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Eight bacterial strains were used in this study to examine the survival of intestinal bacteria in immune cell cultures under aerobic and anaerobic culture conditions. With the addition of penicillin G and streptomycin, viable

Crohn's disease (CD) development is thought to involve genetic factors related to immune response as well as environmental factors, such as intestinal bacteria and diet, though no clear cause has yet been identified. In our previous study, we found that the concentrations of linoleic acid, stearic acid, and metabolites in erythrocytes differed between CD patients and healthy subjects. These factors related to lipid metabolism are controlled by Δ6 desaturase (fatty acid desaturase 2, FADS2) and elongase 6 (ELOVL6), respectively. In the present study, we analyzed the gene sequences of FADS2 and ELOVL6 in 52 Japanese CD patients, and then compared mutation frequencies with findings in healthy individuals. Nineteen FADS2 mutations and 33 ELOVL6 mutations were found. Furthermore, a new variant in the promoter region was shown in both genes, though no mutation in the coding region was found in either. For the FADS2 intron, the allele frequency of rs227784 (0.3365; 95% CI = 0.0337-0.01460) was higher than that in healthy subjects (0.0190). Furthermore, allele rs227784 had a greater association with CD (odds ratio = 4.4; 95% CI = 2.1-9.3). As compared with healthy Japanese healthy individuals, no mutations were found with a largely deviated allele frequency in the present CD group. However, the number of patients examined was small, thus the reliability of our results is limited. The present findings regarding genetic effects on CD onset and lipid metabolism may be weak.

The associations of the immunological status of the pancreatic ductal adenocarcinoma (PDA) microenvironment with prognosis were assessed. A high tumor-infiltrating lymphocyte (TIL) density was associated with a better prognosis. Importantly, even with a high density of TILs, the PDA cells with programed cell death-ligand 1 (PD-L1) expression showed a worse prognosis than the patients with negative PD-L1 expression. A significant association between a better prognosis and a tumor microenvironment with a high TIL density/negative PD-L1 expression was observed. Assessments of a combined immunological status in the tumor microenvironment may predict the prognosis of PDA patients following surgical resection.

Supplemental Digital Content is available in the text., Background and aims Bacterial infections arising in patients with liver cirrhosis are associated with life-threatening complications such as hepatic encephalopathy and spontaneous bacterial peritonitis in relation to bacterial translocation. To investigate the state of bacterial translocation, we surveyed the peripheral blood microbiota by 16S rRNA gene sequencing and analysed the blood microbial profiles. Methods Sixty-six patients with liver cirrhosis were enrolled in this study, whereas 14 healthy individuals were also analysed as controls. Total RNA was purified from the peripheral blood, and an approximately 430 base pair genomic locus which included the V3-V4 region of the 16s rRNA gene was amplified and assessed using bacterial pyrosequencing. Results At the genus level, a total of 183 operational taxonomic units were identified in cirrhotic patients, whereas 123 units in controls. Intergroup differences in gut microbiota were analysed by the linear discriminant analysis effect size, which showed that the abundance of Enterobacteriaceae was significantly higher in cirrhotics. On the contrary, the abundance of Akkermansia, Rikenellaceae and Erysipelotrichales were significantly lower in cirrhotics (relative abundance of Akkermansia in cirrhotics and controls: 0% and 0.2%, respectively; Rikenellaceae: 0.1% and 0.92%; Erysipelotrichales: 0.58% and 1.21%). Conclusion The present study has demonstrated that various circulating bacteria are present in cirrhotic patients, and the diversity of such bacteria is consistent with the presence of dysbiosis in cirrhotics. Although the clinical significance of the findings remains to be clarified, the findings may potentially facilitate diagnostic and therapeutic attempts to comprehend and furthermore to manipulate bacterial infections in cirrhotic patients.

