The inhibitory effect of heat treatment against epithelial-mesenchymal transition (EMT) in human pancreatic adenocarcinoma cell lines

Epithelial-mesenchymal transition (EMT) plays a crucial role in cancer metastasis. In this study, we evaluated the effect of heat treatment on tumor growth factor-β1 (TGF-β1)-induced EMT in pancreatic cancer cells and tried to ascertain the mechanism related to any observed effects. Human pancreatic cancer cell lines (BxPC-3, PANC-1 and MIAPaCa-2) were stimulated by TGF-β1, and evaluated for morphological changes using immunofluorescence and EMT-related factors (i.e., E-cadherin, Vimentin, Snail or ZEB-1) using RT-PCR. To examine the effect of heat on EMT, the cancer cells were heat-treated at 43°C for 1 h then stimulated with TGF-β1. We then evaluated whether or not heat treatment changed the expression of EMT-related factors and cell migration and also whether Smad activation was inhibited in TGF-β signaling. After being treated with TGF-β1, pancreatic cancer cells resulted in EMT and cell migration was enhanced. Heat treatment inhibited TGF-β1-induced changes in morphology, inhibited the expression of EMT-related factors, and attenuated TGF-β1-induced migration in pancreatic cancer cells. Additionally, we observed that heat treatment blocked TGF-β1-induced phosphorylation of Smad2 in PANC-1 cells. Our results suggest that heat treatment can suppress TGF-β1-induced EMT and opens the possibility of a new therapeutic use of hyperthermia as a potential treatment for cancer metastasis.     

Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients

Context: To develop a personalized peptide vaccine (PPV) for recurrent ovarian cancer patients and evaluate its efficacy from the point of view of overall survival (OS), Phase II study of PPV was performed.

Patients and methods: Forty-two patients, 17 with platinum-sensitive and 25 with platinum-resistant recurrent ovarian cancer, were enrolled in this study and received a maximum of four peptides based on HLA-A types and IgG responses to the peptides in pre-vaccination plasma.

Results: Expression of 13 of the 15 parental tumor-associated antigens encoding the vaccine peptides, with the two prostate-related antigens being the exceptions, was confirmed in the ovarian cancer tissues. No vaccine-related systemic severe adverse events were observed in any patients. Boosting of cytotoxic T lymphocytes or IgG responses specific for the peptides used for vaccination was observed in 18 or 13 of 42 cases at 6th vaccination, and 19 or 29 of 30 cases at 12th vaccination, respectively. The median survival time (MST) values of the platinum-sensitive- and platinum-resistant recurrent cases were 39.3 and 16.2 months, respectively. The MST of PPV monotherapy or PPV in combination with any chemotherapy during the 1st to 12th vaccination of platinum-sensitive cases was 39.3 or 32.2 months, and that of platinum-resistant cases was 16.8 or 16.1 months, respectively. Importantly, lymphocyte frequency and epitope spreading were significantly prognostic of OS.

Discussion and conclusion: Because of the safety and possible prolongation of OS, a clinical trial of PPV without chemotherapy during the 1st to 12th vaccination in recurrent ovarian cancer patients is merited.     

Immunogenicity of the Trivalent Inactivated Influenza Vaccine in Young Children Less than 4 Years of Age,with a Focus on Age and Baseline Antibodies

In this study, we assessed the effects of the prevaccination titer and age on the immunogenicity of a low dose of influenza vaccine in children less than 4 years of age. A total of 259 children received two vaccine doses (0.1 ml for 0-year-olds and 0.2 ml for children 1 year of age or older) 4 weeks apart during the 2005/2006 season. The hemagglutination inhibition antibody titers were measured before vaccination and 4 weeks after the first and second doses. The geometric mean titer, mean fold rise, seroresponse proportion (≥4-fold rise in titer), and seroprotection proportion (titer ≥1:40) were calculated for the prevaccination titer and age categories. A multivariate logistic regression analysis was performed using the seroresponse and seroprotection proportions as dependent variables and the prevaccination titer and age as explanatory variables. As for the seroresponse against the H1 antigen after the first dose, the adjusted odds ratios of the prevaccination titers (versus <1:10) were 2.2 (95% confidence interval, 0.8 to 5.8) at 1:10 to 1:20 and 0.14 (0.04 to 0.49) at ≥1:40. The corresponding figures for ages were 0.03 (0.01 to 0.07) for the 0-year-olds and 0.17 (0.08 to 0.34) for the 1-year-olds compared with the 2- to 3-year-olds (P_trend < 0.001). Similar results were also obtained for the H3 and B strains. Significantly elevated odds ratios for seroprotection were observed with greater prevaccination titers and older ages for all strains. The prevaccination titer and age were independently associated with the antibody response in young children. The immune response was weaker in the younger children and those without preexisting immunity.     

