological and molecular features of a rare tumor Journal Article In: Human Pathology: Case Reports, vol. 5, pp. 18–22, 2016, ISSN: 22143300. @article{Kure2016,We present histological, immunohistochemical and molecular features of oncocytic papillary cystadenocarcinoma, a rare neoplasm of the salivary and parotid glands, in an 82-year-old Japanese man. The resected tumor was solid nodular mass with fibrous capsule. The tumor was composed of papillary proliferation of tall columnar cells with thin vascular cores. The cytoplasm of the tumor cells was granular and eosinophilic. The tumor cells showed clear positive reaction for mitochondria and androgen receptor. GCDFP15 and HER2 were negative. Electron microscopy demonstrated numerous mitochondria in the cytoplasm of the tumor cells. Ki-67 index was 30%. Most of the tumor cells were positive for TP53, and single nucleotide polymorphism was found at codon 151. The invasion into the lymphatic spaces and capsule was noted. Although recurrence and metastasis were not noted at one and a half years after the resection, the patient needs to be followed up under careful observation. |
| 2. | Tomori, Yuji; Ohashi, Ryuji; Naito, Zenya; Nanno, Mitsuhiko; Takai, Shinro Florid reactive periostitis in the fifth phalange of a professional boxer: A case report Journal Article In: Medicine (United States), vol. 95, no. 51, pp. e5697, 2016, ISSN: 15365964. @article{Tomori2016,Rationale: Florid reactive periostitis is a rare, benign bone and chondrogenic lesion that develops most frequently in the phalanges of the hands. Although the definitive cause of florid reactive periostitis is unknown, the major inciting factor is generally considered to be trauma, including repetitive minor trauma. Patient concerns: We present a case of florid reactive periostitis affecting two contiguous phalangeal bones of the left fifth phalange of a 23-year-old male professional boxer. The patient had experienced chronic pain around the metacarpophalangeal joint of the left fifth phalange when punching with the left hand; this pain was improved but not resolved after conservative treatment. Interventions: Plain radiography of the fifth phalange revealed a bulging bone lesion on the volar side of the proximal phalanx and metacarpal of the left fifth phalange. Computed tomography also showed raised bony lesions on the volar side of these bones without bony destruction or intraregional calcification. Surgery was performed and histopathology revealed that the bone specimens comprised a mixture of fibrous connective tissue and relatively immature bone covered by bland osteoblasts. Diagnoses: These findings were suggestive of a benign bone formation process, and the lesion was diagnosed as florid reactive periostitis. Outcomes: The pain and tenderness in the left fifth phalange experienced during boxing had completely resolved by 6 months postoperatively, and 12 years postoperatively the patient had full range of motion and no recurrence of pain. Lessons: Traction force, such as those associated with "leading jabs," may induce repetitive minor trauma and subsequent periosteal damage, resulting in the gradual development of bulging bone ridges on the volar surface of the proximal fifth phalange and metacarpus of the hand. Abbreviations: FRP = florid reactive periostitis |
| 1. | Ohashi, Ryuji; Matsubara, Miyuki; Watarai, Yasuhiko; Yanagihara, Keiko; Yamashita, Koji; ichi Tsuchiya, Shin; Takei, Hiroyuki; Naito, Zenya Cytological features of complex type fibroadenoma in comparison with non-complex type fibroadenoma Journal Article In: Breast Cancer, vol. 23, no. 5, pp. 724–731, 2016, ISSN: 18804233. @article{Ohashi2016a,Background: To determine the cytomorphological features of complex type fibroadenoma (CFA), we reviewed fine needle aspiration (FNA) cytology with correlation to its histopathology findings, and compared them with non-complex type fibroadenoma (NCFA). Methods: From excisional biopsy or resected specimens of fibroadenoma (FA) cases treated at our institution from 2004 to 2013, we chose 46 patients who underwent FNA before a diagnosis of FA was established. We histologically re-classified them into two groups: CFA and NCFA. FNA diagnosis was retrospectively