Characteristic bile duct and gut microbiota have been identified in patients with chronic biliary tract disease. This study aimed to characterize the fecal and bile microbiota in biliary tract cancer (BTC) patients and their relationship. Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were included. Ten healthy, age-matched subjects were also recruited for fecal microbiota comparison. The fecal and bile duct microbiotas were analyzed by sequencing the 16S rRNA gene V3-V4 region. Live bacteria were obtained in the bile from three BTC patients by culture, and metagenomics-based identification was performed. Linear discriminant analysis effect size showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Ten of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile were matched with the OTUs found in the BTC subject fecal samples. Furthermore, a bile-isolated strain possessed the carcinogenic bacterial colipolyketide synthase-encoding gene. Enterobacteriaceae was enriched in the BTC feces, and more than half of Enterobacteriaceae in the bile matched that in the feces at the OTU level. Our data suggests that fecal microbiota dysbiosis may contribute to BTC onset.

Background Characteristic bile duct and colonic microbiotas have been identified in patients with chronic biliary tract disease. Therefore, a characteristic microbiota is likely also formed in cholangio- and gallbladder carcinoma patients. This study aimed to characterize the faecal and bile microbiotas in biliary tract cancer (BTC) patients and their relationship to each other. Methods Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were prospectively included. Ten healthy, age-matched subjects were also recruited for faecal microbiota comparison. The colon and bile duct microbiotas were analysed by sequencing the 16S rRNA gene V3-V4 region. We also obtained live bacteria in the bile collected from three BTC patients by culture and performed metagenomics-based identification. Results The faecal microbiota composition differed in the BTC patients. Linear discriminant analysis (LDA) effect size (LEfSe) showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of butyrate-producing bacteria including Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Notably, 10 of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile samples were matched with the OTUs found in the BTC subject faecal samples. Further metagenomic approaches revealed a bile-isolated strain that possessed the carcinogenic bacterial colipolyketide synthase (PKS)-encoding gene. Conclusions Enterobacteriaceae was enriched in the BTC faeces. Taken together with the finding that more than half of Enterobacteriaceae in the bile matched that in the faeces at the OTU level, our data suggest that faecal microbiota dysbiosis possibly contributes to BTC onset.

Introduction Pericardial effusion is a rare complication of pancreatic cancer. We report a case of cardiac tamponade secondary to pancreatic cancer. Case presentation A 68-year-old Japanese man was diagnosed as having pancreatic cancer during surgery and received chemotherapy for 28 months after the diagnosis. He was admitted to the emergency room with severe dyspnea. Echocardiography revealed pericardial effusion with severe hypofunction. Emergency pericardial drainage was performed to maintain hemodynamics, which resulted in the elimination of 450 mL of blood and the maintenance of circulatory dynamics. Cytological examination of the pericardial fluid revealed atypical cells and tumor cells suggesting adenocarcinoma. Conclusions To our knowledge, pancreatic cancer complicated with cancerous pericarditis has not been previously documented. This case highlights the extreme severity of pericardial effusion, a sign of progressive disease, secondary to pancreatic cancer. In the case of neoplastic pericardial effusion, an extremely poor prognosis must be considered.

Background: We have developed a Wilms’ tumor 1 (WT1)-targeting dendritic cell (DC)-based cancer vaccine combined with standard chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDA). Methods: We evaluated predictive markers of overall survival (OS) in PDA patients treated with multiple major histocompatibility complex class I/II-restricted, WT1 peptide-pulsed DC vaccinations (DC/WT1-I/II) in combination with chemotherapy. Throughout the entire period of immunochemotherapy, the plasma levels of soluble factors derived from granulocytes of 7 eligible PDA patients were examined. Moreover, systemic inflammatory response markers (neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], and granulocyte-to-lymphocyte ratio [GLR]) were assessed. In addition, cytoplasmic WT1 expression in PDA cells was examined. Results: Compared to the 4 non-super-responders (OS Conclusions: Prolonged low levels of a granulocyte-related systemic inflammatory response after the early period of therapy and low cytoplasmic WT1 expression in PDA cells may be markers predictive of OS in PDA patients receiving WT1-targeting immunochemotherapy.