Proliferative glomerulonephritis with monoclonal IgM deposits without Waldenström's macroglobulinemia: case report and review of the literature

A 38-year-old man was presented with nephrotic syndrome associated with hematuria and mild hypocomplementemia. Renal biopsy revealed lobular mesangial proliferation, thickened capillary walls, and intraluminal protein thrombi. Immunofluorescence showed marked and mild depositions of immunoglobulin (Ig) M heavy chains and complement C3, respectively, in a peripheral lobular pattern. On light chain staining, only kappa (κ) light and IgM heavy chains showed a similar pattern. Electron microscopy showed fine granular electrondense deposits in subendothelial areas and numerous globular deposits (varying size and density) in glomerular capillary lumens. Serum levels of Ig κ, but not of free κ, light chains were significantly increased. Bone marrow aspiration revealed a normocellular marrow. Waldenstr?m's macroglobulinemia and cryoglobulinemia were ruled out. Clinically, steroid therapy was ineffective and proteinuria persisted. This report demonstrates that glomerular deposition of monoclonal IgM-κ can produce membranoproliferative- like changes in the glomeruli. This condition may be recognized as proliferative glomerulonephritis with monoclonal IgM deposits similar to the recently recognized proliferative glomerulonephritis with monoclonal IgG deposits.     

Evaluation of Tumor Stiffness by Elastography Is Predictive for Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

Background

Breast elastography (EG), which can objectively evaluate tumor stiffness, has been useful for differentiation of benign and malignant breast lesions. However, the value of EG for prediction of response to systemic therapy is poorly understood.

Methods

The baseline evaluations of EG in 55 patients who received neoadjuvant chemotherapy were reviewed. We investigated the correlation between tumor stiffness and response to neoadjuvant chemotherapy. Tumor stiffness was evaluated by the Tsukuba elasticity scoring system.

Results

The mean EG scores were significant lower for the clinical and pathologic complete response (pCR) groups than for the others. When we categorized patients into two groups according to tumor stiffness, 26 patients were assigned to the low EG group (soft, scores from 1 to 3) and 29 patients were assigned to the high EG group (hard, score 4 and 5). The low EG group had significantly higher clinical complete response and pCR rates than the high EG group (clinical complete response, low EG group 38?% vs. high EG group 10?%, P?=?0.024; pCR, low EG group 50?% vs. high EG group 14?%, P?=?0.003, respectively). Furthermore, multivariate analysis indicated that estrogen receptor, human epidermal growth factor receptor 2, and low EG (odds ratio 13.04, 95?% confidence interval 1.19?C458.28, P?=?0.035) were independent predictive factors of pCR.

Conclusions

Tumor stiffness evaluated by EG bears predictive potential for response to neoadjuvant chemotherapy. Stiffness evaluated by EG may be recognized as a clinically significant tumor characteristic, comparable to other data obtained by functional imaging techniques.     

Racial and Ethnic Disparities in the Continuation of Community-Based Children’s Mental Health Services

This paper examines racial and ethnic disparities in continuation of mental health services for children and youth in California and how English language proficiency moderates the effect of race/ethnicity on the continuation of service. While previous research indicated racial/ethnic or geographic disparities in accessing mental health services among children and youth, few studies specifically focused on the continuation of mental health care. The authors used administrative data from California county mental health services users under age 25. Applying logistic regression, English language proficiency was found to be the major determinant of continuation of mental health services in this age group. With the exception of children of Asian descent, non-English speaking children and youth of diverse racial/ethnic background were significantly less likely to continue receiving mental health services compared with White English-speaking peers, even after controlling for sociodemographic, clinical and county characteristics.     

Effects of intravenous amino acids on anesthesia-induced hypothermia in ovariectomized rats

A decrease in core temperature during general anesthesia is attenuated by infusion of an intravenous amino acid mixture. The purpose of the present study was to investigate the influence of physical and endocrine changes caused by ovariectomy on the inhibitory effect of amino acid infusion on anesthesia-induced hypothermia. Sprague-Dawley female rats were divided into a sham-operated (Sham) group and an ovariectomized (OVX) group. Saline solution or an amino acid mixture solution was infused for 180 min during sevoflurane anesthesia, and the rectal temperature was measured (4 groups). Intraperitoneal white adipose tissue mass, bilateral gastrocnemius weight and plasma insulin levels were measured. In the Sham rats, no inhibitory effect of the amino acid mixture on anesthesia-induced hypothermia was found, while in the OVX rats, hypothermia was significantly decreased. The intraperitoneal fat weight/body weight ratio was significantly higher in the OVX rats than in the Sham rats, but the gastrocnemius weight/body weight ratio was not significantly different. After amino acid infusion, the plasma insulin level was significantly higher in the OVX rats than in the Sham rats. In conclusion, our findings suggest that, in rats, ovarian function or female hormone affects protein turnover mediated by increase in insulin secretion and, thus, decreases the inhibitory effect of an infusion of amino acid mixture on anesthesia-induced hypothermia.