tbuckley/cabot-search huggingface dataset:
M1a disease should be reconsidered in esophageal cancer staging system from the perspective of treatment response and survival after definitive concurrent chemoradiotherapy.
Authors: Tae Ryong Chung, Jie-Hyun Kim, Ik Jae Lee, Yona Cho, Da Hyun Jung, Jae Jun Park, Young Hoon Youn, Hyojin Park
Journal: Journal of Clinical Oncology (2019)

13 Background: M1a node involvement based on the 6th edition AJCC staging system was classified as regional node involvement in the 7th edition of esophageal squamous cell carcinoma (ESCC). However, the clinical significance of M1a node involvement based on the 6th edition staging system has not been well established. Thus, we analyzed the prognostic value of M1a node in patients of ESCC after definitive chemoradiotherapy (CCRT). Methods: A total of 188 ESCC patients had M0 disease based on the 7th edition AJCC classification, of which 31 (16.5%) of them were reclassified to the M1a patient group under the 6th edition AJCC classification. After definitive CCRT, we compared the basic characteristics of two groups, analyzed the rate of complete remission (CR), recurrence, finally assessed overall survival (OS), and disease-free survival (DFS) of each group. Results: Among 31 patients reclassified to M1a disease, 21 patients (67.7%) had subclavian nodes and 10 patients (32.3%) had celiac nodes. The median follow-up period was 18.3 months. The M1a group showed a significantly lower survival rate not only in median OS (M1a 16.4 months, M0 42.7 months, P = 0.015), but also in 5-year OS (M1a 10.8%, M0 41.2%). Three of 31 patients (9.7%) in the M1a group achieved CR, while 41 of 157 patients (26.1%) in the M0 group achieved CR ( P = 0.048). However, there was no recurrence in the M1a group after achieved CR during follow-up period. Conclusions: Among ESCC patients after completing definitive CCRT, M1a patients according to the 6th AJCC staging system showed lower CR rate and OS rate compared with M0 disease patients. M1a nodes should be differentiated from regional node involvement.
Epidemiological Study on β-Thalassemia in Algeria
Authors: Fatiha Grifi, A Djenouni, S Bougherira, MT Abad, C Boucherit, N Boudjerra, N Zidani, C Aboura, A Aribi, M Belhani, S Nekkal, H Bouaricha, Fz Benhassine, R Ahmed Nacer, F Tensaout, N Ait amer, RM Hamladji, S Hamdi, S Zatout, N Sidi Mansour, Z Ouchenane, SE Belakehal, H Mansour, Y Ghassoul, M Djilali, Fz Ardjoun, N Lakhdari, L Touati, N Bouterfa, R Fenghour, H Ait Ali, A Graine, M Allouda, A Bouacha, D Saidi, W Sfaoui, H Touhami, N Bouchair, N Hamani, M Saidi, R Nacib, A Bekache, R Dridi, N Mesli, N Houti, Y Ouarlhent, S Chichoune, N Mehalhal, Z Zouaoui, A Benallal, MA Bekadja, Malek Benakli
Journal: Blood (2018)
BF‐200 ALA凝胶与MAL乳膏治疗BCC的对比
Authors: C.A. Morton, R. Dominicus, P. Radny, T. Dirschka, A. Hauschild, U. Reinhold, R. Aschoff, M. Ulrich, S. Keohane, S. Ekanayake‐Bohlig, S. Ibbotson, R. Ostendorf, C. Berking, D. Gröne, H.J. Schulze, H.M. Ockenfels, V. Jasnoch, H. Kurzen, M. Sebastian, H. Stege, P. Staubach‐Renz, G. Gupta, F. Hübinger, I. Ziabreva, B. Schmitz, A. Gertzmann, H. Lübbert, R.‐M. Szeimies
Journal: British Journal of Dermatology (2018)
Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia
Authors: Lai N Chan, Seyedmehdi Shojaee, Christian Hurtz, Franziska Auer, Zhengshan Chen, Kadriye Nehir Cosgun, Huimin Geng, Teresa Sadras, Deborah L White, Markus Muschen
Journal: Blood (2018)
Association of Care at Minority-Serving vs Non–Minority-Serving Hospitals With Use of Palliative Care Among Racial/Ethnic Minorities With Metastatic Cancer in the United States
Authors: Alexander P. Cole, David-Dan Nguyen, Akezhan Meirkhanov, Mehra Golshan, Nelya Melnitchouk, Stuart R. Lipsitz, Kerry L. Kilbridge, Adam S. Kibel, Zara Cooper, Joel Weissman, Quoc-Dien Trinh
Journal: JAMA Network Open (2019)