The aim of the present study was to investigate the efficacy of the actual consuming n-3 PUFA for remission-maintenance in IBD patients. A questionnaire on the dietary habits of patients one month before hospitalization (Q1) was completed by 24 patients with IBD (10 ulcerative colitis (UC) subjects and 14 Crohn’s disease (CD) subjects) treated at our hospital. We educated the study subjects about an n-3 PUFA diet, and a follow-up survey (Q2) was conducted 6 to 12 months after discharge. Disease activity was evaluated using the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and/or the Crohn’s Disease Activity Index (CDAI) score for CD and the partial UCDAI score without endoscopic evaluation for UC. Q1 showed that the average n-3 and n-6 PUFA intakes were 1673 ± 1651 mg and 9146 ± 5217 mg, respectively, and the average n-3/n-6 ratio was 0.27 ± 0.31. In Q2, the intake of n-3 PUFA was significantly higher (3671 ± 1684 mg, p < 0.001), whereas the n-6 PUFA intake decreased significantly (5217 ± 1973 mg, p < 0.001) compared to those in Q1. As a consequence, the dietary n-3/ n-6 ratio was significantly increased (0.87 ± 0.60, p < 0.001). Maintenance of the remission rate was significantly higher in IBD patients who complied with the n-3 diet, and these patients maintained a dietary n-3/n-6 ratio of 0.432 or higher (17 of 23 cases; 70.8%, p < 0.03) compared to that observed for IBD patients who did not comply with the diet. These results emphasize the importance of adjusting dietary PUFA and suggest that the n-3 diet may be effective in maintaining the remission of IBD.

Crohn's disease (CD) development is thought to involve genetic factors related to immune response as well as environmental factors, such as intestinal bacteria and diet, though no clear cause has yet been identified. In our previous study, we found that the concentrations of linoleic acid, stearic acid, and metabolites in erythrocytes differed between CD patients and healthy subjects. These factors related to lipid metabolism are controlled by Δ6 desaturase (fatty acid desaturase 2, FADS2) and elongase 6 (ELOVL6), respectively. In the present study, we analyzed the gene sequences of FADS2 and ELOVL6 in 52 Japanese CD patients, and then compared mutation frequencies with findings in healthy individuals. Nineteen FADS2 mutations and 33 ELOVL6 mutations were found. Furthermore, a new variant in the promoter region was shown in both genes, though no mutation in the coding region was found in either. For the FADS2 intron, the allele frequency of rs227784 (0.3365; 95% CI = 0.0337-0.01460) was higher than that in healthy subjects (0.0190). Furthermore, allele rs227784 had a greater association with CD (odds ratio = 4.4; 95% CI = 2.1-9.3). As compared with healthy Japanese healthy individuals, no mutations were found with a largely deviated allele frequency in the present CD group. However, the number of patients examined was small, thus the reliability of our results is limited. The present findings regarding genetic effects on CD onset and lipid metabolism may be weak.

Recent studies have suggested an association between certain members of the Fusobacterium genus, especially F. nucleatum, and the progression of advanced colorectal carcinoma (CRC). We assessed such an association of the gut microbiota in Japanese patients with colorectal adenoma (CRA) or intramucosal CRC using colonoscopy aspirates. We analyzed samples from 81 Japanese patients, including 47 CRA and 24 intramucosal CRC patients, and 10 healthy subjects. Metagenomic analysis of the V3-V4 region of the 16S ribosomal RNA gene was performed. The linear discriminant analysis (LDA) effect size (LEfSe) method was used to examine microbial dysbiosis, revealing significant differences in bacterial abundances between the healthy controls and CRA or intramucosal CRC patients. In particular, F. varium was statistically more abundant in patients with CRA and intramucosal CRC than in healthy subjects. Here, we present the metagenomic profile of CRA and intramucosal CRC and demonstrate that F. varium is at least partially involved in the pathogenesis of CRA and intramucosal CRC.

The only current curative treatment for patients with pancreatic ductal adenocarcinoma (PDA) is surgical resection, and certain patients still succumb to disease shortly after complete surgical resection. Wilms' tumor 1 (WT1) serves an oncogenic role in various types of tumors; therefore, in the present study, WT1 protein expression in patients with PDA was analyzed and the association with overall survival (OS) and disease-free survival (DFS) time in patients with PDA was assessed following surgical resection. A total of 50 consecutive patients with PDA who received surgical resection between January 2005 and December 2015 at the Jikei University Kashiwa Hospital (Kashiwa, Chiba, Japan) were enrolled. WT1 protein expression in PDA tissue was measured using immunohistochemical staining. Furthermore, laboratory parameters were measured within 2 weeks of surgery, and systemic inflammatory response markers were evaluated. WT1 protein expression was detected in the nucleus and cytoplasm of all PDA cells and in tumor vessels. WT1 exhibited weak staining in the nuclei of all PDA cells; however, the cytoplasmic expression of WT1 levels was classified into four groups: Negative (n=0), weak (n=19), moderate (n=23) and strong (n=8). In patients with PDA, it was demonstrated that the OS and DFS times of patients with weak cytoplasmic WT1 expression were significantly prolonged compared with those of patients with moderate-to-strong cytoplasmic WT1 expression, as determined by log-rank test (P=0.0005 and P=0.0001, respectively). Furthermore, an association between the density of WT1-expressing tumor vessels and worse OS/DFS times was detected. Multivariate analysis also indicated a significant association between the overexpression of WT1 in PDA tissue and worse OS/DFS times. To the best of our knowledge, the present study is the first to demonstrate that moderate-to-strong overexpression of WT1 in the cytoplasm of PDA cells is significantly associated with worse OS/DFS times. Therefore, overexpression of WT1 in the cytoplasm of PDA cells may impact the recurrence and prognosis of patients with PDA following surgical resection. The results further support the development of WT1-targeted therapies to prolong survival in all patients with PDA.

Several studies have suggested that an elevated neutrophil-lymphocyte ratio (NLR) is associated with a poorer prognosis in patients with pancreatic cancer (PC). The correlations between the NLR and immunohistochemical (IHC) analysis with regard to the prognosis of patients with PC remain to be elucidated. By using IHC findings, we determined the value of the NLR as a prognostic factor in patients with PC.We collected the clinico-pathological data of 28 consecutive patients who underwent surgical resection for PC between January 2008 and December 2012 at The Jikei University Kashiwa Hospital. We investigated whether the NLR and IHC results were related and ensured the consistency of the prognosis of patients with PC.The Kaplan-Meier curves for the disease-free survival (DFS) and the overall survival (OS) revealed that an NLR ≥ 5 is an implicit factor for decreased DFS and OS in patients with PC (p = 0.003, p 0.001, log-rank test). The density of CD163(+) macrophages and CD66b(+) neutrophils was significantly higher in the high NLR group; on the contrary, the density of CD20(+) lymphocytes was significantly higher in the low NLR group. Moreover, a Mann-Whitney U test showed that the NLR was significantly correlated with a high density of CD20(+) lymphocytes (p = 0.031) and CD163(+) macrophages (p = 0.023), while the NLR was not significantly correlated with CD66b(+) neutrophils (p = 0.397).Our results demonstrated the validity of the NLR by IHC analyses and we determined that a higher value of NLR is a trustworthy prognostic factor for patients with PC.

AIM: To investigate the association of plasma levels of interleukin (IL)-6 and -8 with Wilms’ tumor 1 (WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma (PDA) treated with dendritic cells (DCs) pulsed with three types of major histocompatibility complex class I and II-restricted WT1 peptides combined with chemotherapy. METHODS: During the entire treatment period, plasma levels of IL-6 and -8 were analyzed by ELISA. The induction of WT1-specific immune responses was assessed using the WT1 peptide-specific delayed-type hypersensitivity (DTH) test. RESULTS: Three of 7 patients displayed strong WT1-DTH reactions throughout long-term vaccination with significantly decreased levels of IL-6/-8 after vaccinations compared with the levels prior to treatment. Moreover, overall survival (OS) was significantly longer in PDA patients with low plasma IL-6 levels (< 2 pg/mL) after 5 vaccinations than in patients with high plasma IL-6 levels (≥ 2 pg/mL) (P = 0.025). After disease progression, WT1-DTH reactions decreased severely and were ultimately negative at the terminal stage of cancer. The decreased levels of IL-6/-8 observed throughout long-term vaccination were associated with WT1-specific DTH reactions and long-term OS. CONCLUSION: Prolonged low levels of plasma IL-6/-8 in PDA patients may be a prognostic marker for the clinical outcomes of chemoimmunotherapy.

