5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC.

PURPOSE: Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. METHODS: Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2-3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. RESULTS: There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. CONCLUSIONS: Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC

Purpose Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. Methods Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2­3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. Results There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. Conclusions Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.

Oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma.

AIMS: In adult population, the renal cell carcinoma (RCC) is one of the most common urological malignancies. It is meaningful to research for the molecular markers which are involved in the occurrence and development of RCC. Therefore, we concentrate on illuminating the role of microRNA-154-5p in progression of RCC and explore its prognostic values. MAIN METHODS: The real-time quantitative polymerase chain reaction (RT-qPCR) was applied to determine expression level of miR-154-5p in tissues. Afterwards, the transfected cell lines ACHN and 786-O were used for the CCK-8 assay, MTT assay, wound healing assay, transwell assay and flow cytometric assay to explore the role of miR-154-5p in regulating cellular function. In addition, formalin-fixed paraffin-embedded (FFPE) renal cancer samples were used for detecting the relationship between expression level of miR-154-5p and clinical information. Furthermore, univariate and multivariate Cox proportional-hazards regression analyses, and the Kaplan-Meier survival curves were performed to evaluate the prognostic value of miR-154-5p in RCC. KEY FINDINGS: The RT-qPCR indicated that miR-154-5p is up-regulated in RCC pathologic specimens and cell lines. Results of study also demonstrated that upregulation of miR-154-5p reduced cell apoptosis and promoted cell proliferation, viability, migration as well as invasion in RCC cells. The prognosis analyses indicated that the expression level of miR-154-5p is associated with the prognosis of renal cancer, and the overall survival of patients with low expression is longer. SIGNIFICANCE: The present study revealed that the oncogene miR-154-5p regulates cellular function and acts as a molecular marker with poor prognosis in renal cell carcinoma.

Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis.

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects.

Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects. .

Gamma knife surgery for pineal region tumors: an alternative strategy for negative pathology.

OBJECTIVE: Pineal region tumors (PRTs) are uncommon, and treatments vary among neoplasm types. The authors report their experience with gamma knife surgery (GKS) as an initial treatment in a series of PRT patients with unclear pathological diagnoses. METHOD: Seventeen PRT patients with negative pathology who underwent GKS were retrospectively studied. Nine patients had further whole-brain and spinal cord radiotherapy and chemotherapy 6-9 months after GKS. RESULTS: Sixteen of 17 cases were followed up over a mean of 33.3 months. The total response rate was 75%, and the control rate was 81.3%. No obvious neurological deficits or complications were attributable to GKS. CONCLUSION: The findings indicate that GKS may be an alternative strategy in selected PRT patients who have negative pathological diagnoses, and that good outcomes and quality of life can be obtained with few complications.

Gamma knife surgery for pineal region tumors: an alternative strategy for negative pathology / Cirurgia com gamma knife como tratamento experimental para tumores da região da pineal: uma estratégia alternativa quando os dados anatomopatológicos são negativos

Objective : Pineal region tumors (PRTs) are uncommon, and treatments vary among neoplasm types. The authors report their experience with gamma knife surgery (GKS) as an initial treatment in a series of PRT patients with unclear pathological diagnoses. Method : Seventeen PRT patients with negative pathology who underwent GKS were retrospectively studied. Nine patients had further whole-brain and spinal cord radiotherapy and chemotherapy 6–9 months after GKS. Results : Sixteen of 17 cases were followed up over a mean of 33.3 months. The total response rate was 75%, and the control rate was 81.3%. No obvious neurological deficits or complications were attributable to GKS. Conclusion : The findings indicate that GKS may be an alternative strategy in selected PRT patients who have negative pathological diagnoses, and that good outcomes and quality of life can be obtained with few complications. .

Tumores da região da pineal (TRP) são pouco frequentes e as propostas de tratamento são bastante variadas. Os autores relatam sua experiência em cirurgias com uso gamma knife (CGK) como tratamento experimental inicial em séries de TRP que não têm diagnóstico anatomopatológico ou nos quais o diagnóstico não ficou claro. Foram estudados retrospectivamente 17 pacientes com TRP nestas condições e que foram submetidos a CGK. Destes, 9 pacientes foram submetidos posteriormente a radioterapia de todo o encéfalo e medula espinhal entre 6 e 9 meses depois da CGK. Dezesseis dos 17 pacientes foram acompanhados por um período médio de 33,3 meses. A taxa total de resposta nos pacientes foi de 75% e a taxa dos controles, 81,3%. Não houve nenhum déficit neurológico evidente que pudesse ser atribuído à CGK. A CGK como tratamento experimental pode ser uma estratégia alternativa no grupo específico de pacientes com TRP em que não há diagnóstico anatomopatológico, podendo ser obtida uma boa qualidade de vida com poucas complicações para esse grupo de pacientes.

Helicobacter pylori infection of the larynx may be an emerging risk factor for laryngeal squamous cell carcinoma.

INTRODUCTION: Several studies have implicated Helicobacter pylori as a risk factor in laryngeal cancer, but other studies disagree. It is fundamental that the relationship between Helicobacter pylori and laryngeal cancer be verified in order to provide evidence of ways to prevent the initiation and development of this carcinoma. MATERIALS AND METHODS: In total, 81 patients with laryngeal squamous cell carcinoma and 75 control subjects were enrolled in a case-control study. Semi-nested polymerase chain reaction techniques were applied to detect Helicobacter pylori in the laryngeal mucosa and enzyme-linked immunosorbent assays were used to detect serum antibodies against Helicobacter pylori. Risk factors associated with laryngeal carcinoma were analyzed using logistic regression models. RESULTS: The presence of Helicobacter pylori in the larynx was higher in patients with laryngeal cancer than in control subjects (71.6 vs. 25.3 %, p < 0.001). Among patients with laryngeal carcinoma, rates of Helicobacter pylori infection were higher in normal laryngeal tissues than in tumor tissues. After adjusting for confounding factors, regression analysis indicated that the microbe was an independent risk factor for laryngeal cancer (OR = 7.15, 95 % CI [3.29, 15.53], p < 0.001). CONCLUSIONS: This study suggests that Helicobacter pylori is present in the mucosa of the larynx. The microorganism may be an independent risk factor for laryngeal squamous cell carcinoma. The laryngeal mucosa thus provides a reservoir for the bacteria possibly, and is a likely staging place for its transmission to other areas.