tbuckley/cabot-search huggingface dataset:
Abstract 1964: The mutational pattern of cell cycle checkpoints and regulators in Egyptian colorectal cancer patients
Authors: Amira Salah El-Din Youssef, Mai M. Lotfy, Auhood Nassar, Abdel-Rahman N. Zekri
Journal: Cancer Research (2021)

Abstract Background: Uncontrolled proliferation is a hallmark of cancer cells. Many cell cycle checkpoints and regulators are altered in tumors which in turn results in the accumulation of genetic aberrations. So, this study aimed to identify the mutational profile of cell cycle checkpoints and regulators in tissue biopsies in Egyptian Colorectal Cancer patients. Material and Methods: Sixty two fresh tissues samples were collected from Egyptian patients with CRC. The libraries were performed using Qiaseq UMI-based targeted panel.The detected genetic variants with an average coverage of 500x were annotated using Ingenuity Variant analysis (IVA) and pathway analysis was performed using Ingenuity Pathway analysis (IPA). Results: Data analysis revealed that TP53&amp; ATM genes; the checkpoints at G1/S and G2/M phases, were highly mutated. They harbored 12 and 9 pathogenic mutations respectively, which cause loss of functionality. The most frequently detected pathogenic variants were c.121delG (58%) in the TP53 &amp; c.640delT (29%) in the ATM. While CHECK2; the checkpoint at G2/M phase, harbored 4 pathogenic variants; c.430delC (16%) was the most detected one. Also, two pathogenic variants were detected in the M phase checkpoint BUB1B and the most frequently detected one was c.1669delA (37%). We also detected pathogenic variants involved in the G1/S phase regulators; SMAD4 (c.1241delT (23%)), CDKN2A (c.238delG (18%)), STK11 (c.340delG (11%)), and CDH1 (c.1955delT (19%)). Other pathogenic variants involved in G2/M phase regulators were also detected; BRCA1 (c.3214delC (16%)) &amp; EP300 (c.4408delA (19%)). Moreover, we detected 2 pathogenic variants in M phase regulator; CDC27 (c.1998delA (7%) &amp; c.2070delA (5%)). Conclusion: Our data showed the deregulated pattern of cell cycle checkpoints and regulators that are crucial for understanding colorectal cancer progression in Egyptian patients. Also, it may help in developing personalized targeted therapies that efficiently target the cell cycle genes mutations, thereby limits the CRC progression in those patients. Citation Format: Amira Salah El-Din Youssef, Mai M. Lotfy, Auhood Nassar, Abdel-Rahman N. Zekri. The mutational pattern of cell cycle checkpoints and regulators in Egyptian colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1964.
乳癌における腫瘍浸潤リンパ球(TIL)の評価 国際TIL作業グループ2014年による推奨
Authors: R Salgado, C Denkert, S Demaria, N Sirtaine, F Klauschen, G Pruneri, S Wienert, G Van Den Eynden, F L Baehner, F Penault-Llorca, E A Perez, E A Thompson, W F Symmans, A L Richardson, J Brock, C Criscitiello, H Bailey, M Ignatiadis, G Floris, J Sparano, Z Kos, T Nielsen, D L Rimm, K H Allison, J S Reis-Filho, S Loibl, C Sotiriou, G Viale, S Badve, S Adams, K Willard-Gallo, S Loi
Journal: Annals of Oncology (2015)
Optimising clinical trials in acute myocardial infarction complicated by cardiogenic shock: a statement from the 2020 Critical Care Clinical Trialists Workshop
Authors: Mattia Arrigo, Susanna Price, David A Baran, Janine Pöss, Nadia Aissaoui, Antoni Bayes-Genis, Laurent Bonello, Bruno François, Etienne Gayat, Martine Gilard, Navin K Kapur, Mahir Karakas, Maciej Kostrubiec, Pascal Leprince, Bruno Levy, Yves Rosenberg, Holger Thiele, Uwe Zeymer, Michael O Harhay, Alexandre Mebazaa
Journal: The Lancet Respiratory Medicine (2021)
Abstract 286: Conception and preparation of new potent antimicrotubule agents
Authors: Mathieu Gagné-Boulet, Chahrazed Bouzriba, Atziri Corin Chavez Alvarez, Sébastien Fortin
Journal: Cancer Research (2021)

Abstract Cancer is still to this day one of the first causes of death in industrialized countries. Despite great progress made so far, there is still no treatment completely efficient and without toxicity. Therefore, the development of new anticancer drugs is sought. To this end, we developed a novel family of potent antimicrotubule agents designated as N-phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs). Our previous structure-activity relationship studies were focused on the aromatic rings A and B of PIB-SOs leaving the sulfonate bridge poorly studied. In the present study, we have designed, prepared and evaluated in vitro new PIB-SO analogs by replacing the sulfonate moiety with a sulfur atom. The new PIB-SO analogs were prepared using classical organic chemistry tools. The antiproliferative activity of PIB-SO analogs was assessed on HT-1080 fibrosarcoma, HT-29 colon adenocarcinoma, M21 skin melanoma and MCF7 estrogen-dependent breast adenocarcinoma. Then, the most potent analogs were assessed for their effect on the cell cycle progression, their capacity to disrupt the microtubules and their ability to bind to the colchicine-binding site (C-BS). Lastly, their theoretical properties were calculated with SwissADME tool. The new PIB-SO analogs bearing the sulfur bridge exhibit antiproliferative activities in the low nanomolar to mid micromolar ranges. The most potent compounds block the cell cycle progression in G2/M phase, disrupt microtubules and bind to the C-BS. Finally, their theoretical pharmacokinetic profiles show that they are potentially suitable for animal experiments. In addition to show that the sulfonate moiety of PIB-SOs can be modulated with a sulfur atom, our study led to the discovery of a new family of potent antimicrotubule agents targeting the C-BS. This study will contribute in the long term to the development of new treatments for cancer patients. Citation Format: Mathieu Gagné-Boulet, Chahrazed Bouzriba, Atziri Corin Chavez Alvarez, Sébastien Fortin. Conception and preparation of new potent antimicrotubule agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 286.
The impact of the presence of Squamous Cell Carcinoma (SCC) variant at Trans-Urethral Resection of the Bladder (TURB) on pathological and follow-up outcomes in patients affected by Non Muscle-Invasive Bladder Cancer (NMIBC)
Authors: F. Chierigo, G. Mantica, F. Ambrosini, R. Malinaric, S. Smelzo, M. Beverini, G. Guano, A. Caviglia, R. Banchero, M. Borghesi, F. Gaboardi, N. Suardi, C. Terrone, Guglielmo Mantica
Journal: European Urology (2021)
Overexpression of L1CAM in non-small cell lung cancer: Clinical implications and molecular characterization.
Authors: Kyoji Hirai, Kiyoshi Koizumi, Shuji Haraguchi, Tomomi Hirata, Iwao Mikami, Tetsuo Kawashima, Shigeki Yamagishi, Yutaka Enomoto, Akima Harada, Kazuo Shimizu
Journal: Cancer Research (2006)

5277  L1CAM (L1) is a 200kD type I transmembrane protein of immunoglobulin superfamily, which is known to play an important role in development of nervous system. On the other hand, recently it has reported that L1 may be associated with poor prognosis of ovarial and uterine cancer (Lancet 2003, Fogel et al). The L1 ectodomain is cleaved by the metalloproteinase ADAM 10 in human tumor cell lines. The biological role for L1 in various cancers remains to be controversial. To investgate L1 involved in progression of nonsmall cell lung cancer, we performed an immunohistochemical study using anti- L1 antibody and L1 mRNA by RT-PCR analysis. In addition, we evaluated ADAM 10 expression using the same samples. We also clarify the mechanism of L1 expression and effect of L1 on cell migration using lung cancer cell lines.   We used surgical resected samples of non small cell lung cancer (50 cases: adeno.41, sq. 9, I:21, II :5, III :24). Using paraffin embedded section, immunohistochemical studies for L1 and ADAM 10 were carried out by LSAB method. L1 and ADAM 10 mRNA in non-cancerous and cancerous tissue was analyzed by RT-PCR. The analysis of ankyrin and F-actin using lung cancer cell lines(PC 9,A 549, PC 14, LCA-1) was carried out. Invasion assay after L1 siRNA treatment was examined. Bronchial glands were weak positive in normal lung tissue. A part of adencarcinoma.and squamous cell carcinoma showed strong positive in cytoplasm. Positive rate was 79.1%(19/24) for stageIII group, 20%(1/5) for stage II group and 57.1% (12/21) for stageIgroup(p=0.03, I + II vs III). Four-year survival rates after operation were 43.9% for L1 -positive group and 91.7% for L1-negative group (p=0.017). L1 and ADAM 10 mRNA could be detected higher in cancerous tissues than in non-cancerous tissues. Co-expression of ankyrin, F-actin and L1 could be observed in lung cancer cell lines.According to invasion assay after L1 siRNA treatment, decreased effect of tumor cell migration was shown. These results suggest that L1 in nonsmall cell lung cancer expresses related to ADAM10,and overexpression of L1 may predict poor prognosis. Additionally, L1 played a role in enhanced tumor cell migration
The Coverage in England of US-Approved Cancer Drugs
Authors: Takanao Hashimoto, Akihiko Ozaki, Tetsuya Tanimoto
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Off-clamp versus on-clamp pure laparoscopic partial nephrectomy: Per-protocol analysis from the CLOCK II randomized clinical trial
Authors: R.G. Bertolo, P. Bove, M. Sandri, C. Cipriani, L. Cindolo, C. Leonardo, P. Parma, M. Falsaperla, D. Veneziano, A. Celia, A. Minervini, A. Antonelli
Journal: European Urology (2021)
Does pay-for-performance improve patient outcomes in acute exacerbation of COPD admissions?
Authors: Philip W Stone, Alexander Adamson, John R Hurst, C Michael Roberts, Jennifer K Quint
Journal: Thorax (2021)

