tbuckley/cabot-search huggingface dataset:
Abstract P2-17-02: Locoregional therapy targeted at the primary tumour improves overall survival in patients presenting with <i>de novo</i> stage IV metastatic breast cancer: A systematic review and meta-analysis of real-world data with 201598 patients
Authors: Salim Tayeh, Ritika Gera, Hiba El Hage Chehade, Umar Wazir, Abdul Kasem, Kefah Mokbel
Journal: Cancer Research (2020)

Abstract Background: De novo stage IV metastatic breast cancer is a complex disease that is traditionally treated using systemic therapy. There is mounting evidence that locoregional therapy (LRT), defined as resection of the primary tumour and/or localised radiotherapy, could be associated with survival improvements. We aimed to conduct a meta-analysis to inform decision making. Methods: Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis was undertaken to assess whether LRT of the primary tumour in metastatic breast cancer prolongs survival. Results: 48 studies met the criteria for analysing the efficacy of all locoregional treatments (radiotherapy and/or surgery) and 44 studies were suitable for the analysis of surgery-only treatment of the primary. Studies were analysed for the impact of LRT on survival. All LRT resulted in a significant 32.9% reduction in mortality with LRT (N=48; HR=0.671: 95% CI 0.624-0.721). Primary resection alone resulted in a significant 36.9% mortality (N=44; HR=0.631: 95% CI 0.591-0.674). Conclusions: This is the largest meta-analysis regarding this question to date. LRT seems to improve overall survival in stage IV disease at initial diagnosis and should be considered in selected patients after a multidisciplinary discussion. Citation Format: Salim Tayeh, Ritika Gera, Hiba El Hage Chehade, Umar Wazir, Abdul Kasem, Kefah Mokbel. Locoregional therapy targeted at the primary tumour improves overall survival in patients presenting with de novo stage IV metastatic breast cancer: A systematic review and meta-analysis of real-world data with 201598 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-02.
Clinical relevance of miRNA expression in metastatic melanoma
Authors: M. F. Segura, J. Zakrzewski, I. Belitskaya-Levy, A. Gaziel, M. Kushnir, M. Hoshen, D. Hanniford, D. Cohen, I. Osman, E. Hernando
Journal: Journal of Clinical Oncology (2009)

9006 Background: We recently reported the identification of a specific miRNA cluster frequently overexpressed in melanoma which enhances the metastatic behavior (Segura et al., 2009. PNAS. In press). In this study, we aim to define the clinical relevance of miRNA expression, in particular whether miRNAs can serve as prognostic biomarkers for melanoma patients. Methods: Total RNA was extracted from formalin-fixed paraffin embedded (FFPE) tissue samples from 61 metastatic melanoma specimens (25 lymph node, 16 soft tissue/skin, 13 brain and 7 visceral) accrued by the NYU Interdisciplinary Melanoma Cooperative Group (IMCG). RNA was hybridized into miRNA arrays (miRdicatorTM, Rosetta Genomics, Inc) containing probes for more than 600 miRNA sequences, including all the human miRNAs in the 9.0 version of miRBase. The Significance Analysis of Microarrays (SAM) was used to identify miRNAs significantly associated with survival, and the False Discovery Rate (FDR) approach was used to adjust for multiple comparisons. Results: We identified a signature of 18 miRNAs, whose up-regulation significantly associates with better prognosis (increased overall survival and post-recurrence survival) using the FDR of 0%. Quantitative RT-PCR on the same tissues has verified the array results in 15 out of 15 miRNAs analyzed. Some of these miRNAs were significantly associated with stage at recurrence, while others significantly correlated with the site of metastasis (i.e. visceral, brain, soft-tissue). Using cross-validation, we selected a miRNA signature consisting of 10 of these significant miRNAs with lowest misclassification error in predicting 1.5-year post-recurrence survival. We are currently validating these findings in a separate cohort of metastatic patients. Furthermore, we are investigating whether these ‘protective' miRNAs can be detected in the corresponding primary lesions and thus, whether they already hold prognostic value at early stages of the disease. Conclusions: Our data suggest a role for miRNAs as melanoma biomarkers, and support the development of miRNA- based monitoring assays. These analyses are also expanding our understanding of the molecular alterations underlying melanoma progression, by revealing miRNAs whose down-regulation associates with a more aggressive biological behavior. [Table: see text]
Abstract #692: Predictive value of orotate phosphoribosyltransferase expression for treatment outcomes in patients with advanced gastric cancer treated with 3-weekly S-1 plus cisplatin chemotherapy
Authors: Keun-Wook Lee, Hye Seung Lee, In Sil Choi, Ki Hwan Kim, Yu Jung Kim, Jee Hyun Kim, Jong Seok Lee
Journal: Cancer Research (2009)