It is not known whether racial/ethnic differences in receipt of palliative care are attributable to different treatment of minorities or lower utilization of palliative care at the relatively small number of hospitals that treat a large portion of minority patients.To assess the association of receipt of palliative care among patients with metastatic cancer with receipt of treatment at minority-serving hospitals (MSHs) vs non-MSHs.This retrospective cohort study used Participant Use Files of the National Cancer Database, a prospectively maintained, hospital-based cancer registry consisting of all patients treated at more than 1500 US hospitals, to collect data from individuals older than 40 years with metastatic prostate, lung, colon, and breast cancer, diagnosed from January 1, 2004, to December 31, 2015. Data were accessed in October 2017, and the analysis was performed in July 2018.Hospitals in the top decile in terms of the proportion of black and Hispanic patients for each cancer type were defined as MSHs.A multilevel logistic regression model that estimated the odds of palliative care was fit, adjusting for year of diagnosis, sex, race/ethnicity, insurance, income, educational level, and cancer type, with an interaction term between cancer type and MSH status and a hospital-level random intercept to account for unmeasured hospital characteristics.A total of 601 680 individuals (mean [SD] age, 67.4 [11.4] years; 95% CI, 67.2-67.6 years; 314 279 [52.2%] male; 475 039 [78.9%] white) were studied. In total, 130 813 patients (21.7%) received palliative care, ranging from 102 019 (25.4%) with lung cancer to 9966 (11.1%) with colon cancer. In total, 16 435 black individuals (20.0%) and 3551 Hispanic individuals (15.9%) received palliative care vs 106 603 non-Hispanic white individuals (22.5%) (P < .001). The MSH patients were less likely than the non-MSH patients to receive palliative care, regardless of race/ethnicity (12 692 [18.0%] vs 118 121 [22.3%]; P = .002). In an adjusted analysis, treatment at an MSH had a statistically significant association with lower odds of receiving palliative care (odds ratio, 0.67; 95% CI, 0.53-0.84).Although the factors associated with minority patients' receipt of palliative care are complex, in this study, treatment at MSHs was associated with significantly lower odds of receiving any palliative care in an adjusted analysis, but black and Hispanic race/ethnicity was not. These findings suggest that the site of care is associated with race/ethnicity-based differences in palliative care.
Long-term Outcomes of Antiviral Therapy in Patients With Advanced Chronic HBV Infection
Authors: Hye Won Lee, Jun Yong Park, Sang Gyune Kim, Won Young Tak, Hyung Joon Yim, Byoung Kuk Jang, Moon Young Kim, Byung Ik Kim, Jin-Woo Lee, Ki Tae Yoon, Jae Youn Cheong, So Young Kwon, Tae Yeob Kim, Si Hyun Bae, Yeon Seok Seo, Jung Hyun Kwon, Dong Joon Kim, Ja-Kyung Kim, Soung Won Jeong, Sungmin Myoung, Sang Hoon Ahn, Kwang-Hyub Han
Journal: Clinical Gastroenterology and Hepatology (2019)
Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001
Authors: O. Hamid, C. Robert, A. Daud, F.S. Hodi, W.J. Hwu, R. Kefford, J.D. Wolchok, P. Hersey, R. Joseph, J.S. Weber, R. Dronca, T.C. Mitchell, A. Patnaik, H.M. Zarour, A.M. Joshua, Q. Zhao, E. Jensen, S. Ahsan, N. Ibrahim, A. Ribas
Journal: Annals of Oncology (2019)

Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.
Genomic and immune infiltration differences between MSI and MSS GI tumors.
Authors: Yulia Newton, Justin Golovato, Iain Beehuat Tan, Justina Yick Ching Lam, Guo Yu, Si-Lin Koo, Clarinda Chua, Joe Poh Sheng Yeong, Christine Ping, Anders Skanderup, Jonathan Göke, Mark Johnson, Shahrooz Rabizadeh, J Zachary Sanborn, Stephen Charles Benz, Charles Joseph Vaske, Christopher Szeto
Journal: Journal of Clinical Oncology (2019)

528 Background: Dysregulation of DNA mismatch repair pathway can lead to microsatellite instability in many GI tumors, and microsatellite instability is an important diagnostic and prognostic marker. Microsatellite instable (MSI) tumors comprise about 15% of colorectal malignancies and can be found in other gastrointestinal (GI) tumor types. We present results of analysis of genomic and immune infiltration differences between MSI and microsatellite stable (MSS) GI tumors spanning multiple cancer types. Methods: A total of 521 GI patients with deep whole exome sequencing (WES) of tumor and blood samples, and whole transcriptomic sequencing (RNA-Seq) (∼200M reads per tumor) were available for this analysis from a commercial database. Variant calling was performed through joint probabilistic analysis of tumor and normal DNA reads, with germline status of variants being determined by heterozygous or homozygous alternate allele fraction in the germline sample. Results: Gene expression and pathway analysis found significantly higher immune signaling in MSI cohort and higher metabolic signaling in MSS cohort. We also found upregulation of structural cellular integrity pathways in MSI tumors. Per-sample deconvolution of immune infiltration using cell type gene markers shows some MSI samples with high CD8 T-cells. Co-expression analysis of checkpoint and TME genes shows higher correlation of FOXP3 and CTLA4 in the MSS cohort compared to the MSI samples, whereas correlation between FOXP3 and PDL1 is decreased. TIM3, LAG3, and OX40 are significantly more expressed in MSI samples than MSS samples. Within the subset of colorectal tumors, additional checkpoints are significantly differentially overexpressed in MSI malignancies. 50 somatic variants are significantly differential in MSI tumors. Conclusions: MSI tumors demonstrably exhibit higher immune signaling, with many immune and checkpoint markers expressed at higher levels in MSI tumors. Some cellular integrity pathways also appear to be up in MSI cohort. A number of potentially important somatic variants are associated with MSI samples.
CXCL12 mediates the migration of metastatic breast cancer cells through the activation of PI-3 kinase/AKT and Focal adhesion kinase
Authors: Richard Akomeah, K. Fareed N. Arthur, Joshua C. M. Willaims, Samuel E. Adunyah
Journal: Cancer Research (2004)

860  Human IL-17A is a cytokine of about 30 kDa produced by memory activated T-cells though its receptor is ubiquitously expressed. Its major role is regulation of production of immune response and hematopoietic-related cytokines by which it fine-tunes all the phases of hematopoiesis and immune response. It is involved in human diseases including inflammation, arthritis, aging, and cancers of the breast and prostate and lymphoma. However, the mechanisms by which it accomplishes its effects are not known. Our laboratory has observed that in human U937 leukemia cells, IL-17A activates multiple signaling cascades including the PK-C and Raf/MAPK-mediated pathways and the PI-3K/Akt pathway. In the current study, we demonstrate that IL-17 enhances rapid (within 60 sec) association between Src Kinases (Lck and Fynn) and the p85 component of PI-3K, suggesting that these Src Kinases mediate PI-3K activation in response to IL-17A. To further understand the role of PI-3K/Akt and Src kinases in the biological effects of IL-17A, we investigated the effects of Src Kinase inhibitor (PP2) or the PI-3K inhibitors (LY) on the ability of IL-17A to stimulate production of cytokines. U937 cells were treated with IL-17A (100 ng/ml) in the absence or presence of a specific inhibitor (either PP2 or LY) for days. Culture media were assayed for cytokine production using the Panomics Cytokine Antibody Arrays. In the absence of inhibitors, IL-17A alone stimulated differential expression (2 to 8-fold increase) of Th1 and Th2-type cytokines and chemokines within 24 to 48 hours. The stimulatory effects of IL-17A were markedly reduced or blocked by either PP2 or LY. These results suggest that Lck and Fynn differentially mediate stimulation of cytokine production by IL-17A via the PI-3K/Akt signaling pathway, implicating Src Kinases and the PI-3K/Akt in the immune response processes evoked by IL-17A. Because NF-kB transcriptional factor is suspected to play a role in IL-17A-mediated signaling, we assessed cells for NF-kB activation in response to IL-17A using transcriptional assays, Panomics Protein/DNA Transcriptional Arrays and WB detection of p-IkB. To our surprise, NF-kB was not activated by IL-17A. In contract, a number of transcriptional factors include Bm2, STAT3, STAT1, Egr-1, Smad3, CRE and GRE were markedly activated by this cytokine, suggesting that perhaps transcriptional factors other than NF-kB mediate regulation of gene expression by IL-17A. Future studies are in progress to determine the relevance of these results regarding the potential role of IL-17A in cancer. Supported by NCI U54 and SCORE Grants.
A low percentage of metastases in deep brain and temporal lobe structures
Authors: Ted K Yanagihara, J Ricardo McFaline-Figueroa, Nicholas J Giacalone, Albert W Lee, Vikram Soni, Mark E Hwang, Kristin T Hsieh, Anurag Saraf, Cheng-Chia Wu, Daniel Yang, Patrick Y Wen, Hani Ashamalla, Ayal A Aizer, Tony J C Wang, Raymond Y Huang
Journal: Neuro-Oncology (2019)

Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed across the brain and that several additional areas may be avoided in WBRT based on a low risk of developing BM. We contoured 2757 lesions in a large, single-institution database of patients with newly diagnosed BM. BM centroids were mapped onto a standard brain atlas of 55 anatomic subunits and the observed percentage of BM was compared with what would be expected based on that region’s volume. A region of interest (ROI) analysis was performed in a validation cohort of patients from 2 independent institutions using equivalence and one-sample hypothesis tests. The brainstem and bilateral thalami, hippocampi, parahippocampal gyri, amygdala, and temporal poles had a cumulative risk of harboring a BM centroid of 4.83% in the initial cohort. This ROI was tested in 157 patients from the validation cohort and was found to have a 4.1% risk of developing BM, which was statistically equivalent between the 2 groups (P < 1 × 10–6, upper bound). Several critical brain structures are at a low risk of developing BM. A risk-adapted approach to WBRT is worthy of further investigation and may mitigate the toxicities of conventional radiation.
Neoadjuvant treatment in a Mexican cohort of patients with locally advanced rectal cancer: Oncologic outcomes and prognostic factors.
Authors: ZULEYMA NIETO GARCIA, Edgar Omar Martos Armendáriz, Vanessa Rosas Camargo, Christian Haydeé Flores Balcázar, Mónica Isabel Meneses Medina, Noel Salgado Nesme, Artemio García Badiola, Mariana Licano Zubiate, Laura Esther Luna González, Juan Alberto Garay Mora, Armando Gamboa Domínguez, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2019)

704 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy (CT) is the standard of care for locally advanced rectal cancer (LARC). Total neoadjuvant therapy (TNT) consists of induction CT followed by CRT prior to surgery. This is an alternative strategy recommended in guidelines. Objective: To describe neoadjuvant strategies, oncologic outcomes and prognostic factors in a cohort of patients (pts) with LARC treated at a referral center in Mexico City. Methods: We retrospectively reviewed medical records from pts with LARC (T3-T4 or N+) treated with any neoadjuvant strategy at Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” from January 2010 to December 2015. Clinical and pathological information was registered. Survival was estimated by Kaplan-Meier method. Univariate analysis for prognostic factors was performed and survival was compared by the log rank test. Results: 43 pts were included. Median age was 62 y/o (19-83), 51% were female. Clinical stage (CS) II 9% and CS III 91%. 36 pts were T3-4 and N+(86%). Localization was lower third 30%, middle third 56% and upper third 12%. 63% were moderately differentiated adenocarcinoma. 84% had TNT: induction CT with FOLFOX-4 regimen for 3 months followed by CRT (50.4 Gy in 28 fractions concurrently with fluoropyrimidines) and TME. Surgery: ultra-low anterior resection (AR) 48%, low AR 28% and abdominoperineal resection 24%. One patient did not accept surgery. Of the 32 pts with ultra-low and low AR, 94% had protective ileostomy. The pathologic complete response (pCR) ypT0ypN0 rate was 45% (19/42). Median follow-up was 48 months. There were 8/42 recurrences (19%): local-only 2.3%, systemic only 12% and both 5%. None of the pts with pCR recurred. All pts with residual nodal disease recurred (5/5). The 5-year relapse-free survival rate was 73%. There were 6 deaths, one patient died without disease. The 5-year overall survival rate was 83%. Conclusions: In pts with LARC the TNT is associated with high rates of pCR and favorable oncological outcomes. pCR and residual nodal disease after neoadjuvant therapy were strongly associated with recurrence and survival.
Abstract 18530: Outcomes of Intracoronary Vascular Brachytherapy for Treatment of In-stent Restenosis in the Contemporary Drug-Eluting Stent Era
Authors: Kyle D Buchanan, M Chadi Alraies, Toby Rogers, Arie Steinvil, Eddie Koifman, Linzhi Xu, Rebecca Torguson, William Suddath, Augusto Pichard, Itsik Ben-Dor, Lowell F Satler, Ron Waksman
Journal: Circulation (2017)

