Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

Pattern Recognition Receptors and Inflammation

At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Conclusions Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann–La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.)

/pdf/improved-survival-with-vemurafenib-in-melanoma-with-braf-4rigjjinh0.pdf

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

mTOR Signaling in Growth Control and Disease

Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org
 .

/pdf/gsva-gene-set-variation-analysis-for-microarray-and-rna-seq-1bwfkmry7e.pdf

GSVA: gene set variation analysis for microarray and RNA-seq data.

PURPOSE Screening for second primary cancer (SPC) is one of the key components to survivorship care. We aim to evaluate the oncologists' experience with SPCs and assess the current practice, perceived barriers, and recommendations related to SPC screening. MATERIALS AND METHODS A nationwide survey was conducted with a representative sample of 496 Korean oncologists. A questionnaire based on the findings from our previous qualitative study was administered. RESULTS More than three-fourths of oncologists (76.3%), who participated in the study, had experience with SPC patients. Over half of them (51.9%) stated that it was an embarrassing experience. While the current management practice for SPC varies, most oncologists (80.2%) agreed on the necessity in proactively providing information on SPC screening. A short consultation time (52.3%), lack of guidelines and evidence on SPC screening (47.7%), and patients' lack of knowledge about SPCs (45.1%) or SPC screening (41.4%) were most frequently reported as barriers to providing appropriate care for managing SPC. Oncologists recommended the development of specific screening programs or guidelines in accordance to the type of primary cancer (65.9%), the development of an internal system for SPC screening within the hospital (59.7%) or systematic connection with the national cancer screening program (44.3%), and education of oncologists (41.4%) as well as patients (48.9%) regarding SPC screening. CONCLUSION Many oncologists reported the occurrence of SPC as an embarrassing experience. Given the variations in current practice and the lack of consensus, further studies are warranted to develop the optimal clinical strategy to provide SPC screening for cancer survivors.

/pdf/oncologists-experience-with-patients-with-second-primary-szy1vngqkq.pdf

Oncologists' Experience with Patients with Second Primary Cancer and the Attitudes toward Second Primary Cancer Screening: A Nationwide Survey.

Admixture has profoundly influenced evolution across the tree of life, including in humans and other primates1,2. However, we have limited insight into the genetic and phenotypic consequences of admixture in primates, especially during its key early stages. Here, we address this gap by combining 50 years of field observations with population and functional genomic data from yellow (Papio cynocephalus) and anubis (P. anubis) baboons in Kenya, in a longitudinally studied population that has experienced both historical and recent admixture3. We use whole-genome sequencing to characterize the extent of the hybrid zone, estimate local ancestry for 442 known individuals, and predict the landscape of introgression across the genome. Despite no major fitness costs to hybrids, we identify signatures of selection against introgression that are strikingly similar to those described for archaic hominins4–6. These signatures are strongest near loci with large ancestry effects on gene expression, supporting the importance of gene regulation in primate evolution and the idea that selection targeted large regulatory effects following archaic hominin admixture7,8. Our results show that genomic data and field observations of hybrids are important and mutually informative. They therefore demonstrate the value of other primates as living models for phenomena that we cannot observe in our own lineage.

https://www.biorxiv.org/content/biorxiv/early/2021/08/19/2021.08.19.456711.full.pdf

Selection against admixture and gene regulatory divergence in a long-term primate field study

Correction to: Oncogene (2004) 23, 3863–3871. doi:10.1038/sj.onc.1207492 Published online 8 December 2003 Since publication of the above manuscript, the authors have identified an omission from the ‘Acknowledgement’ section. The following sentence should have been inserted at the end of this section: ‘This work was supported by the Irving Hansen Memorial Foundation.

/pdf/erratum-multiple-cell-type-specific-elements-regulate-myc-164qcche16.pdf

Erratum: Multiple cell-type-specific elements regulate Myc protein stability

Experimental Techniques in Fluorous Synthesis : A users guide

Overnight fasting before elective surgery has been the routine to reduce the risk of pulmonary aspiration. Recently, several international guidelines for preoperative fasting recommend to intake carbohydrate-containing fluids up to 2 to 3 hours before the induction of anesthesia to improve postoperative recovery. Based on the recommendations, we developed a "preoperative carbohydrate diet" provided for the preoperative patients. The purpose of this case report is to share our experience of applying preoperative carbohydrate loading prior to surgery.

/pdf/preoperative-oral-carbohydrate-loading-in-46oqjxnpye.pdf

So Young Kim

Papers

Oncologists' Experience with Patients with Second Primary Cancer and the Attitudes toward Second Primary Cancer Screening: A Nationwide Survey.

Selection against admixture and gene regulatory divergence in a long-term primate field study

Erratum: Multiple cell-type-specific elements regulate Myc protein stability

Experimental Techniques in Fluorous Synthesis : A users guide

Preoperative Oral Carbohydrate Loading in Pancreaticoduodenectomy