A promising area of clinical investigation is the use of cancer immunotherapy to treat cancer patients. Dendritic cells (DCs) operate as professional antigen-presenting cells (APCs) and play a critical role in the induction of antitumor immune responses. Thus, DC-based cancer immunotherapy represents a powerful strategy. One DC-based cancer immunotherapy strategy that has been investigated is the administration of fusion cells generated with DCs and whole tumor cells (DC-tumor fusion cells). The DC-tumor fusion cells can process a broad array of tumor-associated antigens (TAAs), including unidentified molecules, and present them through major histocompatibility complex (MHC) class I and II pathways in the context of co-stimulatory signals. Improving the therapeutic efficacy of DC-tumor fusion cell-based cancer immunotherapy requires increased immunogenicity of DCs and whole tumor cells. We discuss the potential ability of DC-tumor fusion cells to activate antigen-specific T cells and strategies to improve the immunogenicity of DC-tumor fusion cells as anticancer vaccines.

Chondroitin sulfate E (CS-E), a highly sulfated glycosaminoglycan, is known to promote tumor invasion and metastasis. Because the presence of CS-E is detected in both tumor and stromal cells in pancreatic ductal adenocarcinoma (PDAC), multistage involvement of CS-E in the development of PDAC has been considered. However, its involvement in the early stage of PDAC progression is still not fully understood. In this study, to clarify the direct role of CS-E in tumor, but not stromal, cells of PDAC, we focused on carbohydrate sulfotransferase 15 (CHST15), a specific enzyme that biosynthesizes CS-E, and investigated the effects of the CHST15 siRNA on tumor cell proliferation in vitro and growth in vivo. CHST15 mRNA is highly expressed in the human pancreatic cancer cell lines PANC-1, MIA PaCa-2, Capan-1 and Capan-2. CHST15 siRNA significantly inhibited the expression of CHST15 mRNA in these four cells in vitro. Silencing of the CHST15 gene in the cells was associated with significant reduction of proliferation and up-regulation of the cell cycle inhibitor-related gene p21CIP1/WAF1. In a subcutaneous xenograft tumor model of PANC-1 in nude mice, a single intratumoral injection of CHST15 siRNA almost completely suppressed tumor growth. Reduced CHST15 protein signals associated with tumor necrosis were observed with the treatment with CHST15 siRNA. These results provide evidence of the direct action of CHST15 on the proliferation of pancreatic tumor cells partly through the p21CIP1/WAF1 pathway. Thus, CHST15-CS-E axis-mediated tumor cell proliferation could be a novel therapeutic target in the early stage of PDAC progression.

Azathioprine (AZA) is frequently used in patients with inflammatory bowel disease (IBD). However, toxic adverse reactions frequently develop and limit the clinical benefits. Currently, the precise mechanisms underlying thiopurine-related toxicity are not well understood. To investigate the relationship between the extent of thiopurine metabolism and adverse reactions in Japanese IBD patients, we prospectively observed 48 IBD patients who received AZA. We analyzed the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) gene mutations and measured the concentrations of 6-thioguanine nucleotide (6-TGN) continuously for 52 weeks. All patients possessed wild-type TPMT gene sequences. The ITPA 94C>A mutation was detected in 19 patients (39.6%). Adverse reactions developed in 14 of the 48 patients (29.2%), including leukopenia in 10 patients (20.8%). In the leukopenia group, the percentages of patients with 94C>A were higher than those in the without-leukopenia group (70.0% vs. 31.6%, P < 0.05). The average concentrations of 6-TGN in the patients with 94C>A were generally higher than those in the patients without 94C>A, however, there were no significant differences. Only 3 out of 10 patients with leukopenia exhibited high 6-TGN levels (30.0%). No negative correlations between white blood cell (WBC) counts and 6-TGN concentrations were observed. The cumulative incidence of leukopenia were higher for patients with 94C>A. Seven out of 19 patients (36.8%) with the ITPA 94C>A mutation developed leukopenia; however, this mutation may not unequivocally increase the risk of developing leukopenia. In addition, there are factors other than increased 6-TGN levels that are involved in the onset of leukopenia.