re-evaluated from FNA reports. We further re-assessed detailed characteristics of each FNA smears to identify cytomorphological features of CFA. Results: We found that 15 cases fulfilled the diagnostic criteria of CFA, in which 7 (46.7 %) had an FNA diagnosis of “suspicious for malignancy” or “indeterminate” while only 2 NCFA cases had that of “indeterminate” (p = 0.004). FNA smears from CFA cases showed discohesiveness, enlarged nuclei, prominent nucleoli, and fewer myoepithelial cells more often than NCFA. Although no significant difference was noted in patients' age and tumor size between CFA and NCFA, 5 CFA cases (33.3 %) were accompanied by the presence of carcinoma in the same breast or the contralateral breast while no NCFA cases had carcinoma in the breast. Conclusions: FNA of CFA can lead to erroneous or indeterminate interpretation, due to proliferative and/or hyperplastic changes of ductal epithelium with or without atypia. It is important to recognize the disease entity and characteristic cytomorphological findings of CFA to reach accurate FNA diagnosis of breast lesions. |
| 2. | Wada, Ryuichi; Arai, Hiroki; Kure, Shoko; Peng, Wei Xia; Naito, Zenya “Wild type” GIST: Clinicopathological features and clinical practice Miscellaneous 2016, ISSN: 14401827. @misc{Wada2016,Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Mutation of KIT and PDGFRA genes is implicated in the tumorigenesis. Approximately 10% of GISTs do not harbor mutation of these genes, and they are designated as “wild type” GIST. They are classified into succinate dehydrogenase (SDH)-deficient and non-SDH-deficient groups. SDH-deficient group includes Carney triad and Carney Stratakis syndrome. The patients are young women. Tumors occur in the antrum of the stomach, and tumor cells are epithelioid. Lymph node metastasis is frequent. The non-SDH-deficient group includes neurofibromatosis (NF) type 1 and GISTs with mutations of BRAF, KRAS, and PIK3CA and with the ETV6-NTRK3 fusion gene. GIST in NF occurs in the small intestine, and tumor cells are spindle shaped. GIST with BRAF mutation arises in the small intestine. Attention to the age, gender, family history and other neoplasms may raise the prediction of syndromic disease. Location of the tumor, morphology, and pleomorphism of the tumor cells are further informative. Lymphovascular invasion should be carefully evaluated. The determination of KIT expression is essential for the diagnosis. When wild type GIST is suspected, intensive genetic analysis is required. Further, a careful and long-time observation is recommended. |
| 3. | Tsuchiya, Shin-ichi; Yamaguchi, Rin; Tsuchiya, Kyoko; Ohashi, Ryuji Characteristics of the Japanese histological classification for breast cancer: correlations with imaging and cytology Journal Article In: Breast Cancer, vol. 23, no. 4, pp. 534–539, 2016, ISSN: 1340-6868. @article{Tsuchiya2016,The Japanese histological classification of breast cancer is a unique classification that was published as the 2nd edition of the General Rules for Clinical and Pathological Recording of Breast Cancer in 1971. According to this classification, breast cancers are divided into three subgroups: noninvasive, invasive, and Paget's disease. Invasive carcinomas are further divided into two groups: invasive ductal carcinomas (IDCs) and special types. IDCs are the most common types, representing 70–80 % of all breast cancers, and most of them correspond to invasive carcinoma—not special type—according to the latest WHO classification (4th edition). In particular, IDCs are subdivided into three subgroups as follows: (1) papillotubular carcinoma, which is characterized by the projection of papillae into spaces, and includes cribriform and comedo patterns; (2) solid-tubular carcinoma, which is a solid cluster of cancer cells with expansive growths that form relatively sharp borders; and (3) scirrhous carcinoma, which grows in a scirrhous manner characterized by cancer nests or cells accompanied by marked fibrosis. The concept of subclassification originated in Japan. The Japanese histological classification has taken on important roles since its publication, in particular for comparisons between histology and imaging or cytology. |