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Testicular teratomas are the major histologic type of testicular germ cell tumors and their incidence continues to grow. Moreover, teratomas can develop from undifferentiated cells in induced pluripotent stem (iPS) cell transplantation therapy, seriously hampering the progress of regenerative medicine. Germinal center-associated nuclear protein (GANP) is thought to be important to the biogenetic control of primordial germ cells and is among the genes susceptible to testicular germ cell tumors. Thus, we analyzed the expression of GANP in human testicular postpubertal-type teratomas and established a novel mouse model to reveal the association between GANP and teratomagenesis. We analyzed 31 cases of human testicular postpubertal-type teratomas and, in all cases, GANP was overexpressed. The aberrant expression was also detected in germ cell neoplasia in situ accompanied by the teratoma. GANP expression was particularly high in the epithelia of the epidermis, cutaneous appendages, and trachea-like ciliated epithelium. To further clarify the association between GANP and teratomagenesis, we established a novel teratomagenesis mouse model (CAG-ganp

Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P

Epignathus is an extremely rare teratoma found in the oral cavity or oropharyngeal region of newborns, whose pathogenesis is poorly understood. We describe a giant epignathus arising from the oropharynx in a newborn. The giant tumor completely obstructed the airway of the newborn resulting in death. Histological and radiological examination of the tumor reveals the presence of a remarkably well-developed skeleton of the head and neck. A row of teeth, the axis and atlas, thyroid and salivary glands, trachea, and cerebral tissue are all detected within the tumor. These findings suggest that the epignathus is fetus-in-fetu which is considered a type 0 germ cell tumor in accordance with current literature.

Serous cystic neoplasm (SCN) is a potentially malignant and invasive disease. However, there are no established guidelines regarding the surgical management of SCN. Here, we report a case of SCN with jejunal invasion that ultimately required a distal pancreatectomy with partial resection of the jejunum. The patient was a 65-year-old female who was referred to our department after a diagnosis of SCN in the pancreatic tail. CT and MRI showed a 75-mm multifocal cystic mass with calcifications; the splenic vein and left adrenal vein were entrapped within the tumor. Furthermore, the tumor was in contact with the beginning of the jejunum. Finally, she underwent a posterior radical antegrade modular pancreatosplenectomy with a partial wedge-shaped resection of the jejunum. Histological findings indicated serous cystadenoma. In addition, the tumor cells were found to have infiltrated the jejunal muscularis propria in some areas, suggesting that the tumor had malignant potential. Currently, 14 months have passed since surgery and there is no evidence of metastasis or recurrence. Surveillance and the decision to perform surgical resection should be made based on tumor size and growth rate to avoid malignant transformation as well as to provide SCN patients with organ-sparing, less invasive surgery.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014.In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded.This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.

Background Evolutionary cancer has a supply mechanism to satisfy higher energy demands even in poor-nutrient conditions. Metabolic reprogramming is essential to supply sufficient energy. The relationship between metabolic reprogramming and the clinical course of pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to clarify the differences in metabolic status among PDAC patients. Methods We collected clinical data from 128 cases of resectable PDAC patients undergoing surgery. Sixty-three resected tissues, 15 tissues from the low carbohydrate antigen 19-9 (CA19-9), 38–100 U/mL, and high CA19-9, > 500 U/mL groups, and 33 non-tumor control parts, were subjected to tandem mass spectrometry workflow to systematically explore metabolic status. Clinical and proteomic data were compared on the most used PDAC biomarker, preoperative CA19-9 value. Results Higher CA19-9 levels were clearly associated with higher early recurrence (p p p = 0.025). From proteomic analysis, we discovered that cancer evolution-related as well as various metabolism-related pathways were more notable in the high group. Using resected tissue immunohistochemical staining, we learned that high CA19-9 PDAC demonstrated aerobic glycolysis enhancement, yet no decrease in protein synthesis. We found a heterogeneity of various metabolic processes, including carbohydrates, proteins, amino acids, lipids, and nucleic acids, between the low and the high groups, suggesting differences in metabolic adaptive capacity. Conclusions Our study found metabolic adaptation differences among PDAC cases, pertaining to both cancer evolution and the prognosis. CA19-9 can help estimate the metabolic adaptive capacity of energy supply for PDAC evolution.