Background: S-1 has recently been shown to improve clinical outcomes of patients with metastatic or relapsed gastric cancer (MRGC), especially when combined with cisplatin. In Japanese patients, 5-weekly regimen [S-1 80mg/m2/day (days 1~21) plus cisplatin 60mg/m2/day (day 8)] has been commonly used. However, it is still controversial which combination schedule of S-1 and cisplatin is the most appropriate for the improvement of anti-tumor activity and patients\#8217; compliance. Thus, this study was performed to evaluate the efficacy and toxicity of a 3-weekly S-1 plus cisplatin regimen. Predictive value of protein expressions, which are associated with fluoropyrimidine and cisplatin metabolism, was also evaluated. Methods: Forty-six chemotherapy-naive MRGC patients were consecutively enrolled. S-1 (80 mg/m2/day) was given orally on days 1~14 and cisplatin (60 mg/m2) was administrated i.v. on day 1. All patients had Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0~2 and had at least one measurable lesion. Expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), excision repair cross complementation 1 (ERCC1), Fanconi anemia complementation group D2 (FANCD2), glutathione S-transferase-P (GSTP), and X-ray repair cross-complementing group 1 (XRCC1) were determine by immunohistochemical staining. Results: The median age of enrolled patients was 61 years. Overall response rate was 48%; one patient (2%) showed complete response and 21 patients (46%) had partial responses. The median progression free survival (PFS) and overall survival (OS) were 21.1 and 68.3 weeks, respectively. Common hematologic toxicities were anemia (93%) and neutropenia (61%). However, grade 3/4 anemia and neutropenia developed only in 11% and 24%, respectively. Common non-hematologic toxicities were anorexia (70%), nausea (63%), asthenia (57%), vomiting (39%), stomatitis (41%) and diarrhea (35%). Grade 3/4 non-hematologic toxicities included anorexia (22%), asthenia (13%), nausea (7%), and diarrhea (7%). The expression level of OPRT was classified into 2 groups based on intensity and percentage of stained cancer cells. Patients with higher OPRT levels in tumor tissue had superior PFS [23.3 vs. 14.1 weeks (median)] and OS [72.4 vs. 55.4 weeks] to those with lower OPRT levels. Expression levels of other proteins were not predictive of treatment outcomes. In multivariate analysis, both ECOG PS \#8804;1 (vs. 2) and higher OPRT levels (vs. lower levels) were independently associated with prolonged PFS and OS (P   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 692.
Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study
Authors: Shanu Modi, Haeseong Park, Rashmi K. Murthy, Hiroji Iwata, Kenji Tamura, Junji Tsurutani, Alvaro Moreno-Aspitia, Toshihiko Doi, Yasuaki Sagara, Charles Redfern, Ian E. Krop, Caleb Lee, Yoshihiko Fujisaki, Masahiro Sugihara, Lin Zhang, Javad Shahidi, Shunji Takahashi
Journal: Journal of Clinical Oncology (2020)

