Herbal extracts that induce type I interferons through Toll-like receptor 4 signaling.

BACKGROUND: A mixture of five herbal extracts called internatural (INT), which is prepared from pumpkin seeds, purple turmeric, pearl barley, corn pistil, and cinnamon, is widely used by people in Japan and elsewhere for its immunity-enhancing effects and general health. Although anecdotal evidence indicates its efficacy, the mechanisms by which INT boosts immunity have remained unknown. OBJECTIVE: The aim of this study was to investigate whether INT induces type I interferons (IFNs) in murine bone marrow-derived macrophages (BMDMs) and by what mechanism. DESIGN: We measured induction of type I IFNs (IFNß and IFNα) in BMDMs treated with INT or other Toll-like receptor ligands: bacterial lipopolysaccharides (LPS), dsRNA, poly(I:C), and CpG oligonucleotides. To investigate whether INT signals through Toll-like receptor 4 (TLR4), we tested TLR4-specific inhibitor. We also tested if INT utilizes TLR4 adaptors, toll/IL-1 receptor (TIR) domain-containing adaptor (TRIF), or myeloid differentiation factor 88 (MyD88), we examined INT induction of IFNß in TRIF-KO and MyD88-KO BMDMs. We then investigated whether INT provides an antiviral effect upon fibroblasts either directly or indirectly using the encephalomyocarditis virus (EMCV) model. RESULTS: We first observed that INT, when added to BMDMs, potently induces type I IFNs (IFNß and IFNα) within 2 h. INT induction of IFN expression was mediated by TLR4, which signaled through the TRIF/MyD88 adaptors, similar to LPS. A high-molecular-weight fraction (MW > 10,000) of INT extracts contained IFN-inducing activity. Supernatants from INT-treated BMDMs protected untreated fibroblast from EMCV infection as reduced viral titers. CONCLUSIONS: INT induced type I IFN mRNA and proteins in BMDMs and other cell types. This induction was mediated by TLR4, which transduces signals using the TRIF/MyD88 pathway. The high-MW component of INT contained type I IFN inducing activity. The supernatants from INT-treated cells displayed antiviral activity and protected cells from EMCV infection. These findings indicate that INT is a novel natural IFN inducer that strengthens host's innate immunity.

Nanoparticle formation in Au thin films by electron-beam-induced dewetting.

We carried out investigations on electron-beam-induced nanoparticle formation in thin (5-30 nm) Au films on smooth SiO(2)/Si substrates. When the Au films were irradiated with an electron beam, the Au films broke up into nanoparticles through the dewetting process. The dominant wavelengths of the surface (corresponding to the pitch between nanoparticles) were closely related with the thickness of the Au. We then developed a new technique for the formation of periodically arranged Au nanoparticles using a holed substrate. The nanoholes induced heterogeneous nucleation and helped to form ordered nanoparticles between the holes. Two-dimensionally, periodically arranged Au nanoparticles with a pitch of 100 nm were obtained.

[A case of non-small cell lung cancer in which complete response was achieved with chemotherapy including cisplatin, vinorelbine, mitomycin C, followed by additional cisplatin, etoposide and concurrent radiotherapy].

A 43-year-old man presented at our hospital with a complaint of cough and sputum. A plain chest X-ray and CT scan revealed a tumor shadow 8 cm in size in the right hilar and enlarged mediastinal lymph node. The tumor had invaded the superior vena cava. A tumor biopsy done under bronchoscopy revealed poorly-differentiated adenocarcinoma (cT4N2M0). He was given three courses of a combination therapy consisting of cisplatin (80 mg/m(2)), vinorelbine (25 mg/m(2)) and mitomycin C (8 mg/m(2)). Additionally, concurrent chemoradiotherapy (cisplatin 80 mg/m(2)+etoposide 100 mg/m(2), and 45 Gy) was performed. Right pneumonectomy was performed, because the primary tumor and the enlarged lymph node were markedly reduced in size, and a histological examination of the resected specimen revealed no detectable cancer cells.

[Successful treatment with etoposide by oral administration for recurrence of gastric diffuse large B-cell lymphoma after surgical resection--a case report].

A 64-year-old woman, who had been treated for gastric diffuse large B-cell lymphoma (DLBCL) by total gastrectomy and received 3 courses of CHOP therapy at 61 years of age, was diagnosed with recurrence of DLBCL in the small intestine. After the small intestinal tumor was resected, multiple metastases were found in the liver. Because intensive chemotherapy was difficult for her poor performance status, 50 mg of etoposide daily by oral was administered for 21 consecutive days. After one course of chemotherapy, liver metastases and lymph node swelling almost disappeared without severe adverse effects, and after five courses she achieved complete remission. Though DLBCL invaded the central nervous system, the abdominal regions had been free from recurrence for 12 months. This case report suggests that oral etoposide therapy is useful for gastrointestinal DLBCL which has metastasized to the liver.

Magnitude of combination therapy of radical resection and external beam radiotherapy for patients with carcinomas of the extrahepatic bile duct and gallbladder.

The present study sought to identify the therapeutic efficacy of adjuvant external beam radiotherapy (EBRT) for carcinomas of the extrahepatic bile duct (EHBD) and gallbladder. Twenty-one patients with pathologically verified EHBD carcinoma and 18 patients with gallbladder carcinoma were analyzed retrospectively by Cox regression analysis for predictors of survival. The overall 5-year survival rates after resection were 33% for EHBD carcinoma and 56% for gallbladder carcinoma. The overall 5-year survival rate for EHBD carcinoma was 60% in 8 patients without microscopic residual disease (R0), 15% in 9 patients with microscopic residual tumor (R1), and 0% in 4 patients with macroscopic residual tumor (R2). The overall 5-year survival rate of gallbladder carcinoma patients was also decreased with R status equal to 73%, 40%, and 0% for R0, R1 and R2, respectively. Adjuvant radiotherapy significantly improved the 5-year survival rate in 7 patients with R1 disease of EHBD carcinoma (P = .035), compared with survival in 2 patients who underwent resection alone. However, no significant difference was noted in the 5-year survival rate between the resection plus EBRT group and the resection alone group for gallbladder carcinoma. Multivariate analysis revealed that histopathologic grade (G) was an independent predictor of survival for EHBD carcinoma and that direct invasion of liver parenchyma was a predictor of survival for gallbladder carcinoma. This study suggests that curative resection provides the best survival for patients with EHBD and gallbladder carcinoma, and that radiotherapy may play a beneficial role in controlling local-regional residual EHBD carcinoma tumors. However, new strategies for adjuvant therapy are needed to improve survival in patients with gallbladder carcinoma.

An open-label study of administration of EH0202, a health-food additive, to patients with chronic hepatitis C.

BACKGROUND: In this study, we examined the effect of EH0202, a mixture of four herbal extracts that are known to induce interferons, on hepatitis C virus (HCV)-RNA levels in patients with chronic hepatitis C. METHODS: This was an open-label uncontrolled study. The study subjects ingested food containing EH0202 daily for 3 months, which was equivalent to 1 g of desiccated herbs daily. Clinical symptoms, hematology and biochemical examinations, urine, and HCV-RNA levels were examined before, during (1 month), and after the EH0202 treatment (3 months). RESULTS: Among the 35 patients who successfully completed the study, there were improvements in malaise (seen in 6 patients before and in 2 after EH0202 treatment), bloating sensation in the abdomen (seen in 2 before and in none after treatment), and nausea and vomiting (seen in 2 before and in 1 after treatment). There were no changes in hematology or biochemical examination parameters. There was a statistically significant decrease in HCV-RNA levels in patients with high viral titers after 3 months of EH0202 administration. No serious adverse events were observed with the EH0202 treatment. CONCLUSIONS: These findings suggest that EH0202 may be safe and useful in the treatment of patients with chronic hepatitis C. Further studies are, however, needed to obtain a definitive conclusion.

[Effects of radiation therapy for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer].

Effects of radiation therapy for lymph node metastases from gastric cancer were retrospectively analyzed. The radiation sites were residual paraaortic lymph node involvement and postoperative recurrent lymph node metastases in 10 patients. The size of lymph node swelling was decreased in 6 (60%) patients after radiation therapy using liniac. Complaints due to lymph node metastases such as pain and edema of extremities were voiced by 7 patients. These complaints were eventually relieved or disappeared in all 7 patients. There were no severe adverse effects during radiation therapy, and 7 patients (70%) could shift to home care. One-year and 3-year survival rates were 20 and 10%, respectively. Radiation therapy for lymph node metastases from gastric cancer was chiefly effective in relieving complaints. Although it is unclear whether radiation therapy can improve the survival rate, these results suggest that radiation therapy could be one of the most useful locoregional therapies for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer.

