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The pks + E. coli metabolite colibactin caused a unique mutational signature in intestinal organoids. ©2020 American Association for Cancer Research.A new method called MicroMapping can identify nanoscale protein-protein interactions on live cells. ©2020 American Association for Cancer Research.A chemotherapy-induced shift to ICOSL+ B cells in breast tumors correlated with better survival. ©2020 American Association for Cancer Research.A large international study found that the composition of the intestinal microbiome can predict clinical outcomes in patients undergoing allogenic hematopoietic-cell transplant (HCT) for blood cancers. The findings may help assess patients' transplantation-related mortality risk and aid in developing interventions to prevent or mitigate microbiome changes that affect HCT outcomes. ©2020 American Association for Cancer Research.Symmetric division of stem cells positive for gastrin receptor CCK2R is linked to gastric cancer. ©2020 American Association for Cancer Research.INTRODUCTION Pre-malignant cervical disease and invasive cervical cancer present a significant global health burden with respect to morbidity and mortality, mostly in low- and middle-income countries. Human papillomavirus (HPV) infection typically manifests for the first time in adolescence. We aimed to identify adolescent sociodemographic and anthropometric characteristics associated with subsequent risk for pre-malignant cervical disease and cervical cancer, in a country that offers free screening and HPV vaccines. METHODS This historical cohort study included 969 123 Israeli women examined and anthropometrically measured at age 17 years between January 1967 and December 2011. Data on pre-malignant disease and invasive cervical tumors were obtained from the national cancer registry by linkage. We excluded non-Jewish minorities (a total of 25 472 women) and orthodox/ultraorthodox Jewish women since these populations are not required by law to serve in the military, as well as women with a pre-examination diall stature, and education were associated with pre-malignant cervical disease and cervical cancer incidence, while adolescent overweight and obesity were inversely associated with only pre-malignant cervical disease. Despite free screening and HPV vaccines, these findings suggest that there is still a need for appropriate safe sex and screening education in adolescence. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION Molecular classification of endometrial carcinoma has been proposed to predict survival. However, its role in patient management remains to be determined. We aimed to identify whether a molecular and immunohistochemical classification of endometrial carcinoma could improve decision-making for adjuvant therapy. METHODS All consecutive patients treated for endometrial carcinoma between 2010 and 2017 at Cochin University Hospital were included. Clinical risk of relapse was based on European Society for Medical Oncology-European Society of Gynaecological Oncology-European SocieTy for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) consensus. The clinical event of interest was event-free survival. Formalin-fixed paraffin-embedded tissue samples were processed for histopathological analysis and DNA extraction. The nuclear expression of mismatch repair and TP53 proteins was analyzed by immunohistochemistry. Next-generation sequencing of a panel of 15 genes including TP53 and POLE was performed using Ampliseq and independently of clinical risk of relapse (aHR 3.92, 95% CI 1.59 to 9.64). Among patients with FIGO stage I-II tumors, 6 (38%) TP53-mutated tumors had low/intermediate clinical risk of relapse and did not receive adjuvant chemotherapy or radiotherapy. CONCLUSION Endometrial carcinoma molecular classification identified potentially under-treated patients with poor molecular prognosis despite being at low/intermediate clinical risk of relapse. Consideration of molecular classification in adjuvant therapeutic decisions should be evaluated in prospective trials. © IGCS and ESGO 2020. https://www.selleckchem.com/products/2-nbdg.html No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. CASE PRESENTATION A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1. CONCLUSION This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.PURPOSE Patients with cancer receiving tumor-reactive humanized monoclonal antibody (mAb) therapy can develop a human antihuman antibody (HAHA) response against the therapeutic mAb. We evaluated for HAHA in patients with neuroblastoma treated in a phase I study of humanized anti-GD2 mAb (immunoglobulin (Ig)G1 isotype), hu14.18K322A (NCT00743496). The pretreatment sera (collected prior to mAb treatment) from 9 of 38 patients contained antitherapeutic antibodies, even though they had no prior mAb exposure. We sought to characterize these pre-existing antitherapeutic antibodies (PATA). EXPERIMENTAL DESIGN The PATA+ pretreatment samples were characterized via ELISA; clinical associations with PATA status were evaluated. RESULTS Pretreatment sera from eight of nine PATA+ patients also bound rituximab and demonstrated preferential ELISA reactivity against the Fc portions of hu14.18K322A and rituximab as compared with the Fab portions of these mAbs. These PATA+ sera also recognized dinutuximab (human IgG1 isotype) and mouse IgG2a isotype mAbs, but not a mouse IgG1 isotype or the fully human panitumumab (IgG2 isotype) mAb.
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