Background/Aims: Behçet’s disease (BD) with intestinal lesions and Crohn’s disease (CD) share clinical features. However, no report has compared the 2 diseases with regard to lesions of the upper gastrointestinal tract (UGT). We aimed to evaluate endoscopic and histologic findings of UGT in CD and BD. Methods: We retrospectively assessed the endoscopic records and biopsy samples of 84 Helicobacter pylori-negative patients (50 CD, 34 BD). In duodenal samples, MUC5AC immunohistochemical analysis was performed to identify gastric foveolar metaplasia. Results: In endoscopic findings, bamboo joint-like appearance (17/50 CD, 0/34 BD) and erosions (14/50 CD, 2/34 BD) were significantly more frequent in CD gastric lesions (p < 0.001, and p = 0.012). In histologic findings of stomach, focal neutrophil infiltration in lamina propria (15/48 CD, 1/34 BD) was significantly more frequent in CD (p < 0.001). In that of duodenum, wide gastric foveolar metaplasia (19/49 CD, 1/34 BD) was significantly more frequent in CD duodenal lesions (p = 0.013). The mean maximum width of the gastric foveolar metaplasia was 114.0 ± 10.6 and 29.5 ± 4.5 μm for CD and BD respectively (p = 0.003). Conclusions: In H. pylori-negative patients, gastric focal neutrophil infiltration and wide duodenal gastric foveolar metaplasia were important for distinguishing CD from BD.

Background Intra-ampullary papillary-tubular neoplasm (IAPN) has been classified as a Vater papillary tumor. The prognosis of IAPN is generally relatively good. Here, we describe a patient with a mucinous adenocarcinoma cluster in the Vater papilla of IAPN origin. Clinical presentation The patient was a 66-year-old man who was admitted to our hospital after a diagnosis of pancreatic head carcinoma based on a pancreatic duct dilatation found on abdominal ultrasound. CT showed a 40 mm lesion in the pancreatic head and expansion of the main pancreatic duct to a maximum diameter of 9 mm on the caudal side of the lesion. The extrahepatic bile duct had also expanded to a maximum diameter of 8 mm. PET/CT showed fluorodeoxyglucose (FDG) accumulation of SUVmax 6.02 that corresponded to the tumor in the pancreatic head, though it did not suggest distant metastasis. The patient was diagnosed with pancreatic head carcinoma T3 N0 M0 Stage IIA and underwent a pancreaticoduodenectomy. Pathology indicated that the tumor in the pancreatic head was a benign inflammatory lesion. On the other hand, the papillotubular tumor pervading the lumen in the duodenal papillary common channel met the criteria for IAPN, and a mucinous adenocarcinoma cluster found in the surrounding stroma suggested malignant transformation of IAPN. No metastasis to lymph nodes was demonstrated. With regard to the mucus phenotype of each lesion, the IAPN was MUC2 and MUC5AC positive, while the mucinous adenocarcinoma was MUC2-positive and MUC5AC-negative. In addition, CD10 was negative in both lesions, suggesting that mucus transformation from the gastric type to the intestinal type was a key element. A blood test 10 months after surgery showed increased CA19-9 (105 U/mL) and CEA (7.1 ng/mL). Abdominal CT showed multiple cystoid nodes in the liver, which were diagnosed as multiple liver metastases of mucinous adenocarcinoma transformed from the IAPN. Conclusions We reported a case with IAPN that developed in the Vater papilla, which took an extremely malignant course. IAPN generally has a good prognosis, but it is important to understand that a malignant course may occur.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an infiltrative growth pattern with intense desmoplastic stroma comprised of cancer-associated fibroblasts (CAFs). Additionally, the histological characteristics are considered to play a vital role in the poor prognosis of PDAC. However, the density of cancer cells, degree of desmoplasia and vascular proliferation varies in individual cases. We hypothesized that preoperative radiological images would reflect histological characteristics, such as cancer cell density, CAF density and microvessel density. To clarify the association between the histological characteristics and radiological images of PDAC, the cancer cell density, CAF density and microvessel density from surgical specimens were measured with immunostaining, and the time density curve of dynamic contrast-enhanced computed tomography (CECT) was analyzed. Overall, the initial slope between non-enhanced and arterial phases was correlated with microvessel density, and the second slope between arterial and portal phases was correlated with CAF and cancer cell densities. In conclusion, the present study suggested the possibility of estimating cancer cell, CAF and microvessel densities using the TDC of dynamic CECT.

STEROIDOGENESIS IN HEPATIC MUCINOUS CYSTIC NEOPLASM Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.

Sporadic amyotrophic lateral sclerosis (sALS) is characterized pathologically by loss of upper and lower motor neurons with occurrence of transactivation response DNA-binding protein 43 kDa (TDP-43)-immunoreactive skein-like and round hyaline inclusions. Lewy body-like hyaline inclusions (LBHIs) are also found in a small proportion of sALS cases as well as in individuals with familial ALS with mutations in the Cu/Zu superoxide dismutase (SOD1) gene. LBHIs in sALS are immunopositive for TDP-43, but not for SOD1. The occurrence of Bunina bodies (BBs) is another key pathological feature of sALS. BBs are immunonegative for TDP-43 but immunopositive for cystatin C, transferrin, peripherin and sortilin-related receptor CNS expressed 2 (SorCS2). Despite differences between BBs and TDP-43 inclusions in terms of protein constituents and ultrastructure, the two inclusions are known to be linked. We recently encountered a case of sALS of 10 months duration in which many round hyaline inclusions, LBHIs and BBs were found in the anterior horn cells of the spinal cord. Our immunohistochemical and ultrastructural examinations revealed the presence of BBs within the skein-like and round hyaline inclusions, and in the LBHIs. Colocalization of BB-related proteins (cystatin C, transferrin and SorCS2) and TDP-43 was also confirmed in the halo of LBHIs as well as in the marginal portion of the skein-like and round hyaline inclusions. These findings suggest that there is some relationship between BBs and TDP-43-immunoreactive inclusions in terms of their formation processes.

Background: Given the importance of neutrophil recruitment in the pathogenesis of glomerulonephritis (GN), the representative neutrophil chemoattractant C-X-C motif chemokine 1 (CXCL1)/GROα and the adhesion molecule E-selectin in glomerular endothelial cells (GECs) play a pivotal role in the development of GN. Endothelial Toll-like receptor 3 (TLR3) is thought to be involved in the inflammatory response via innate immunity. However, the role of endothelial TLR3 signaling in the expression of neutrophil chemoattractants and adhesion molecules remains to be elucidated. Thus, we aimed to examine this issue. Methods: We treated normal human GECs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expressions of CXCL1 and E-selectin using quantitative real-time reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. To further elucidate the poly IC-induced signaling pathway, we subjected the cells to RNA interference against TLR3, interferon (IFN)-β, nuclear factor (NF)-κB p65, and IFN regulatory factor (IRF) 3. We also used immunofluorescence to examine the endothelial expression of CXCL1 in biopsy specimens from patients with crescentic and non-crescentic purpura nephritis (PN). Results: We found that the activation of TLR3 induced the endothelial expression of CXCL1 and E-selectin, and that this involved TLR3, ­NF-κB, IRF3, and IFN-β. Intense endothelial CXCL1 expression was observed in biopsy specimens from patients with crescentic PN. Conclusion: These findings support a role for glomerular antiviral innate immunity in the pathogenesis of GN. Intervention of glomerular TLR3 signaling may therefore be a suitable therapeutic strategy for treating GN in the future.

