Notes

mTOR Knockdown inside the Infralimbic Cortex Calls forth A Depressive-like Express in Mouse button.
Objective To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC). Background The current treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients. Methods Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model. Results Patients who received 60-75 Gy/30-35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37-0.78, P = 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46-0.84, P = 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67-0.95, P = 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10-0.75, P = 0.007), PFS (HR, 0.60, 95% CI, 0.42-0.87, P = 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29-1.03, P = 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS. Conclusions Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor. Copyright © 2020 Li, Jia, Sun, Guo, Liu, Liu, Yan, Luo, Sun, Guo, Mo, Tang, Chen and Mai.Background A Phase III randomized controlled trial investigating the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for locally advanced cervical cancer patients is being conducted in South Africa (Human Research Ethics Committee approval M1704133; ClincialTrials.gov ID NCT03332069). Two hundred and ten participants were randomized and 202 participants were eligible for six month local disease control evaluation. Screening 18F-FDG PET/CT scans were conducted and repeated at six months post-treatment. Significant improvement in local control was reported in the mEHT group and complete metabolic resolution (CMR) of extra-pelvic disease was noted in some participants. We report on an analysis of the participants with CMR of disease inside and outside the radiation field. Method Participants were included in this analysis if nodes outside the treatment field (FDG-uptake SUV>2.5) were visualized on pre-treatment scans and if participants were evaluated by 18F-FDG PET/CT scans at six months post-treatment. Results One hundred and eight participants (mEHT HIV-positive n = 25, HIV-negative n = 29; Control Group HIV-positive n = 26, HIV-negative n = 28) were eligible for analysis. There was a higher CMR of all disease inside and outside the radiation field in the mEHT Group n = 13 [24.1%] than the control group n = 3 [5.6%] (Chi squared, Fisher's exact p = 0.013) with no significant difference in the extra-pelvic response to treatment between the HIV-positive and -negative participants of each group. Conclusion The CMR of disease outside the radiation field at six months post-treatment provides evidence of an abscopal effect which was significantly associated with the addition of mEHT to treatment protocols. This finding is important as the combined synergistic use of radiotherapy with mEHT could broaden the scope of radiotherapy to include systemic disease. Copyright © 2020 Minnaar, Kotzen, Ayeni, Vangu and Baeyens.Background We report functional and clinical data uncovering the significance of B-cell lymphoma/leukemia 11A (BCL11A) in laryngeal squamous cell carcinoma (LSCC). Methods We examined BCL11A expression in a cohort of LSCC patients and evaluated the association between BCL11A expression and clinicopathological features. We investigated the consequences of overexpressing BCL11A in the LSCC cell line on proliferation, migration, invasion, cell cycle, chemosensitivity, and growth in vivo. We explored the relationship between BCL11A and MDM2 in LSCC and tumorigenesis pathways by using the Human Cancer PathwayFinder Array. Results High levels of BCL11A were found in LSCC tissues and were more frequently associated with advanced lymphatic metastasis stages with poor prognoses. BCL11A overexpression enhanced LSCC proliferation in vitro and vivo. A positive correlation between MDM2 and BCL11A expression was identified. Conclusions These data uncover important functions of BCL11A in LSCC and identify BCL11A as a prognostic biomarker and potential therapeutic target in LSCC. Copyright © 2020 Zhou, Zhou, Zhang, Tang, Tang, Shi, Yang, Zhou, Liu, Yu, Liu, Tao and Lu.Background As the sixth most common cancer of worldwide, head and neck cancers (HNC) are springing from oral cavity, pharynx and larynx and there is no strong biomarker for prognosis. Rates of 5 years survival with HNC remain relatively low in decades with improvement of treatments. Evidence that single nucleotide polymorphisms (SNPs) play a part in cancer prognosis is growing. Methods We conducted an exome-wide association study among 261 patients with head and neck squamous cell carcinoma (HNSCC) and then validated in The Cancer Genome Atlas (TCGA) database for survival by using the Cox proportional hazards regression models and Kaplan-Meier analyses. Results After combining the result of the two stages, 4 SNPs were significantly associated with HNSCC survival (rs16879870 at 6q14.3 adjusted HR = 2.02, 95%CI = 1.50-2.73, P = 3.88 × 10-6; rs2641256 at 17p13.2 adjusted HR = 0.67, 95%CI = 0.56-0.80, P = 7.51 × 10-6; rs2761591 at 11p13 adjusted HR = 2.07, 95%CI = 1.50-2.87, P = 1.16 × 10-5; and rs854936 at 22q11.21 adjusted HR = 1.92, 95%CI = 1.43-2.57, P = 1.27 × 10-5). Besides, we constructed a receiver operating characteristic (ROC) model to estimate predictive effect of the novel SNPs combined with clinical stage in HNSCC prognosis (AUC = 0.715). We also found the genotype of rs16879870 and rs854936 was significantly associated with the expression of gene GJB7 (P = 0.013) and RTN4R (P = 0.047) in cancer tissues of TCGA, respectively. Conclusion Our findings suggested that the SNPs (rs16879870, rs2641256, rs2761591, rs854936) might play a