Ryuichi Furuta

Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease

BackgroundWe investigated the possible roles of the interleukin (IL)-15 and IL-15 receptor (IL-15R) system in a heightened state of B-cell activation and differentiation in intestinal mucosa with inflammatory bowel disease (IBD).MethodsThe expression of IL-15 and IL-15Rα mRNA and protein in inflamed colonic mucosal tissues with IBD, and in control tissues was examined by reverse transcriptase-polymerase chain reaction and immunohistological methods. The effects of recombinant (r)IL-15 on the expression of IL-15Rα on lamina propria B cells and the production of immunoglobulin G (IgG) were analyzed in vitro, using lamina propria mononuclear cells (LPMCs) isolated from control tissues.ResultsThe intensity of IL-15 and IL-15Rα mRNA was greater in the mucosal tissues of patients with IBD, especially in those of patients with ulcerative colitis (UC), than in control tissues. Compared to control tissues, mononuclear cells positive for IL-15Rα protein were observed in greater proportions in tissue sections from patients with IBD, especially in those from patients with UC, where IL-15Rα protein was localized to CD20-positive B cells to a significant degree. There were increases in the proportions of IL-15Rα-positive B cells and IgG-producing cells in rIL-15- or rCD40L-stimulated cultures of LPMCs, with stimulatory effects being greater in the presence of their combination.ConclusionsThese data suggest that the IL-15 and IL-15R system may play important roles in the activation and differentiation of lamina propria B cells in patients with IBD, especially in those with UC.

Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis

Background:  The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well‐established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2‐(4‐chlorobenzoylamino)‐3[2‐(1H)‐quinolinon‐4‐yl] propionic acid}, a cytoprotective agent, has been reported to have anti‐inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients.

Lentinan prolonged survival in patients with gastric cancer receiving S-1-based chemotherapy.

AIM To examine whether administration of lentinan, purified β-1, 3-glucan, can prolong survival in advanced gastric cancer patients receiving S-1-based chemotherapy. METHODS Since 2004, 78 patients with metastatic or recurrent gastric cancer have received S-1-based chemotherapy as first-line treatment. Survival, side effects, and the ratio of granulocytes/lymphocytes (G/L ratio) were compared between 2 groups of patients who received chemo-immunotherapy using lentinan and chemotherapy alone. RESULTS Median overall survival was significantly longer in the former group than in the latter group [689 d (95% CI: 431-2339 d) vs 565 d (95% CI: 323-662 d), P = 0.0406]. In addition, the G/L ratio in patients who received lentinan was maintained around or below 2, which was significantly lower than that in patients who received chemotherapy alone (P < 0.001). CONCLUSION Chemo-immunotherapy with lentinan offers a significant advantage over S-1-based chemotherapy alone in terms of survival in patients with advanced gastric cancer.

Predictors of a response to cyclosporine or leukocyte removal therapy in patients with refractory ulcerative colitis

Introduction: Despite decades of clinical experience in optimizing the induction and maintenance of remission in patients with ulcerative colitis (UC), some patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side‐effects. We investigated factors predictive of the efficacy of cyclosporine and leukocyte removal therapy in patients with intractable UC.

Chemo-Immunotherapy Using Lentinan for the Treatment of Gastric Cancer with Liver Metastases

Gastric cancer is the third leading cause of cancer-related mortality worldwide. Systemic chemotherapy is the main treatment option for advanced gastric cancer when the tumor is inoperable. Despite recent advances in chemotherapeutic agents, the prognosis of unresectable or recurrent gastric cancer remains extremely poor. In Japan, combination therapy including S-1 and cisplatin is the standard first-line treatment for advanced gastric cancer; however, the five-year survival rate remains very low. Lentinan, the backbone of beta-(1,3)-glucan with beta-(1,6) branches, an active ingredient purified from Shiitake mushrooms, has been approved as a biological response modifier for the treatment of gastric cancer. This agent has been used in combination with oral fluoropyrimidines to improve the overall survival of gastric cancer patients. A retrospective chart review on 138 metastatic gastric cancer patients receiving chemotherapy was performed in Nagoya Memorial Hospital from 1 September 2010 to 31 August 2015. 12 patients with liver metastases were treated by lentinan in combination with S-1-based chemotherapy. The rate of objective response was 42% (5/12) and the disease control rate was 83% (10/12) in response to chemo-immunotherapy using lentinan, with a median overall survival of 407 days (95% CI: 207–700 days).

Primary Cutaneous Diffuse Large B-Cell Lymphoma with TongueInvolvement

We report a case of diffuse large B-cell lymphoma involving the thigh skin and tongue in an 85-year-old woman. No systemic symptoms or other lesions were observed at diagnosis. Local radiotherapy was effective, but cutaneous recurrence occurred 6 months after the treatment. The patient died of old age with no macroscopically distinguishable nodal or systemic lesions. A postmortem examination revealed intravascular invasion into the tongue, lung, and lymph nodes around the pancreas. To our knowledge, this is the first report of primary cutaneous diffuse large B-cell lymphoma with tongue involvement.

Infliximab regulates lamina propria T lymphocytes in patients with Crohn's disease: INFLIXIMAB AND CROHN'S DISEASE

The immune system is a major determinant of the pathophysiological inflammation, which may lead to gastrointestinal mucosal injury in patients with Crohns disease. Cytokines such as tumour necrosis factor‐alpha are well‐known mediators of the immune system, and treatment with a chimeric anti‐tumour necrosis factor‐alpha antibody (infliximab) has been shown to be highly effective in patients with Crohns disease. Recent evidence indicates that infliximab induces apoptosis in lamina propria T lymphocytes in these patients. To better understand the mechanisms of infliximabs effect on gastrointestinal inflammation, we investigated changes in the serum level of cytokines after treatment in these patients, and the effect of infliximab in inducing the apoptosis of T lymphocytes.

Effects of Oral Rinse using Lemon-Flavored Water with or without Rebamipide on Fluoropyrimidine-Induced Stomatitis

Aim: To examine the efficacy of oral rinsing against chemotherapy-induced stomatitis. Methods: Consecutive fluoropyrimidine-treated patients with stomach and colorectal cancer were enrolled from April 2009 to March 2011 (n=43; Group 1) and from January 2012 to December 2012 (n=45; Group 2). The incidence and severity of stomatitis were compared between Group 1 patients, who were instructed to gargle with lemonflavored water 6 times daily, and Group 2 patients, who did not receive any specific guidance. Among patients in the gargle group, we determined the rate of gargling compliance as well as quality of life (QOL) scores, and evaluated the impact of rebamipide use on patient outcomes. Results: The incidence of stomatitis was significantly reduced in Group 1 (14.0%) compared to that in Group 2 (33.3%) and its severity in the former group was milder. Among patients using lemon-flavored water, concomitant rebamipide use had no statistically significant impact on stomatitis incidence (with versus without rebamipide, 19.0% versus 9.0%), the rate of gargling compliance (96.4% versus 94.2%), or QOL scores. Conclusions: Oral rinse with lemon-flavored water is useful for the symptomatic control of fluoropyrimidineinduced stomatitis, regardless of the presence or absence of rebamipide.

Lentinan, A Shiitake Mushroom ò-Glucan, Stimulates Tumor-Specific Adaptive Immunity through PD-L1 Down-Regulation in Gastric Cancer Cells

Background: Despite the significant advances in chemotherapy, the prognosis of unresectable gastric cancer is still very poor and the role of immunotherapy remains to be clarified. We examined whether lentinan, a biological response modifier, could enhance the chemotherapeutic effects. Materials and methods: A retrospective cohort study was conducted to evaluate the survival benefits of lentinan among the patients with gastric cancer receiving chemotherapy. To investigate the mechanisms underlying the clinical effects of lentinan, its cytotoxic activity was accessed by cell proliferation assay. The expression of molecules relevant to immune checkpoints were analyzed by real-time PCR using human gastric cancer cell lines; MKN1, MKN45, and NUGC3. Results: The addition of lentinan prolonged the survival of patients with gastric cancer receiving S-1 based chemotherapy. Lentinan reduced the constitutive expression of PD-L1 in all cell lines mainly by suppressing the MAPK pathway. Conclusion: Lentinan at clinical concentrations stimulates tumor-specific adaptive immunity through PD-L1 downregulation, which may enhance chemotherapy-induced tumor clearance and patient survival.

A Case of Sigmoid Colon Cancer in which Somatic Pain was Rapidly Alleviated after Panitumumab Administration Despite Tumor Progression

We present a 72-year-old woman with sigmoid colon cancer in whom the somatic pain was alleviated rapidly after the administration of anti-epidermal growth factor antibodies. Our patient had received 4 cycles of FOLFIRI therapy (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab (Pmab) for the treatment of unresectable primary cancer accompanied with multiple liver metastases and peritonitis carcinomatosa. As grade 3 paronychia eventually occurred, chemotherapy was stopped. After recovery of the grade 3 paronychia, Pmab was re-introduced and administered every alternate cycle to reduce the extent of adverse events. The patient had complained of somatic pain in the lower right abdomen just before re-initiating Pmab administration. The pain intensity decreased immediately after the administration of Pmab. On the next day her pain had remarkably alleviated and she was free from pain for a week. This phenomenon was repeatedly observed. After the re-introduction of Pmab, tumor response was evaluated on computed tomography, which showed progressive disease. We demonstrated that Pmab was effective in the alleviation of somatic pain, although the size of the tumors gradually increased.