Trastuzumab deruxtecan (T-DXd, formerly DS-8201a) is a novel human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload. A dose escalation and expansion phase I study evaluated the safety and activity of T-DXd in patients with advanced HER2-expressing/mutated solid tumors. Here, results for T-DXd at the recommended doses for expansion (RDE) in patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization-) breast cancer (ClinicalTrials.gov identifier: NCT02564900) are reported.Eligible patients had advanced/metastatic HER2-low-expressing breast cancer refractory to standard therapies. The RDE of 5.4 or 6.4 mg/kg T-DXd were administered intravenously once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. Antitumor activity and safety were assessed.Between August 2016 and August 2018, 54 patients were enrolled and received ≥ 1 dose of T-DXd at the RDE. Patients were extensively pretreated (median, 7.5 prior therapies). The confirmed objective response rate by independent central review was 20/54 (37.0%; 95% CI, 24.3% to 51.3%) with median duration of response of 10.4 months (95% CI, 8.8 month to not evaluable). Most patients (53/54; 98.1%) experienced ≥ 1 treatment-emergent adverse event (TEAE; grade ≥ 3; 34/54; 63.0%). Common (≥ 5%) grade ≥ 3 TEAEs included decreases in neutrophil, platelet, and WBC counts; anemia; hypokalemia; AST increase; decreased appetite; and diarrhea. Three patients treated at 6.4 mg/kg suffered fatal events associated with T-DXd-induced interstitial lung disease (ILD)/pneumonitis as determined by an independent adjudication committee.The novel HER2-targeted ADC, T-DXd, demonstrated promising preliminary antitumor activity in patients with HER2-low breast cancer. Most toxicities were GI or hematologic in nature. ILD is an important identified risk and should be monitored closely and proactively managed.
Annals Story Slam - Innovations: Practices That Build Trust - Voices of Duke Health Listening Booth and Podcast
Authors: Anton Zuiker
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Voices of Duke Health Listening Booth and PodcastFREEAnton ZuikerAnton ZuikerDuke University, Durham, North Carolina (A.Z.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0008 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Voices of Duke Health Listening Booth and Podcast "Innovations: Practices That Build Trust - Voices of Duke Health Listening Booth and Podcast," by Anton Zuiker (Duration 4:13)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Duke University, Durham, North Carolina (A.Z.)Current Author Address: Anton Zuiker, 732 Smith Level Road, Chapel Hill, NC 27516; e-mail, anton.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Improving Gender Equality in the Surgical Workplace
Authors: Roisin Finn, Lara Prisco, Mario Ganau
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study cohort
Authors: Alessandro Mengozzi, Domenico Tricò, Lorenzo Nesti, John Petrie, Kurt Højlund, Asimina Mitrakou, Michael Krebs, Andrea Mari, Andrea Natali
Journal: Metabolism (2020)
Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration
Authors: Ajit Magadum, Neha Singh, Ann Anu Kurian, Irsa Munir, Talha Mehmood, Kemar Brown, Mohammad Tofael Kabir Sharkar, Elena Chepurko, Yassine Sassi, Jae Gyun Oh, Philyoung Lee, Celio X.C. Santos, Avital Gaziel-Sovran, Guoan Zhang, Chen-Leng Cai, Changwon Kho, Manuel Mayr, Ajay M. Shah, Roger J. Hajjar, Lior Zangi
Journal: Circulation (2020)

Background: The adult mammalian heart has limited regenerative capacity, mostly attributable to postnatal cardiomyocyte cell cycle arrest. In the last 2 decades, numerous studies have explored cardiomyocyte cell cycle regulatory mechanisms to enhance myocardial regeneration after myocardial infarction. Pkm2 (Pyruvate kinase muscle isoenzyme 2) is an isoenzyme of the glycolytic enzyme pyruvate kinase. The role of Pkm2 in cardiomyocyte proliferation, heart development, and cardiac regeneration is unknown. Methods: We investigated the effect of Pkm2 in cardiomyocytes through models of loss (cardiomyocyte-specific Pkm2 deletion during cardiac development) or gain using cardiomyocyte-specific Pkm2 modified mRNA to evaluate Pkm2 function and regenerative affects after acute or chronic myocardial infarction in mice. Results: Here, we identify Pkm2 as an important regulator of the cardiomyocyte cell cycle. We show that Pkm2 is expressed in cardiomyocytes during development and immediately after birth but not during adulthood. Loss of function studies show that cardiomyocyte-specific Pkm2 deletion during cardiac development resulted in significantly reduced cardiomyocyte cell cycle, cardiomyocyte numbers, and myocardial size. In addition, using cardiomyocyte-specific Pkm2 modified RNA, our novel cardiomyocyte-targeted strategy, after acute or chronic myocardial infarction, resulted in increased cardiomyocyte cell division, enhanced cardiac function, and improved long-term survival. We mechanistically show that Pkm2 regulates the cardiomyocyte cell cycle and reduces oxidative stress damage through anabolic pathways and β-catenin. Conclusions: We demonstrate that Pkm2 is an important intrinsic regulator of the cardiomyocyte cell cycle and oxidative stress, and highlight its therapeutic potential using cardiomyocyte-specific Pkm2 modified RNA as a gene delivery platform.
Annals Story Slam - Innovations: Practices That Build Trust - Prairie Parkway LGBTQ Clinic
Authors: Kyle Christiason
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Prairie Parkway LGBTQ ClinicFREEKyle Christiason, MDKyle Christiason, MDUnity Point Health (K.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0003 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Prairie Parkway LGBTQ Clinic "Innovations: Practices That Build Trust - Prairie Parkway LGBTQ Clinic," by Kyle Christiason, MD (Duration 3:55)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Unity Point Health (K.C.)Current Author Address: Kyle Christiason, MD; e-mail, kyle.[email protected]org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1KeywordsLGBTQ ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Abstract 10602: A Machine-Learning Model in Predicting Hemodynamically Significant Coronary Artery Disease: A Prospective Cohort Study
Authors: Yan Liu, Xuming Dai, Hope Wolf, Tyrone C Wade, George A Stouffer
Journal: Circulation (2018)