Some errors in Fig. 3B and Fig. 6C have been identified. The errors do not change the conclusion of the paper. The conclusion is supported by other figures in the paper, as well as results described in the text. The corrected Fig. 3B and Fig. 6C are shown below. [the original article was published in the International Journal of Oncology 45: 470-478, 2014 DOI: 10.3892/ijo.2014.2433]

The incidence of colorectal cancer (CRC) is on the rise, and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although chemotherapy and radiation therapy can improve survival rates, it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC. In this review, we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials, including peptide vaccines, dendritic cell-based cancer vaccines, whole tumor cell vaccines, viral vector-based cancer vaccines, adoptive cell transfer therapy, antibody-based cancer immunotherapy, and cytokine therapy. The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms.

Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.

The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.

Previous work has demonstrated that fusion cells generated from autologous monocyte-derived dendritic cells (MoDCs) and whole tumor cells induce efficient antigen-specific cytotoxic T lymphocytes. A major limitation to the use of this strategy is the availability of adequate amounts of autologous tumor cells. Moreover, MoDCs from cancer patients are often defective in their antigen-processing and presentation machinery. In this study, two types of allogeneic cells, a leukemia plasmacytoid dendritic cell (pDC) line (PMDC05) and pancreatic cancer cell lines (PANC-1 or MIA PaCa-2), were fused instead of autologous MoDCs and tumor cells. We created four types of pDC/tumor fusion cells by alternating fusion partners and treating with lipopolysaccharide (LPS): i) PMDC05 fused with PANC-1 (pDC/PANC-1), ii) PMDC05 fused with MIA PaCa-2 (pDC/MIA PaCa-2), iii) LPS-stimulated pDC/PANC-1 (LPS-pDC/PANC-1) and iv) LPS-stimulated pDC/MIA PaCa-2 (LPS-pDC/MIA PaCa-2) and examined their antitumor immune responses. The LPS-pDC/tumor cell fusions were the most active, as demonstrated by their: i) upregulated expression of HLA-DR and CD86 on a per-fusion-cell basis, ii) increased production of IL-12p70, iii) generation of a higher percentage of IFN-γ-producing CD4⁺ and CD8⁺ T cells and iv) augmented induction of MUC1-specific CD8⁺ T cells that lyse target tumor cells. This study provides the first evidence for an in vitro induction of antigen-specific cytotoxic T lymphocytes by LPS-stimulated fusion cells generated from leukemia plasmacytoid DCs and tumor cells and suggests that this strategy has potential applicability to the field of adoptive immunotherapy.

Duodenal diverticulum is a disease that clinicians commonly encounter in ordinary clinical work. Most cases are rarely regarded as clinical problems because of their asymptomatic progress. Among these cases, since Lemmel reported the clinical significance of juxtapapillary duodenal diverticula in 1934, describing them as Papillensyndrom, the effect of juxtapapillary duodenal diverticula on biliary-pancreatic diseases has been discussed due to the anatomical relationship of diverticula and the papilla of Vater. Although Lemmel syndrome’s frequency, impact on each disease and operative procedure have been reported in Japan, its clinical significance is still unclear. Until now, no guidelines regarding the therapeutic indication of juxtapapillary duodenal diverticula have been established, so a suitable therapeutic strategy needs to be selected for each patient. Here, we report a case of 60-year-old Japanese woman who repeatedly developed acute cholangitis and pancreatitis in a short period due to Lemmel syndrome, which was comprehensively diagnosed based on various imaging findings.

To examine whether commensal bacteria are a contributing cause of stress-related mucosal inflammation.Human peripheral blood monocyte-derived dendritic cells (MoDCs) were stimulated by commensal bacterial strains, including Escherichia coli, Clostridium clostridioforme, Bacteroides vulgatus (B. vulgatus), Fusobacterium varium (F. varium), and Lactobacillus delbrueckii subsp. bulgaricus. After incubation, corticotropin-releasing factor (CRF) and urocortin 1 (UCN1) mRNA in the cells was examined by real-time reverse transcription polymerase chain reaction. Supernatants from the cells were tested for CRF and UCN1 using an enzyme-linked immunosorbent assay.Both CRF and UCN1 were significantly augmented by B. vulgatus and F. varium at both the mRNA and protein levels. In particular, B. vulgatus stimulated human MoDCs, resulting in extremely high levels of CRF and UCN1.Stimulation of MoDCs by B. vulgatus and F. varium may be associated with CRF/UCN1-related intestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease.