Suppressive effects of transforming growth factor-beta1 produced by hepatocellular carcinoma cell lines on interferon-gamma production by peripheral blood mononuclear cells.

Transforming growth factor-beta1 (TGF-beta1) exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma (HCC) cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay (ELISA), we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF-beta1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)-gamma induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7 +/- 0.8, 17.3 +/- 9.0, and 35.9 +/- 14.6%, respectively, compared with the value in the culture with control medium (complete culture medium). These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, and thus could enhance their ability to escape immune-mediated surveillance.</p

A study of the compound evaluation for geophysical explorations by self-organizing maps

In Japan, in the high economic growth period in 1960’s, a great number of cutting ground and embankment slopes were formed to construct many roads. They have been aging now, it is important to estimate the health of them and maintain effectually. So, in situs, we usually carry out many kinds of the geophysical exploration. However, there is not the technique to compound and interpret the result of each geophysical exploration in a numerical formula of the engineering now. Therefore, we notice to self-organizing maps (SOM) used widely in a field of the information processing engineering, and tried to interpret multidimensional data by integrating. In this paper, we classified the ground property by SOM. The classification result is relatively conformal with boring data. Therefore, it is recognized that it can be used to improve the interpretative accuracy of compound geophysical explorations.12th ISRM International Congress on Rock Mechanics "Harmonizing Rock Mechanics and the Environment" 18-21 October 2011, Beijing, Chin

Therapeutic effects of azathioprine in combination with low-dose prednisolone in patients with intractable autoimmune hepatitis type 1.

This study evaluated the effects of azathioprine in combination with low-dose prednisolone in the management of patients with intractable autoimmune hepatitis. Thirteen patients with intractable autoimmune hepatitis who had an incomplete or arrested response to conventional prednisolone therapy, or who relapsed during prednisolone maintenance therapy were additionally administered 50 or 100 mg/day of azathioprine in combination with prednisolone. This regimen reliably induced complete remission in 12 of 13 patients, and these 12 remained in remission during the follow-up period with maintenance therapy of 50 mg/day of azathioprine in combination with 5 mg/day of prednisolone. The findings of the current study indicate that the azathioprine and low-dose prednisolone combined therapy may offer a satisfactory alternative therapy for patients with intractable autoimmune hepatitis who have an incomplete or arrested response to conventional prednisolone therapy, or who relapse during prednisolone maintenance therapy.</p

Pregnant women's awareness of sensitivity to cold (hiesho) and body temperature observational study: A comparison of Japanese and Brazilian women

<p>Abstract</p> <p>Background</p> <p>Sensitivity to cold (<it>hiesho</it>) is a serious health problem in Japan, yet it is minimally understood within Western cultures. The purpose of this study was to clarify the divergence between pregnant Japanese woman living in Japan and pregnant Brazilian women living in Brazil in awareness of <it>hiesho </it>and differences between core body and peripheral temperatures.</p> <p>Methods</p> <p>The subjects of this study were 230 pregnant Japanese women living in Japan and 200 pregnant Brazilian women living in Brazil. Data was collected in June/July and November 2005 in Japan and from October 2007 to February 2008 in Brazil. The survey methods consisted of measurement of deep body temperatures and questionnaires.</p> <p>Results</p> <p>67.0% of Japanese women and 57.0% of Brazilian women were aware of <it>hiesho</it>, which showed a significant difference between the Japanese and Brazilian women (p = 0.034). The difference between forehead and sole temperatures was 2.0°C among Japanese and 2.8°C among Brazilians in June-July (p = 0.01). But in November the difference between those temperatures was 5.2°C among Japanese and 2.8°C among Brazilians (p < 0.001).</p> <p>Conclusions</p> <p>There are differences between Japanese and Brazilians both in awareness of <it>hiesho </it>and in body temperatures.</p

Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer

Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4–29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23–58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1–6.1 months) and 2.0 months (95% CI 1.2–3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted

Successful amnioinfusion for severe fetal growth restriction with umbilical cord complications: two case reports.

Background:There is no established treatment for fetal growth restriction during pregnancy. We report two cases that represent an example of an amnioinfusion-based management strategy for severe fetal growth restriction with umbilical cord complications.Case presentation:We encountered two cases of fetal growth restriction with abnormal fetal Doppler velocity. In one case, fetal ultrasound revealed a hypercoiled umbilical cord with a single umbilical artery and oligohydramnios, while fetal Doppler revealed a reversed end-diastolic flow in the umbilical artery and reversed a-waves of the ductus venosus. Umbilical cord compression was confirmed at 22 weeks and 2 days of gestation, and nine amnioinfusions were performed to relieve the umbilical cord compression. A cesarean section was performed at 31 weeks and 2 days of gestation because of severe preeclampsia. The Asian infant is now a normally developed 6-month-old. In another Asian case, fetal ultrasound revealed a hypercoiled cord, while fetal Doppler revealed a reversed end-diastolic flow in the umbilical artery and intermittent reversed a-waves of the ductus venosus. Umbilical cord compression was confirmed at 24 weeks and 5 days of gestation, and seven amnioinfusions were performed. A cesarean section was performed at 31 weeks and 1 day of gestation because of nonreassuring fetal status. At the age of 1 month, the Asian infant was stable on respiratory circulation. In both cases, fetal Doppler findings improved significantly following amnioinfusions.Conclusions:Amnioinfusion is a symptomatic treatment for umbilical cord compression. However, to determine the therapeutic effect of amnioinfusion, complete resolution of the umbilical cord compression should be ascertained by ultrasonography

IRIS plus panitumumab for metastatic CRC

Background Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. Methods Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥ 20 years. Patients received panitumumab (6mg/kg) and irinotecan (100mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9%) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7%), acne-like rash (13.9%), and neutropenia (11.1%). The overall RR was 33.3% (12/36). Of these 4 five underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI 3.5-15.4 months) and 20.1 months (95% CI 16.7-23.2 months), respectively. Conclusion IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC