- MiR-634 sensitizes glioma cells to temozolomide by targeting CYR61 through Raf-ERK signaling pathway. [Journal Article]
- CMCancer Med 2018 Feb 23
- Glioma is the most common intracranial malignant tumors, accounting for about 40% of intracranial tumors. Primary or secondary drug resistance is one of the main reasons for the failure of treatment....
Glioma is the most common intracranial malignant tumors, accounting for about 40% of intracranial tumors. Primary or secondary drug resistance is one of the main reasons for the failure of treatment. The oncogenic or tumor-suppressive roles of miR-634 have been revealed in different types of cancer. However, the role of miR-634 in glioma remains unknown and whether miR-634 could sensitize glioma cells to temozolomide also is unclear. Here, we aim to investigate the biological function of miR-634 and the possible mechanisms in glioma. In this study, we found that miR-634 was downregulated in glioma tissues compared with normal brain tissues, and its expression was associated with tumor size and WHO grade. Importantly, glioma patients with low miR-634 expression showed a shorter survival time than patients which had high expression of miR-634. This study also showed that miR-634 was decreased in temozolomide-resistant glioma cells, and restoration of miR-634 could sensitize the resistant cells to temozolomide by targeting CYR61 through Raf-ERK signaling. Our study provides a potential target for overcome drug resistance in glioma.
- Post-imaging colorectal cancer or interval cancer rates after CT colonography: a systematic review and meta-analysis. [Journal Article]
- LGLancet Gastroenterol Hepatol 2018 Feb 19
- CONCLUSIONS: CT colonography does not lead to an excess of post-test cancers relative to colonoscopy within 3-5 years, and the low 5-year post-imaging colorectal cancer rate confirms that the recommended screening interval of 5 years is safe. Since most post-imaging colorectal cancers arise from perceptual errors, radiologist training and quality assurance could help to reduce post-imaging colorectal cancer rates.
- Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data. [Journal Article]
- JCJ Clin Oncol 2018 Feb 22; :JCO2017748301
- Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by perfor...
Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. Results Data from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P < .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P < .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); > 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS ( P = .043), but not for the DDFS and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.
- Association Between Utilization of Chiropractic Services for Treatment of Low-Back Pain and Use of Prescription Opioids. [Journal Article]
- JAJ Altern Complement Med 2018 Feb 22
- CONCLUSIONS: Among New Hampshire adults with office visits for noncancer low-back pain, the likelihood of filling a prescription for an opioid analgesic was significantly lower for recipients of services delivered by doctors of chiropractic compared with nonrecipients. The underlying cause of this correlation remains unknown, indicating the need for further investigation.
- Dose-escalation is needed for gross disease in high-risk neuroblastoma. [Journal Article]
- PBPediatr Blood Cancer 2018 Feb 22
- CONCLUSIONS: After subtotal resection, patients who received less than 30 Gy had poor local control. Doses of 30-36 Gy are likely needed for optimal control of gross residual disease at the time of consolidative RT in high-risk neuroblastoma.
- E4BP4/NFIL3 modulates the epigenetically repressed Ras effector RASSF8 function through histone methyl transferases. [Journal Article]
- JBJ Biol Chem 2018 Feb 21
- Ras proteins are major human oncogenes and most of the studies are focussed on enzymatic RAS effectors. Recently, non-enzymatic Ras effectors (RASSF-Ras association domain family) have garnered speci...
Ras proteins are major human oncogenes and most of the studies are focussed on enzymatic RAS effectors. Recently, non-enzymatic Ras effectors (RASSF-Ras association domain family) have garnered special attention because of their tumor suppressive properties in contrast to the oncogenic potential of the classical enzymatic Ras effectors. While most members of RASSF family are deregulated by promoter hypermethylation, RASSF8 promoter remains unmethylated in many cancers but the mechanism(s) of its downregulation remains unknown. Here, we unveil E4BP4 as a critical transcriptional modulator repressing RASSF8 expression through histone methyl transferases, G9a and SUV39H1. In line with these observations, we noticed a negative correlation of RASSF8 and E4BP4 expression in primary breast tumor samples. In addition, our data provide evidence that E4BP4 attenuates RASSF8 mediated anti-proliferation and apoptosis shedding mechanistic insights into RASSF8 downregulation in breast cancers. Collectively, our study provides a better understanding on the epigenetic regulation of RASSF8 function and implicate the development of better treatment strategies.
- Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer. [Journal Article]
- NNeoplasia 2018 Feb 18; 20(3):280-288
- CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.
- HMGB2 is associated with malignancy and regulates Warburg effect by targeting LDHB and FBP1 in breast cancer. [Journal Article]
- CCCell Commun Signal 2018 Feb 20; 16(1):8
- CONCLUSIONS: These results disclose a novel role for HMGB2 in reprogramming the metabolic process in breast cancer cells by targeting LDHB and FBP1 and provide potential prognostic predictors for breast cancer patients.
- Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells. [Journal Article]
- TJTohoku J Exp Med 2018; 244(2):133-144
- Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients ...
Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling. Importantly, ASC expression is decreased in lung cancer and various cancers, but its precise function in tumor progression remains unknown. To explore the hitherto unknown role of ASC in lung cancer, we initially searched for lung cancer cell lines with higher expression levels of ASC using Cancer Cell Line Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus established, showed the increased activities of proliferation, motility, and invasion, compared with control cells. Importantly, ASC-knockdown cells also became resistant to cisplatin, but not to other anti-cancer agents, 5-fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC-knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC-knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus, ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc. Targeting Bcl-2 and Src in ASC-downregulated populations of lung cancer may improve treatment outcome.
New Search Next
- The effect of anaesthetic technique during primary breast cancer surgery on neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and return to intended oncological therapy. [Journal Article]
- AAnaesthesia 2018 Feb 19
- Inflammation and immunosuppression contribute to the pathogenesis of cancer. An increased neutrophil-lymphocyte ratio reflects these processes and is associated with adverse cancer outcomes. Whether ...
Inflammation and immunosuppression contribute to the pathogenesis of cancer. An increased neutrophil-lymphocyte ratio reflects these processes and is associated with adverse cancer outcomes. Whether anaesthetic technique for breast cancer surgery influences these factors, and potentially cancer recurrence, remains unknown. We conducted a secondary analysis in patients enrolled in an ongoing trial of anaesthetic technique on breast cancer recurrence. The primary hypothesis was that postoperative neutrophil-lymphocyte ratio is lower in patients allocated to receive propofol-paravertebral rather than inhalational agent-opioid anaesthesia for primary breast cancer surgery. Among 397 patients, 116 had differential white cell counts performed pre-operatively and postoperatively. Pre-operative neutrophil-lymphocyte ratio was similar in the propofol-paravertebral 2.3 (95%CI 1.8-2.8) and inhalational agent-opioid anaesthesia 2.2 (1.9-3.2) groups, p = 0.72. Postoperative neutrophil-lymphocyte ratio was lower (3.0 (2.4-4.2) vs. 4.0 (2.9-5.4), p = 0.001) in the propofol-paravertebral group. Propofol-paravertebral anaesthesia attenuated the postoperative increase in the neutrophil-lymphocyte ratio.