Background: Noninvasive cardiac imaging modalities have been widely used for detection of Coronary Artery Disease (CAD) and clinical decision making, however, there are still significant limitation...
Analysis of TGFBR1 gene in colorectal carcinoma
Authors: Jose L. Soto, Adela Castillejo, Noemi Garrigos, Angeles Gomez, Miriam Garcia-Bautista, Pilar Garcia-Morales, Miguel Saceda, Javier Gallego, Francisco X. Real, Alfredo Carrato
Journal: Cancer Research (2004)

5077  Background: TGFβ is one of the most potent inhibitors of the proliferation in different cell types. TGFβ is transduced by two transmembrane serine-threonine receptors. It has been confirmed that abnormalities of this signaling pathway may predispose to or cause cancer. Somatic alterations of TGFBR1 gene have been found in different tumors: point mutations were found in breast and ovarian tumors and promoter hypermethylation in gastric cancer. Moreover, a tumor susceptibility allele in a common polymorphism at TGFBR1 exon 1 has been also described. Aim: The purpose of this study was to determine the implication of TGFBR1 gene in colorectal cancer analyzing genetic and epigenetic somatic alterations and genotyping the polymorphism at exon 1. Methods: A consecutive series of 63 surgically resected tumors from colorectal cancer patients were included in this study. Two TGFBR1 gene surrounding microsatellite markers (at 9q22.3) were used to analyze loss of heterozygosity. LOH and genotyping analysis were performed by PCR and capillary electrophoresis. Promoter hypermethylation of the gene was analyzed by HpaII/MspI DNA digestion followed by PCR. Quantitative real time PCR was performed to study relative TGFBR1 mRNA gene expression. Finally, statistical analysis of collected molecular data and clinical variables (age, gender, tumor location and tumor stage) was done. Results: The polymorphism analysis rendered the following results: 71.4% (45 /63) of individuals were TβRI9A/TβRI9A; 23.8% (15/63) heterozygous TβRI9A/TβRI6A; and 4.8% (3/63) homozygous TβRI6A/TβRI6A. LOH was found in 18 out of 55 informative cases (32.7%). No TGFBR1 promoter hypermethylation was detected in any of the 31 normal/tumor pairs analyzed. The gene expression study revealed unexpected results: we found no significant changes in gene expression levels in tumor tissues respect to their counterparts normal mucosa in 49,2% of the analyzed cases (30/61). Loss of mRNA expression in tumors was detected only in 9.8% of cases (6/61). The remainder 25 tumors, (41%) showed a significant increase of mRNA levels. Univariate analysis revealed significant statistical association between loss of gene expression and males (p= 0,015). Tumors from homozygous individuals TβRI6A/TβRI6A undergo LOH more frequently (p=0,025). No association was found between LOH and loss of expression. Tumors from heterozygous individuals showed a trend to be more aggressive (stages III and IV). Conclusions: The wide spectrum of molecular and clinical variables analyzed in this study allowed us to obtain the novel data shown here. New questions have arised and need to be answered. The frequent increase of mRNA gene expression needs to be confirmed at protein level and the functional significance of this alteration should be evaluated. The statistical associations related to the polymorphism point to interesting prognostic implications.
Stress Allostasis in Substance Use Disorders: Promise, Progress, and Emerging Priorities in Clinical Research
Authors: Gaylen E. Fronk, Sarah J. Sant'Ana, Jesse T. Kaye, John J. Curtin
Journal: Annual Review of Clinical Psychology (2020)

Clinicians and researchers alike have long believed that stressors play a pivotal etiologic role in risk, maintenance, and/or relapse of alcohol and other substance use disorders (SUDs). Numerous seminal and contemporary theories on SUD etiology posit that stressors may motivate drug use and that individuals who use drugs chronically may display altered responses to stressors. We use foundational basic stress biology research as a lens through which to evaluate critically the available evidence to support these key stress-SUD theses in humans. Additionally, we examine the field's success to date in targeting stressors and stress allostasis in treatments for SUDs. We conclude with our recommendations for how best to advance our understanding of the relationship between stressors and drug use, and we discuss clinical implications for treatment development.
Sensitization profile of cricket food-allergic or cricket tolerant patients in an entomophagous population in Niamey, Niger
Authors: Romy Gadisseur, Tahirou Hamidou, Etienne Cavalier, Justine Courtois, Xavier vanderbrempt, Stephanie Tollenaere, Maizoumbou, Jacquier, Laouali
Journal: Allergy (2019)