TRP genes family expression in colorectal cancer.

UNLABELLED: Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. MATERIAL AND METHODS: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. RESULTS: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. CONCLUSIONS: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues.

Endocrine therapy alone vs. chemotherapy plus endocrine therapies for the treatment of elderly patients with endocrine-responsive and node positive breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).

PURPOSE: The extra benefit of adding chemotherapy to effective endocrine therapy (ET) has not been clearly or consistently identified in patients older than 70 years with estrogen receptor (ER) positive and node positive breast cancer. The aim of this study was to evaluate the efficacy of adjuvant ET vs. chemotherapy plus endocrine therapies (Chemo/ET) in such patients. METHODS: In this retrospective multicenter study 191 patients ≥ 70 years with operated hormone receptor breast cancer, who were administered adjuvant ET or Chemo/ET were assessed. RESULTS: The median patient follow-up time was 29.0 months (range 1-252). Therefore disease free survival (DFS) and overall survival (OS) analysis was limited, due to the rather short median follow-up, and only 30-month cumulative percentages are reported herein. The 30-month DFS rates were 50.0% in the ET arm and 49.0% in the Chemo/ET arm (p=0.79). The 30-month OS rates were 86% in the ET arm and 96.0% in the Chemo/ET arm (p=0.08). Cox proportional hazard model showed that only surgery was independent prognostic factor for survival (p=0.047), while tumor size showed a strong trend for statistical significance (p=0.051). CONCLUSION: The addition of chemotherapy to endocrine therapy in older patients has no significant impact on DFS and OS.

Sunitinib-induced autoimmune thyroiditis in a patient with metastatic renal cell carcinoma: a case report.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor that was newly approved by the FDA for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. Although generally well tolerated, common side effects of sunitinib have been reported, with an important and well-recognized example being hypothyroidism. Although the exact mechanism of sunitinib-induced hypothyroidism is unclear, some authors have suggested sunitinib might induce hypothyroidism by the blockade of iodine uptake, destructive thyroiditis and inhibition of peroxidase activity. In these studies autoimmune-mediated hypothyroidism could not be demonstrated as an etiological factor. We herein report the case of a 71-year-old woman diagnosed as metastatic renal cell carcinoma with severe autoimmune hypothyroidism associated with sunitinib after 10 months of treatment. To the best of our knowledge, this is the first report that shows sunitinib may induce autoimmune thyroiditis. Further clinical and experimental studies with larger patient groups are required to verify the findings of the present study. Routine monitoring of thyroid autoantibodies including antithyroglobulin and antithyroid peroxidase antibodies and thyroid ultrasonography are recommended during the treatment of sunitinib-induced hypothyroidism.

Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study.

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.