crucial role in prognosis of HNSCC. Copyright © 2020 He, Ji, Li, Wang, Ma and Yuan.Objectives To predict the anaplastic lymphoma kinase (ALK) mutations in lung adenocarcinoma patients non-invasively with machine learning models that combine clinical, conventional CT and radiomic features. Methods This retrospective study included 335 lung adenocarcinoma patients who were randomly divided into a primary cohort (268 patients; 90 ALK-rearranged; and 178 ALK wild-type) and a test cohort (67 patients; 22 ALK-rearranged; and 45 ALK wild-type). One thousand two hundred and eighteen quantitative radiomic features were extracted from the semi-automatically delineated volume of interest (VOI) of the entire tumor using both the original and the pre-processed non-enhanced CT images. Twelve conventional CT features and seven clinical features were also collected. Normalized features were selected using a sequential of the F-test-based method, the density-based spatial clustering of applications with noise (DBSCAN) method, and the recursive feature elimination (RFE) method. Selected features were then usr study demonstrates that radiomics-derived machine learning models can potentially serve as a non-invasive tool to identify ALK mutation of lung adenocarcinoma. Copyright © 2020 Song, Zhu, Mao, Li, Han, Du, Wu, Song and Jin.[This corrects the article DOI 10.3389/fonc.2019.01430.]. Copyright © 2020 Lemos, Oliveira, Martins, de Azevedo, Rodrigues, Ketzer and Rumjanek.Background Although international guidelines recommend bone screening for premenopausal breast cancer patients taking adjuvant tamoxifen, the effects of tamoxifen on osteoporosis and related risks remain controversial. The objective of this study was to investigate the incidence of and risk factors for osteoporosis and osteoporotic fractures in younger breast cancer patients. Methods A nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. The rates of osteoporosis and osteoporotic fracture were calculated as incident cases per person-year and disease-free probability rates were analyzed with the Kaplan-Meier method. To identify risk factors for osteoporosis and osteoporotic fracture, a multivariable Cox proportional hazard regression model was applied. Results From January 2009 to December 2014, a total of 47,649 breast cancer patients were included. The incidence rates of osteoporosis and osteoporotic fracture were 23.59 and 2.40 peryright © 2020 Lee, Alqudaihi, Kang, Kim, Lee, Ko, Son, Ahn, Lee, Han, Kim, Hur, Lee and Chung.Background To assess the role of nodal involvement in stage III renal cell carcinoma (RCC) according to the American Joint Committee on Cancer (AJCC) 8th staging system. We compared the survival outcomes of RCC patients with pT1-3N1M0 disease and those with pT3N0M0 or stage IV (stratified as pT4NanyM0 and pTanyNanyM1) disease in a large population-based cohort. Methods A cohort of 3,112 eligible patients with RCC was identified from the Surveillance, Epidemiology, and End Results (SEER) database, registered between January 2004 and December 2015. Kaplan-Meier and Cox proportional hazards models were used to evaluate the overall survival (OS), and cancer-specific survival (CSS). The prognostic value of the modified stage for pT1-3N1M0 disease was assessed by nomogram-based analyses. Propensity score matching (PSM) was used to adjust for potential baseline confounding. Results Patients with pT1-3N1M0 disease showed similar survival outcomes (median OS 41.0 vs. 38.0 months, P = 0.77; CSS 45.0 vs. 39.0 months, P = 0.59) to pT4NanyM0 patients, whereas the significantly better survival outcome was found for pT3N0M0 patients. After PSM, comparable survival rates were observed between pT1-3N1M0 group and pT4NanyM0 group, which were still significantly worse than the survival of pT3N0M0 patients. The modified stage IIIA (pT3N0M0), IIIB (pT1-3N1M0, pT4NanyM0), and IV (pTanyNanyM1) showed higher predictive accuracy than AJCC stage system in the nomogram-based analyses (concordance index 0.70 vs. 0.68, P less then 0.001 for OS; 0.71 vs. 0.69, P less then 0.001 for CSS). Conclusions The pT1-3N1M0 RCC might be reclassified as stage IIIB together with pT4NanyM0 disease for better prediction of prognosis, further examination and validation are warranted. Copyright © 2020 Han, Li, Li, Wang, Zhang, Qiao, Song and Fu.Quality assured pathology services are integral to provision of optimal management for patients with head and neck cancer. Pathology services vary globally and are dependent on resources in terms of both laboratory provision and availability of a highly trained and accredited workforce. Ensuring a high-quality pathology service depends largely on close working and effective communication between the clinical team providing treatment and the pathologists providing laboratory input. Laboratory services should be quality assured by achieving external accreditation, most often by conforming to International Organization for Standardization (ISO) standards such as ISO15189 sometimes with ISO17025 or alternatively ISO17020. Quality of diagnostic reporting can be assured by the ISO but clinical teams should endeavor to work with pathologists who engage in continuing professional development, external quality assurance and audit. Research also contributes to diagnostic reporting quality. A number of initiatives in the UK such as the EPSRC/MRC funded Molecular Pathology Nodes and the National Cancer Research Institute Cellular-Molecular Pathology initiative (C-M Path), for example, have linked pathologists, industry and researchers.
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