// Shogo Hosogoe 1 , Shingo Hatakeyama 1 , Ayumu Kusaka 1 , Itsuto Hamano 1 , Yoshimi Tanaka 1 , Kazuhisa Hagiwara 1 , Hideaki Hirai 2 , Satoko Morohashi 2 , Hiroshi Kijima 2 , Hayato Yamamoto 1 , Yuki Tobisawa 1 , Tohru Yoneyama 3 , Takahiro Yoneyama 1 , Yasuhiro Hashimoto 3 , Takuya Koie 1 and Chikara Ohyama 1, 3 1 Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan 2 Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan 3 Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan Correspondence to: Shingo Hatakeyama, email: shingoh@hirosaki-u.ac.jp Keywords: renal cell carcinoma, presurgical therapy, axitinib, radiological response Received: March 29, 2017 Accepted: May 04, 2017 Published: May 17, 2017 ABSTRACT Background and Objective: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. Results: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib ( n = 26), everolimus ( n = 3), sunitinib ( n = 1), and axitinib followed by temsirolimus ( n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were −19%, −24%, and −49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. Materials and Methods: Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. Conclusions: CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

Pathological stage is the most important prognostic factor in patients with lung cancer, and is defined according to the tumor node metastasis classification system. The present study aimed to investigate the clinicopathological significance of lymphatic invasion in 103 patients who underwent surgical resection of lung squamous cell carcinoma (SqCC). The patients were divided into two groups, according to the degree of lymphatic invasion: Those with no or mild lymphatic invasion (ly0-1) and those with moderate or severe lymphatic invasion (ly2-3). Ly2-3 was associated with tumor size (P=0.028), lymph node metastasis (P

The functions of differentiated embryonic chondrocyte gene (DEC) 1, a basic helix-loop-helix (bHLH) transcription factor, have been reported to be associated with the regulation of mammalian circadian rhythms, differentiation of chondrocytes and skeletal muscles, apoptosis, hypoxia-induced reactions and epithelial mesenchymal transition. Our previous report showed that another bHLH transcription factor DEC2 constitutes a negative feedback loop in Toll-like receptor 3 (TLR3)/interferon (IFN)-β-mediated inflammatory responses in human mesangial cells. However, the role of DEC1 in innate immune responses remains unclear. We have previously reported TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and TLR3/IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in cultured normal human mesangial cells treated with polyinosinic-polycytidylic acid (poly IC), a synthetic double-stranded RNA that is sensed by TLR3. The present study was carried out to examine the involvement of DEC1 in these axes. DEC1 was constitutively expressed in human mesangial cells, and the expression was not altered by treatment with poly IC. Interestingly, RNA interference against DEC1 markedly enhanced the poly IC-induced expression of chemokines CXCL10 and CCL5. Knockdown of DEC1 increased the poly IC-induced MDA5 and RIG-I protein expression without affecting mRNA expression, and did not affect phosphorylation of signal transducer and transcription 1 (STAT1). DEC1 may serve as an anti-inflammatory factor by negative regulation of MDA5/CXCL10 and RIG-I/CCL5 in human mesangial cells treated with poly IC.

Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix-loop-helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis-related markers in human esophageal squamous cell carcinoma TE-11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively. Following cisplatin treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited expression of the pro-apoptotic factor Bim and slightly increased the anti-apoptotic factor Bcl-xL. However, overexpression of DEC1 during cisplatin treatment failed to affect expression of these markers. Additionally, overexpression of DEC2 improved cell viability and decreased cell apoptosis induced by cisplatin. These results suggested that DEC2 exhibits anti-apoptotic effects in TE-11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may therefore have therapeutic potential for the treatment of esophageal cancer, in combination with cisplatin.

Overlap syndrome between primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) is extremely rare in Japan. We herein report two adult patients with PSC-AIH overlap syndrome. They were diagnosed with PSC-AIH overlap syndrome based on the findings of endoscopic retrograde cholangiography and liver biopsy, and using the International Autoimmune Hepatitis Group scoring system. In both cases, PSC preceded AIH, and combination therapy with steroid and ursodeoxycholic acid was effective. Because there are few reported cases in Japan, it is important to study more cases to shed light on the clinical and pathological features of PSC-AIH overlap syndrome.

Background: Among historical nature remedies in Eastern Asia, Huaier (Trametes robiniophila murr) has long been reported for its significant efficacy on longevity and health maintenance, and more importantly, on cancer. The target cancers of Huaier show the almost complete overlap with those strongly influenced by the Hippo pathway function, which is also well known as a tumor suppressor mechanism. Objective: We have initiated the present study in order to prove the hypothesis that the Hippo signaling pathway is a main molecular mechanism of Huaier effects on cancer and on multiple physiological disorders. Methods: We performed in vivo study using Drosophila flies genetically disrupted transcriptional control in the Hippo pathway with overexpressing non-phosphorylatable Yorkie (Yki:V5S168A) as a cancer model. In addition, metabolome analysis was performed using those cancer-model mutants with a comparison to healthy controls. Results: The administration of Huaier clearly resulted in the recovery of rough eye formation of the mutants, indicating the rescue of tumor suppressor mechanism disrupted by the genetically inoculated overabundant transcriptional activators. These improvements occurred in a dose-dependent manner, just as shown in clinical observations. Simultaneously, the GC/MS-based metabolome analysis revealed that Huaier uptake lead the metabolic profile of the mutant flies strongly shifted to that of the early developmental stage. Conclusion: The present study emphasizes that a broad spectrum of Huaier effects was based on the rescue of the disrupted Hippo signaling pathway control, especially on the recovery in transcriptional dysregulation. The metabolome profile shift would explain the molecular basis of the tissue recovery after a long course of Huaier treatment, by the potential to modulate the cell fate through the embryogenesis and subsequent normal specification of the cells in the damaged tissues.

Biliary atresia (BA) is a disease of the newborn that is characterized by progressive, inflammatory and sclerosing cholangiopathy. Innate immune responses to viral components are thought to be involved in the pathogenesis of BA. It is also reported that some chemokines, such as CCL5, are possibly involved in the pathogenesis of experimental animal model of BA. We treated human biliary epithelial HuCCT1 cells with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA (dsRNA) which mimics viral RNA, and analyzed the CCL5 expression by quantitative reverse transcription-PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). To examine the regulation mechanisms of CCL5, we subjected the cells to RNA interference (siRNA) against Toll-like receptor 3 (TLR3), interferon (IFN)-β, NF-κB p65 and IFN regulatory factor (IRF) 3. Immunohistochemical staining for CCL5 was also performed in tissues from patients with BA. Poly IC induced CCL5 expression in HuCCT1 cells. CCL5 expression induced by poly IC was inhibited by the knockdown of TLR3, p65 or IRF3, but it was not affected by knockdown of IFN-β. Immunohistochemical staining showed that CCL5 was strongly expressed in biliary epithelial cells of patients with BA. The current study suggests that TLR3 signaling induces CCL5 expression via NF-κB and IRF3 in bile duct cells, and this pathway may be involved in the pathogenesis of BA.

Differentiated embryonic chondrocyte (DEC) 1 has been reported to be involved in cell differentiation, hypoxia response, and cancer progression. Recent studies have demonstrated that hypoxia-inducible factor (HIF)-1α induces epithelial-mesenchymal transition (EMT) in carcinoma cells to facilitate cell invasiveness and metastasis. However, it remains unclear whether DEC1 participates in hypoxia-mediated EMT processes. In the present study, we reported that hypoxia induced DEC1 expression in hepatocellular carcinoma (HCC) HepG2 cells, and DEC1 negatively regulated expression of HIF-1α and E-cadherin in transcriptional/translational levels. Cell morphological changes were evaluated with hematoxylin and eosin (H-E) staining. Exposure to hypoxia caused spindle-like shape in some of the HepG2 cells, and DEC1 overexpression furthered these changes. In conclusions, DEC1 is involved in hypoxia-induced EMT processes via negatively regulating E-cadherin expression in HepG2 cells.

A 69-year-old woman had received hemodialysis for chronic renal failure and was taking lanthanum carbonate since 63 years of age. She presented with appetite loss and nausea. We performed esophagogastroduodenoscopy, which revealed multiple longitudinal white plaques in the esophagus. Lesion biopsies showed lanthanum deposition, and lanthanum carbonate was found histologically by energy-dispersive X-ray spectroscopy. The plaques of this patient appeared like those of dabigatran-induced esophagitis, and may have occurred due to long-term contact of the esophageal epithelium with lanthanum carbonate because patient spent time in lying state. Although a few studies regarding lanthanum deposition in the stomach have been conducted, there are no reports on lanthanum deposition in the esophagus. This case suggests that the presence of longitudinal white plaques in the esophagus may indicate lanthanum deposition.

Background The malignant transformation of an ectopic pancreas in the duodenum is extremely rare. Herein, we report a case of an adenocarcinoma that arose from an ectopic pancreas. We also reviewed 14 cases of malignant transformations arising from an ectopic pancreas in the duodenum that were previously published. Case presentation An 81-year-old man with a 1-month history of vomiting was admitted to our institution. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) scans revealed an obstruction at the first part of the duodenum. A distal gastrectomy was performed for diagnostic and therapeutic purposes. The histopathological examination of the resected specimen showed adenocarcinoma that arose from an ectopic pancreas (Heinrich type 1). The patient is alive without relapse at 18 months of follow-up. Conclusions Adenocarcinoma that arises from an ectopic pancreas should be considered when an obstruction is identified in the duodenum.

In patients with rectal cancer treated with neoadjuvant chemotherapy (NAC), differences are often observed between high and low radiological image reduction effects. It may be suggested that high radiological image reduction indicates a beneficial response to chemotherapy. However, the pathological investigation of the differences between high and low radiological cancer volume reduction cases remains limited. In the current study, a total of 50 patients with rectal cancer, treated with NAC, were examined. The approximate pathological primary cancer area and the radiological cancer volume reduction ratio were measured using CT and/or MRI imaging and the donut-shaped measurement method. Immunostaining of cytokeratin AE1/AE3 was performed to quantitatively measure the cancer cell mass in the largest section of rectal cancer. Cytokeratin AE1/AE3-stained area (P=0.04), mitosis (P=0.0027) and radiological donut-shaped images after NAC (P=0.010) were lower in the high radiological cancer volume reduction ratio group compared with the low radiological cancer volume reduction ratio group. These findings indicate that the radiological images had some ability to determine the treatment effect and clinicopathological characteristics of patients with rectal cancer treated with NAC.

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosomal proteins BP180 and BP230/BPAG1e. Whereas the role of anti-BP180 antibodies has been extensively characterized, the pathogenicity of anti-BPAG1e antibodies remains unclear. The purpose of this study is to elucidate the role of antibodies to BPAG1e in the experimental bullous pemphigoid models. We generated Bpag1 conditional knockout mice, where the knockout of Bpag1 is restricted to keratin 5–expressing epithelial cells. Bpag1 conditional knockout mice were immunized with the C-terminal portion of BPAG1e, and the splenocytes were injected into Rag2−/− mice intravenously. The recipient mice presented with erosion on the feet and tails. Microscopic examination showed subepidermal blisters and a linear deposition of IgG at the dermal-epidermal junction. To assess the potential role of trauma on BP development, we inflicted surface wounds on the dorsum of the Rag2−/− recipient mice after adoptive transfer. The wounded Rag2−/− mice had increased morbidity and severity of BP-like symptoms. Moreover, the depletion of B cells from splenocytes abolished a subepidermal blistering phenotype in vivo. These findings demonstrate that antibodies to BPAG1e might play a pathogenic role in causing subepidermal blistering, and external factors, including trauma, might be a trigger for BP development.

