Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer

In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging “cancer methylome”. In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-β (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC

Laparoscopic cholecystectomy for acute calculous cholecystitis : a retrospective study assessing risk factors for conversion and complications

Background: The purpose of the study was to identify risk factors for conversion of laparoscopic cholecystectomy and risk factors for postoperative complications in acute calculous cholecystitis. The most common complications arising from cholecystectomy were also to be identified. Methods: A total of 499 consecutive patients, who had undergone emergent cholecystectomy with diagnosis of cholecystitis in Meilahti Hospital in 2013-2014, were identified from the hospital database. Of the identified patients, 400 had acute calculous cholecystitis of which 27 patients with surgery initiated as open cholecystectomy were excluded, resulting in 373 patients for the final analysis. The Clavien-Dindo classification of surgical complications was used. Results: Laparoscopic cholecystectomy was initiated in 373 patients of which 84 (22.5%) were converted to open surgery. Multivariate logistic regression identified C-reactive protein (CRP) over 150 mg/l, age over 65 years, diabetes, gangrene of the gallbladder and an abscess as risk factors for conversion. Complications were experienced by 67 (18.0%) patients. Multivariate logistic regression identified age over 65 years, male gender, impaired renal function and conversion as risk factors for complications. Conclusions: Advanced cholecystitis with high CRP, gangrene or an abscess increase the risk of conversion. The risk of postoperative complications is higher after conversion. Early identification and treatment of acute calculous cholecystitis might reduce the number of patients with advanced cholecystitis and thus improve outcomes.Peer reviewe

The Y3?xBa3+xCu6O14+? system of superconductors

Members of the Y3?xBa3+xCu6O14+? system prepared at relatively low temperatures by nitrate decomposition have a tetragonal structure and show superconducting transitions (zero-resistance) around 50K

High-temperature superconductivity in bismuth-copper oxides of the type BimMnCupOx (M=Mg, Ca, Sr, Ba, Bi)

Several oxides of the Bi m M n Cu p O x family (m=2, 3;n=2, 3, 4;p=1, 2, 3 and M=alkaline earth or Bi), possessing structures similar to the Aurivillius family of oxides, show highT c superconductivity

Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review

Jin Seok Ahn,1 Johnson Lin,2 Setsuro Ogawa,3 Chen Yuan,4 Tony O’Brien,5,6 Brian HC Le,7 Andrea M Bothwell,8 Hanlim Moon,9 Yacine Hadjiat,9 Abhijith Ganapathi9 1Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea; 2Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China; 3Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan; 4Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Marymount University Hospital and Hospice, 6Cork University Hospital, College of Medicine and Health, University College Cork, Cork, Ireland; 7Department of Palliative Care, Royal Melbourne Hospital, Parkville, VIC, Australia; 8In Vivo Communications (Asia), 9Mundipharma Pte Ltd, Singapore, Singapore Abstract: Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion.Keywords: analgesia, cancer pain management, chronic pain/drug therapy, drug evaluation, pain management, patch analgesic

Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion