Kenji Fujiwara

Pancreatic stellate cells (PSCs) play a crucial role in the aggressive behavior of pancreatic cancer. Although heterogeneity of PSCs has been identified, the functional differences remain unclear. We characterized CD271(+) PSCs in human pancreatic cancer. Immunohistochemistry for CD271 was performed for 31 normal pancreatic tissues and 105 pancreat...

CD105 expression correlates with prognosis for several cancers. However, its significance in pancreatic cancer is unclear. We analyzed CD105 expression in resected pancreatic cancer tissue and pancreatic cancer cell lines, compared the properties of CD105 and CD105 cells using quantitative RT-PCR and migration assays, and evaluated the relationship...

CD166, also known as activated leukocyte cell adhesion molecule (ALCAM), is expressed by various cells in several tissues including cancer. However, the role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer.We performed immu...

Background Unexpected gallbladder cancer (UGBC) is sometimes found in the resected gallbladder of patients during or after surgery. Some reports have indicated UGBC identification rates for all gallbladder surgeries, but scarce data are available for the UGBC identification rates for specific gallbladder diseases. The present study was performed to...

295 patients with GSWs were treated at Juba Military Hospital, South Sudan. • Patient demographics, injury characteristics, and clinical outcomes were collected and the relationships between various factors and wound infection were analyzed. • We used Chi-square test, Fisher's exact probability test, and logistic regression analysis.

Data of admitted 138 patients comprising 77 orthopedic cases, 16 general surgical cases, and 4 plastic surgery cases were collected and analyzed; wound types, treatment methods, and patient outcomes were collected, including infection rates and the need for reconstructive surgery.

Axon guidance molecules are frequently altered in pancreatic ductal adenocarcinoma (PDA) and influence PDA progression. However, the molecular mechanism remained unclear. Using genetically engineered mouse models to examine semaphorin 3D (SEMA3D), we identified a dual role for tumor- and nerve-derived SEMA3D in the malignant transformation of pancr...

Evaluation of the cystic duct anatomy prior to bile duct or gallbladder surgery is important, to decrease the risk of bile duct injury. This study aimed to clarify the frequency of cystic duct variations and the relationship between them. Data of 205 patients who underwent cholecystectomy after imaging at Sada Hospital, Japan, were analyzed. The Ch...

Axon guidance molecules were found to be the gene family most frequently altered in pancreatic ductal adenocarcinoma (PDA) through mutations and copy number changes. However, the exact molecular mechanism regarding PDA development remained unclear. Using genetically engineered mouse models to examine one of the axon guidance molecules, semaphorin 3...

Background Evaluation of the cystic duct anatomy prior to cholecystectomy is important, to decrease the risk of bile duct injury. This study aimed to clarify the frequency of cystic duct variations and the relationship between them. Methods Data of 205 patients who underwent cholecystectomy after imaging at Sada Hospital, Japan, were analyzed. The...

Tumor antigens are crucial targets for T-cell-based therapy to induce tumor-specific rejection. However, identifying pancreatic ductal adenocarcinoma (PDAC)-specific T-cell epitopes has been challenging. Using advanced mass spectrometry (MS) analysis, we previously identified cancer-associated, class I MHC-bound epitopes shared by multiple PDAC pat...

Prediction of tumor-specific T cell epitopes is an important part of cancer immunotherapies. In the past, tumor-specific T cell epitopes were identified by mapping the epitopes on the known cancer-testis antigens and tumor-associated antigens or antigens that react to the T cells induced by the cancer vaccine therapy. More recently, in silico predi...

Background Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). Methods We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human...

Background: Tumor-associated antigens and neoantigens serve as primary targets for cancer immunotherapies such as vaccines and T-cell based therapy. However, identifying pancreatic ductal adenocarcinoma (PDAC) associated T-cell epitopes have been challenging due to its low genomic mutational burden. In this study, we attempted to directly identify...

The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed to the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti–PD-1 antibody (αPD-1); thus, we examined PDAC vaccine or radiation therapy (RT)...

