Ethnic Differences in Susceptibility to the Effects of Platinum- Based Chemotherapy

There is substantial interindividual variability in the efficacy and tolerability of anticancer drugs. Such differences can be greater between individuals of different ethnicities. The clinical studies demonstrate that individuals from Asia (East Asia) are more susceptible to the effects of platinum-containing chemotherapies than their Western counterparts. To determine whether population-related genomics (i.e., frequencies of DNA polymorphisms) contribute to differences in patient outcomes, polymorphisms in 109 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle, and apoptosis were tested in Russian (Caucasians) and Yakut (North Asians) ovarian cancer patients receiving cisplatin-based chemotherapy. Totally, 232 polymorphisms were genotyped in individual DNA samples using conventional PCR and arrayed primer extension technology. Single nucleotide polymorphisms (SNPs) in more than 30 genes were found to be associated with one or more of clinical end points (i.e., tumor response, progression-free survival, overall survival, and side effects). However, all associations between SNPs and clinical outcomes were specific for each of ethnic group studied. These findings let us to propose the existence of distinctive ethnic-related characteristics in molecular mechanisms determining the sensitivity of patients to platinum drug effects

Transcriptomic and Genomic Testing to Guide Individualized Treatment in Chemoresistant Gastric Cancer Case

Gastric cancer is globally the fifth leading cause of cancer death. We present a case report describing the unique genomic characteristics of an Epstein–Barr virus-negative gastric cancer with esophageal invasion and regional lymph node metastasis. Genomic tests were performed first with the stomach biopsy using platforms FoundationOne, OncoDNA, and Oncopanel at Dana Farber Institute. Following neoadjuvant chemotherapy, residual tumor was resected and the stomach and esophageal residual tumor samples were compared with the initial biopsy by whole exome sequencing and molecular pathway analysis platform Oncobox. Copy number variation profiling perfectly matched the whole exome sequencing results. A moderate agreement was seen between the diagnostic platforms in finding mutations in the initial biopsy. Final data indicate somatic activating mutation Q546K in PIK3CA gene, somatic frameshifts in PIH1D1 and FBXW7 genes, stop-gain in TP53BP1, and a few somatic mutations of unknown significance. RNA sequencing analysis revealed upregulated expressions of MMP7, MMP9, BIRC5, and PD-L1 genes and strongly differential regulation of several molecular pathways linked with the mutations identified. According to test results, the patient received immunotherapy with anti-PD1 therapy and is now free of disease for 2 years. Our data suggest that matched tumor and normal tissue analyses have a considerable advantage over tumor biopsy-only genomic tests in stomach cancer

A Comprehensive Northern Hemisphere Particle Microphysics Data Set From the Precipitation Imaging Package

Abstract Microphysical observations of precipitating particles are critical data sources for numerical weather prediction models and remote sensing retrieval algorithms. However, obtaining coherent data sets of particle microphysics is challenging as they are often unindexed, distributed across disparate institutions, and have not undergone a uniform quality control process. This work introduces a unified, comprehensive Northern Hemisphere particle microphysical data set from the National Aeronautics and Space Administration precipitation imaging package (PIP), accessible in a standardized data format and stored in a centralized, public repository. Data is collected from 10 measurement sites spanning 34° latitude (37°N–71°N) over 10 years (2014–2023), which comprise a set of 1,070,000 precipitating minutes. The provided data set includes measurements of a suite of microphysical attributes for both rain and snow, including distributions of particle size, vertical velocity, and effective density, along with higher‐order products including an approximation of volume‐weighted equivalent particle densities, liquid equivalent snowfall, and rainfall rate estimates. The data underwent a rigorous standardization and quality assurance process to filter out erroneous observations to produce a self‐describing, scalable, and achievable data set. Case study analyses demonstrate the capabilities of the data set in identifying physical processes like precipitation phase‐changes at high temporal resolution. Bulk precipitation characteristics from a multi‐site intercomparison also highlight distinct microphysical properties unique to each location. This curated PIP data set is a robust database of high‐quality particle microphysical observations for constraining future precipitation retrieval algorithms, and offers new insights toward better understanding regional and seasonal differences in bulk precipitation characteristics

Measurement of the charge asymmetry in top quark pair production in pp collisions at √s = 7 using the ATLAS detector

A measurement of the top-antitop production charge asymmetry A is presented using data corresponding to an integrated luminosity of 1.04 fb −1 of pp collisions at TeV collected by the ATLAS detector at the LHC. Events are selected with a single lepton (electron or muon), missing transverse momentum and at least four jets of which at least one jet is identified as coming from a b -quark. A kinematic fit is used to reconstruct the event topology. After background subtraction, a Bayesian unfolding procedure is performed to correct for acceptance and detector effects. The measured value of A is , consistent with the prediction from the Monte Carlo generator of A =0.006±0.002. Measurements of A in two ranges of invariant mass of the top-antitop pair are also shown