[Perioperative management of patients with idiopathic thrombocytopenic purpura].

Patients suffering from idiopathic thrombocytopenic purpura(ITP) who undergo surgery may have an increased risk of postoperative bleeding complications. In general, bleeding is a regular occurrence when the platelet count is less than 30,000 to 50,000/mm3. Therefore, high-dose immunoglobulin therapy and transfusion of platelet concentrates are used to increase the platelet count immediately before operation. In our experience of 3 patients undergoing operations, preoperative management was performed by these methods and platelet concentrates were transfused during and after surgery. No difficulty was encountered with hemostasis and the postoperative course was uneventful in all 3 patients. In patients with ITP, adequate perioperative management, such as high-dose immunoglobulin and platelet transfusion allows surgical treatment to be performed safely and successfully.

Primary hepatic leiomyosarcoma in a woman after renal transplantation: report of a case.

In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including leiomyosarcoma are rarely associated with transplant recipients. We herein present a 33-year-old woman with end-stage renal disease who received a transplant at 27 years of age. Four years after the transplantation, at age 31, she underwent a mastectomy because of primary right breast cancer, which was found to be a 5-mm-sized mucinous carcinoma with no regional lymph node metastasis. Six years after the transplantation, a liver tumor was unexpectedly discovered. An explorative laparotomy revealed a well-encapsulated tumor occupying the posterior portion of the right lobe of the liver. The patient underwent a posterior segmentectomy. Histologically, the tumor possessed intermingling fascicles of spindle cells with eosinophilic cytoplasm and elongated nuclei. Based on an immunohistochemical examination, the tumor cells were positive for the muscle-associated antibody. In addition, RNA probes for Epstein-Barr virus were negative based on in situ hybridization. The histologic, immunohistochemical findings were considered to be diagnostic for leiomyosarcoma, which is a low-grade malignancy. Two years after surgery, the patient is doing well with no recurrence of liver tumors or breast cancer.

Massive hemorrhage in a patient with intestinal Behçet's disease: report of a case.

Major gastrointestinal bleeding is a rare manifestation of intestinal Behçet's disease. We report herein the case of a 64-year-old man with intestinal Beh,et's disease complicated by myelodysplastic syndrome who suffered massive hemorrhage. Colonoscopy demonstrated ulceration of the entire colon from the cecum to the rectum, characterized by punched-out ulcers. Angiography demonstrated apparent extravasation of contrast material in the terminal ileum, and embolization was not successful. Continued and massive bleeding necessitated surgical resection of the involved segment of ileum; however, massive bleeding recurred. Re-endoscopy showed oozing hemorrhage from the multiple colon ulcerations. Intra-arterial prednisolone injection therapy was given, following which the melena gradually subsided and completely stopped within a few days.

[A case of stage IV gastric carcinoma with lymph nodes metastases of the paraaorta responding markedly to TS-1].

A 64-year-old man had undergone subtotal gastrectomy with a D2 lymphadenectomy for advanced carcinoma of the stomach with paraaortic lymph nodes metastases 12 months earlier. The histopathological findings revealed a well differentiated adenocarcinoma [type 2 macroscopic findings, SE, INF beta, ly2, v1, N2, M1 (LYM)]. On admission, biochemical investigations showed an elevation of CEA, CA19-9, and CA 125. An abdominal ultrasonography and a computed tomography (CT) revealed lymph node swelling of the paraaorta. After non-curative operation, he has received adjuvant chemotherapy with TS-1 plus CDDP. At first, 100 mg/day of TS-1 was orally administered for three weeks followed by two drug-free weeks, with CDDP (60 mg/m2/day) infused on day 8. Next, the treatment course consisted of four-week consecutive administration of TS-1 (80 mg/day) followed by two drug-free weeks, with biweekly infusion of CDDP at a dose of 15 mg/m2. The CT findings revealed that an almost complete reduction of the metastatic paraaortic lymphnodes was obtained after completion of course 1, and was maintained thereafter. No noteworthy adverse reactions were observed and the patient has a good QOL. The patient is now in a good health and continues to undergo low dose TS-1 plus CDDP chemotherapy as an outpatient.