Background Immunotherapy has demonstrated a limited clinical efficacy in approximately 5% of cholangiocarcinoma. The main challenges for an effective immunotherapy response in cholangiocarcinoma arise from the tumor microenvironment, which is poorly understood. Methods For a comprehensive analysis of the tumor microenvironment in cholangiocarcinom...

How tumor-associated macrophages transit from a predominant antitumor M1-like phenotype to a protumoral M2-like phenotype during the development of pancreatic ductal adenocarcinoma (PDA) remains to be elucidated. We thus conducted a study by employing a PDA-macrophage co-culture system, an “orthotopic” PDA syngeneic mouse model, and human PDA speci...

Background Metastasis occurs in the majority of pancreatic ductal adenocarcinoma (PDAC) patients at diagnosis or following resection. Patients with liver metastasis and those with lung metastasis have significantly different prognosis. Here, we sought to understand how cancer-associated fibroblasts (CAFs) play roles in the development of organ-spec...

Background The resistance of pancreatic ductal adenocarcinoma(PDAC) to immune checkpoint inhibitors(ICIs) is mainly attributed to the immune-quiescent nature of its tumor microenvironment(TME). Radiotherapy(RT) activates innate responses including the RAGE and TLR2/4 pathways and subsequently modifies the TME by promoting the release of chemokines...

Background Gallbladder polyps are relatively common. Although most gallbladder polyps are benign, some are malignant. Current guidelines state that malignancy should be suspected for polyps ≥ 10 mm in diameter. We clarified the cancer detection rates in accordance with the size distribution of gallbladder polyps, and evaluated the effectiveness of...

Background The preoperative distinction between uncomplicated and complicated appendicitis is important to determine the appropriate treatments, such as antibiotics, surgery, or interval appendectomy. Computed tomography (CT) plays an important role; however, combining clinical and imaging factors may make preoperative evaluation more reliable. Thi...

Background Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) we...

Metabolism is shifted toward glycolysis with increased glucose uptake in anti-tumor M1 macrophages, and toward oxidative phosphorylation with significant decreased glucose uptake in pro-tumor M2 macrophages in Pancreatic ductal adenocarcinoma (PDA). Current study aims to investigate the mechanism by which tumor cells reprogram tumor associated macr...

Pancreatic ductal adenocarcinoma (PDA) is a devastating disease, with the lowest stage-combined 5-year survival rate of any cancer type at 8%. One major attribute for this poor prognosis is the lack of effective treatments in preventing and controlling metastasis. Previously, our lab has identified the secreted protein Semaphorin3D (Sema3D) to be i...

Metabolism is shifted toward glycolysis with increased glucose uptake in anti-tumor M1 macrophages, and toward oxidative phosphorylation with significant decreased glucose uptake in pro-tumor M2 macrophages in Pancreatic ductal adenocarcinoma (PDA). Current study aims to investigate the mechanism by which tumor cells reprogram tumor associated macr...

Background & aims: Little is known about mechanisms of perineural invasion (PNI) by pancreatic ductal adenocarcinomas (PDAs) or other tumors. Annexin A2 (ANXA2) regulates secretion of SEMA3D, an axon guidance molecule, which binds and activates the receptor PLXND1 to promote PDA invasion and metastasis. We investigated whether axon guidance molecu...

A dextran-peptide conjugate was developed for MR molecular imaging of pancreatic ductal adenocarcinoma (PDAC) through its overexpressed microenvironment biomarker, extradomain-B fibronectin (EDB-FN). This new agent consists of diamagnetic and biocompatible dextran and a targeting peptide. Dextrans can be directly detected by chemical exchange satur...

Pancreatic ductal adenocarcinoma (PDA) is a devastating malignant disease. Upon diagnosis, eighty percent of patients present with metastatic disease. Perineural invasion, the spreading of cancer to the space surrounding or invading the nerve, is often found in surgically removed pancreatic tumors and is associated with a worse overall prognosis in...

The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinom...

Stromal fibrosis is a prominent histological characteristic of pancreatic ductal adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor microenvironment (TME) to support tumor growth is largely unknown. Here we show that PDAC cells can induce DNA methylation in cancer associated fibroblasts (CAF). Upon direct contact with PDA...