The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD.Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission.28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)).Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions.
Delayed Diagnosis of Breast Cancer as a Cause of Crippling Radical Treatment of Elderly Patients
Authors: E. V. Shivilov, G. E. Kvetenadze, Kh. S. Arslanov, T. V. Pavlova
Journal: Radiology - Practice (2021)

The volume of surgical treatment of breast cancer depends largely on the size of the primary hearth. Malignant neoplasms diagnosed at the initial stage of the disease make it possible to carry out organpreserving operational interventions, which is particularly important in the treatment of elderly patients with concomitant somatic diseases. Clinical observation is presented, which demonstrates the importance of the timely identified and consequences of the late diagnosis of breast cancer in the patient of the elderly, in the form of a crumpled radical operation that affects the quality of life of the patient.
Abstract 2612: Personalized cancer risk and prevention: analysis of risk factors for specific cancers and integration into cancer risk assessment paradigms
Authors: Rosalie K. Elespuru, Catherine Fischer
Journal: Cancer Research (2021)

Abstract Cancer risk assessment is performed generally in relation to assessment of the safety of new medical products or environmental exposures, especially when DNA modification is a factor. The risk assessment paradigms used for products subject to regulatory review are independent of specific cancers, multiple exposures, and individual risk factors. A default cancer risk assessment for regulatory review includes “uncertainty factors” to account for differential susceptibility and other variables involved in extrapolating from experimental systems to human risk. However, there is a growing amount of evidence that suggests differing risk for different types of cancer as well as the importance of combinations of risk factors not limited to genetic or environmental effects. In the era of personalized medicine and cancer genomics, can we begin to assess personalized cancer risk, instead of overall cancer risk? What models would assist in this paradigm shift? There are several cancers for which specific genetic, environmental, viral and other associations have been established and could be used in personalized cancer risk assessments, including colon, liver, and lung cancer. A search was conducted on PubMed for available literature on epidemiology, genetic susceptibility, and risk factors associated with the major types of cancer, including ~25 pathological types of cancer in 17 different organs. Risk factors associated with each included chemical exposures and tobacco, as well as genetic, epigenetic, microbial, viral, dietary, exercise, and other factors known for involvement in the development of cancer in humans. The diversity of cancers and evidence for specific risk factors is summarized. Common risk factors, including smoking and obesity, are supplemented with a substantial set of individual, often non-overlapping risk factors for diverse cancers. Surprisingly, little evidence was found that genetic-environmental interactions are significant risk factors for most cancers. From this assessment we can begin to ask whether and for what cancers a personalized risk approach seems feasible. Disclaimer: The findings and conclusions in this presentation are those of the authors and should not be construed to represent any agency determination or policy. Citation Format: Rosalie K. Elespuru, Catherine Fischer. Personalized cancer risk and prevention: analysis of risk factors for specific cancers and integration into cancer risk assessment paradigms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2612.
Abstract 17: A Noninvasive Method for Measuring the Physiologic Quality of CPR Through Application of Quantitative Waveform Analysis of the Ventricular Fibrillation Electrocardiogram
Authors: David D Salcido, Greggory Housler, James J Menegazzi
Journal: Circulation (2011)

Background: Parameters by which the quality of cardiopulmonary resuscitation (CPR) is commonly gauged, include rate, depth, and chest compression fraction. These measure the process of delivering CPR but give no insight into its physiologic effect. Analysis of electrophysiologic changes during CPR may provide a direct assessment of the impact of CPR that transcends CPR process parameters. Objective: Assess the relationship between coronary perfusion delivered over time (i.e., dose) during CPR and a quantitative measure of the ventricular fibrillation ECG, amplitude spectrum area (AMSA). Methods: Data were pooled retrospectively from 3 swine resuscitation experiments, comprising 63 placebo study arm animals. Swine were sedated, anesthetized, and instrumented with micromanometer-tipped pressure catheters. Coronary perfusion pressure (CPP) was calculated as the difference between the aortic and right atrial pressures at the end of the diastolic phase. Ventricular fibrillation was induced with a transthoracic shock and left untreated for 5 or 8 minutes. CPR was then initiated and continued for 90 seconds (n = 14), 3 minutes (n=25), or 5 minutes (n=24), and was accompanied in 2 series by the administration of epinephrine, vasopressin, propranolol, and sodium bicarbonate. Coronary perfusion dosage was calculated as the area under the CPP curve (CPP-AUC), and AMSA measurements were taken from 5-second periods immediately prior to and immediately following CPR. Delta AMSA was calculated as the difference between the log of the ending and starting AMSA values. Linear regression was used to assess the association between CPP-AUC and Delta AMSA. Results: In univariate models CPP-AUC was significantly inversely associated with Delta AMSA when duration of CPR was 3 minutes (p = 0.02) or 5 minutes (p = 0.002), but not 90 seconds (p = 0.119). In a multivariate linear regression model containing CPP-AUC, duration of CPR, and series, the CPP-AUC was significantly inversely related to Delta AMSA (p &lt; 0.001). Conclusion: The change in the VF waveform during CPR correlates strongly with the dose of perfusion provided over a period of CPR and thus may be a useful measure for estimating CPR quality independent of process measures.
Incidence of Type 2 Diabetes in Individuals With Central Obesity in a Rural Japanese Population
Authors: Hirofumi Ohnishi, Shigeyuki Saitoh, Satoru Takagi, Nobuo Katoh, Yu Chiba, Hiroshi Akasaka, Yosuke Nakamura, Kazuaki Shimamoto
Journal: Diabetes Care (2006)

According to the new International Diabetes Federation (IDF) definition of metabolic syndrome, for a person to be defined as having metabolic syndrome they must have central obesity defined by waist circumference (1). In the definition, there are some ethnic or country-specific differences in the cutoff points of waist circumference, and Japanese cutoff points have been separately established in the IDF definition (≥85 cm for men and ≥90 cm for women). The Japanese Society of Internal Medicine and eight related scientific societies have also jointly announced new Japanese criteria of metabolic syndrome using the same cutoff points of waist circumference (2). However, the impact of central obesity using the cutoff points as a risk of type 2 diabetes is not known.

In this study, we investigated the incidence of type 2 diabetes in citizens of two rural communities in Japan to determine the relationship between type 2 diabetes and central obesity, and we also investigated the independent effects of central obesity compared with those of overall obesity.

The subjects were 348 men and 523 women selected from 938 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, both in 1994 and 2003 or 2004.

The following participants in medical examinations in 1994 were excluded: those with missing data on blood …
Hypothermia Is a Potential New Therapy for a Subset of Tumors with Mutant p53
Authors: Wenwei Hu, Zhaohui Feng
Journal: Cancer Research (2021)

Abstract The tumor suppressor p53 gene is mutated in approximately 50% of all human tumors. Many tumor-associated mutant p53 proteins misfold into a common, denatured conformation and accumulate to high levels in human tumors. In such tumors, these mutant forms of p53 provide a “gain of function” to promote tumor progression. Therefore, targeting mutant p53 has become an attractive approach for cancer therapy. In this issue, the study by Lu and colleagues supports the premise that certain forms of mutant p53 are temperature sensitive in conformation; these forms of p53 are mutant in conformation at physiologic temperature, but can refold into a normal, or “wild-type” conformation at lower temperature (32°C to 34°C). Notably, these temperature-sensitive mutants account for up to 7.5% of all human tumors that carry mutant p53, so this fraction of patients is estimated to be quite significant. Results from this study show that employing therapeutic hypothermia to reduce the core temperature of mice bearing tumors with these temperature-sensitive mutant forms of p53 (ts mutant p53) causes ts mutant p53 to switch to a wild-type conformation in tumors, inhibiting tumor growth. Moreover, combining hypothermia with chemotherapy leads to durable remission of such tumors, with no obvious toxicity to normal tissues. See related article by Lu et al., p. 3905