Objectives Mucin phenotype is a tool to classify gastric cancer, but the relationship between mucin phenotype and its malignancy is still controversial. This study aimed to clarify the relationship between mucin phenotype and the malignant potential of gastric cancer. Methods A total of 82 cases of early-stage differentiated adenocarcinoma (submucosal invasion cases) obtained from surgeries were studied by immunohistochemistry. Gastric mucin phenotype and E-cadherin expression were analyzed in the mucosal and submucosal layer. E-cadherin expression was analyzed by using imaging software (ImageJ) for objective data analysis. Furthermore, the mucin phenotypic shift was analyzed from mucosa to submucosa. Results We found that: (1) tumors with intestinal mucin phenotype had statistically more venous invasion in the submucosal lesion; (2) tumors with an intestinal phenotype that showed venous invasion in the submucosal lesion had a higher percentage of tumors that showed loss of phenotype; (3) no dominant change in E-cadherin expression was observed from the mucosa to submucosa. Conclusion Tumors with loss of phenotype and submucosal intestinal phenotype showed predominantly more venous invasion, so examining the identification of phenotypes and phenotype shifts can be expected to be a factor that influences treatment strategies after endoscopic treatment or after surgical resection.

The functions of basic helix-loop-helix (bHLH) transcription factor-differentiated embryonic chondrocyte (DEC)1 (BHLHE40) and 2 (BHLHE41) are involved in various fields such as circadian rhythms, immune responses, cell proliferation, hypoxia reaction as well as malignant tumors. Previous findings showed that DEC served as apoptosis regulators of various cancer cell lines. However, little is known regarding the expression of DEC1 and DEC2 in prostate cancer cells. The present study aimed to examine the roles of DEC1 and DEC2 in human prostate cancer DU145 and PC-3 cells that were treated with paclitaxel. The expression of DEC1 and DEC2 was decreased in DU145 cells but was increased in PC-3 cells when treated with paclitaxel. DU145 cells were more sensitive to paclitaxel than PC-3 cells since the amount of cleaved poly(ADP-ribose) polymerase (PARP) reached its peak at 50 µM of paclitaxel in DU145 cells but at 100 µM in PC-3 cells. In addition, the amount of cleaved PARP was decreased by DEC1 siRNA, while it was increased by DEC2 siRNA in the presence of paclitaxel. Although DEC2 overexpression slightly inhibited cleaved PARP in the two cell lines, the effects of DEC1 overexpression on apoptosis remain to be determined. In conclusion, DEC1, at least partly, exerted a pro-apoptotic effect, whereas DEC2 exerted an anti-apoptotic effect in paclitaxel-induced apoptosis of human prostate cancer cells.

Both the invasive growth types of colorectal cancer (CRC) and the number of myofibroblasts have been associated with histopathological factors such as lymph node and liver metastasis, and local recurrence. However, there are few studies, that have assessed the association between invasive growth type and myofibroblast distribution in CRC. We aimed to evaluate the relationship between the clinicopathological factors of CRC and two invasive growth types, the expanding and infiltrating types. We categorized 150 cases of pT3 CRC into the expanding and infiltrating types and measured the myofibroblast density of three histological layers: the submucosa (SM), the muscularis propria (MP) and the subserosa (SS). We compared these two invasive growth types and analyzed the relationship between clinicopathological factors and myofibroblast density. Myofibroblast density was significantly higher in the infiltrating type than that in the expanding type (P