The cell surface protein Transmembrane 4 L6 family member 1 (TM4SF1) has been detected in various tumors, and its expression on tumor cells is implicated in cancer cell metastasis and patient prognosis. The role of TM4SF1 in malignant tumors remains poorly understood, particularly in pancreatic cancer. We performed immunohistochemical staining to a...

Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of...

Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs...

Improving poor outcomes in patients with pancreatic cancer requires a greater understanding of the biological mechanisms contributing to radioresistance. We, therefore, sought to identify genes involved in the radioresistance of pancreatic cancer cells. Two pancreatic cancer cell lines, CFPAC-1 and Capan-1, were repeatedly exposed to radiation, est...

Pancreatic cancer is associated with a devastating prognosis, partially because of its aggressive metastatic ability. Identification of prognostic markers of metastasis would be useful in the clinical management of postoperative patients with pancreatic cancer. Mal, T-cell differentiation protein 2 (MAL2) has been identified as a molecule predictiv...

Objective: To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes. Background: Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, h...

Pancreatic stellate cells (PSCs), which are implicated in desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress desmoplasia and exert anti-tumor effects against pancreatic cancer. Primary PSCs were established...

Clinicopathological characteristics of the patients (n = 105). (DOCX)

Univariate survival analyses for conventional prognostic factors and stromal CD271 expression (n = 105). (DOCX)

Background: Pancreatic cancer (PC), a hypovascular tumor, thrives under hypoxic conditions. Pancreatic stellate cells (PSCs) promote PC progression by secreting soluble factors, but their functions in hypoxia are poorly understood. This study aimed to clarify the effects of hypoxic conditions on the interaction between PC cells and PSCs. Methods:...

Extracellular matrix (ECM) remodeling is predominantly mediated by fibroblasts using intracellular and extracellular pathways. Although it is well known that extracellular degradation of the ECM by proteases derived from cancer cells facilitates cellular invasion, the intracellular degradation of ECM components by cancer cells has not been clarifie...

Background/aims: Although adjuvant chemotherapy (AC) using gemcitabine improves the prognosis of patients with resectable pancreatic cancer, the effect of gemcitabine AC on the prognosis of patients with borderline resectable pancreatic cancer is not clear. Methodology: We analyzed the prognosis of patients with pancreatic cancer who underwent c...

We report a case of undifferentiated colon cancer treated with FOLFIRI therapy. A 69-year-old male had suffered from descending colon cancer. He underwent a left hemicolectomy with D3 dissection. Histopathologically, the tumor was undifferentiated carcinoma, and the cytology of ascites was positive. Peritoneal disseminations occurred soon after sur...

Background/aims: Single-incision laparoscopic cholecystectomy (SILC) is a promising alternative to standard multi-incision laparoscopic cholecystectomy (LC). However, generalization of SILC is still hampered by technical difficulties mainly associated with the lack of trocars used for retraction of the gallbladder. We therefore developed a modifie...

肝嚢胞は日常診療においてよく遭遇する病変で，通常無症状に経過し臨床的に問題となることは少ない．今回，われわれは幽門輪温存膵頭十二指腸切除術（PpPD）後に，肝嚢胞に感染を生じた2例を経験した．1例目は77歳男性で，膵頭部癌に対する術後1年3カ月に発熱および腹痛が出現し，CT所見によって感染性肝嚢胞と診断，2例目は75歳女性で膵管内乳頭粘液性腺腫に対するPpPD術後2カ月で肝嚢胞感染を発症した．いずれの症例も抗生剤投与および経皮経肝膿瘍ドレナージで治癒した．肝嚢胞を有する症例で胆道再建を行った際は，胆管炎のみならず嚢胞感染を生ずる可能性を念頭において経過観察する必要があることが示唆された．

Aberrant pancreas in the jejunum is a rare condition, and its malignant transformation is very unusual. We presented a case in which jejunal carcinoma occurred in the aberrant pancreas. A 76-year-old woman was admitted to our hospital due to repetitive vomiting after meals. Radiology showed high obstruction in the proximal jejunum. Laparotomy revea...