Introduction: In-stent restenosis (ISR) of drug-eluting stents (DES) continues to be a therapeutic challenge and its frequency increases over time. Intracoronary vascular brachytherapy (VBT) was in...
High Comorbidity Burden and Rates of Severe Reactions in Young Patients With Peanut Allergy
Authors: Todd A. Mahr, Jay A. Lieberman, Tmirah Haselkorn, Varsha Damle, Yasser Ali, Arul Chidambaram, Karin Rosén, J. Wesley Sublett
Journal: Journal of Allergy and Clinical Immunology (2019)
Informed consent for endoscopic procedures in Portugal – do we need a thoroughly detailed consent form?
Authors: N Almeida, M Areia, C Chagas, R Cardoso, M Dinis-Ribeiro
Journal: Endoscopy (2019)

Endoscopy is an invaluable tool for all Gastroenterologists but most importantly it is a crucial procedure/method in screening, diagnosis and management of gastrointestinal diseases which in turn affect a relevant proportion of citizens. The number and technical difficulty of endoscopic procedures have greatly increased in the past two decades, and even the simpler ones are not purely diagnostic examinations which are exempt from risks [1]. A small but real risk is present in all endoscopic procedures, even if there are no additional diagnostic (e. g., biopsies) or therapeutic manoeuvres (such as polypectomy).
Multiplatform profiling of pancreatic neuroendocrine tumors (PanNETs) identifies novel co-occurring pathogenic alterations and associations with clinicopathologic factors.
Authors: Michelle Guan, Jun Gong, Andrew Eugene Hendifar, Richard Tuli, Veronica Placencio-Hickok, Joseph Bender, Edik Matthew Blais, Emanuel Petricoin
Journal: Journal of Clinical Oncology (2019)

211 Background: We correlated genomic, proteomic, and molecular pathway alterations with clinicopathologic factors and identified novel co-occurring pathogenic alterations of potential clinical relevance to PanNET management through multi-omic profiling. Methods: Perthera, Inc. deploys an IRB-approved registry that was utilized in partnership with PanCAN’s “Know Your Tumor” program. PanNETs having undergone molecular profiling for precision matched therapeutic purposes were screened. We performed correlative analyses by pairwise comparisons between pathogenic alterations or altered molecular pathways and clinicopathologic variables. Hierarchical clustering was used to visualize associations. The Kaplan-Meier method was used to estimate overall survival (OS) and survival differences across variables were analyzed by the log-rank test. Results: We included 33 patients with predominantly locally advanced and metastatic PanNETs from 12/2014-1/2018. Chromatin remodeling pathway and MEN1 alterations by next-generation sequencing (NGS) were less associated with having high-grade PanNETs, while MEN1 alterations were also less associated with metastatic disease at diagnosis (all Fisher’s exact two-tailed p ≤ 0.05). Several molecular pathway or pathogenic alterations correlated with worse OS: DNA repair pathway (log-rank p = 0.0022), RB1 alterations by NGS (p = 0.018), and TP53 alterations by NGS (p = 0.01). There were several significant co-occurring alterations (Fisher’s exact p ≤ 0.05): ERCC1 expression by immunohistochemistry (IHC) and DAXX (NGS), RB1 (NGS) and DNA repair pathway (NGS), and TS (IHC) and cyclin-dependent kinase pathway (NGS). Having an altered chromatin remodeling pathway was less associated with having an altered receptor tyrosine kinase (RTK) signaling pathway (Fisher’s exact p ≤ 0.05). Conclusions: We identified several molecular signatures of potential clinical significance for therapeutic targeting and prognostication in PanNETs warranting prospective validation. Our findings are hypothesis generating and can inform larger molecular profiling efforts in PanNETs.
Effect of levothyroxine supplementation on pregnancy loss and preterm birth in women with subclinical hypothyroidism and thyroid autoimmunity: a systematic review and meta-analysis
Authors: Meng Rao, Zhengyan Zeng, Fang Zhou, Huawei Wang, Jiang Liu, Rui Wang, Ya Wen, Zexing Yang, Cunmei Su, Zhenfang Su, Shuhua Zhao, Li Tang
Journal: Human Reproduction Update (2019)

BACKGROUNDSubclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes such as pregnancy loss and preterm birth. However, the ability of levothyroxine (LT4) supplementation to attenuate the risks of these outcomes remains controversial.
Refractory and Relapse Predictive Biomarkers in Hodgkin Lymphoma and Potential Directed-Therapy Targets
Authors: Angélica María Gamboa-Cedeño, Mariángeles Castillo, Victoria Otero, Natalia Paola Schutz, Dorotea Beatriz Fantl, Federico Jauk, Hernán García Rivello, Marta Zerga, Silvana Cugliari, Erica Rojas-Bilbao, Myriam Nuñez, Stella Ranuncolo
Journal: Blood (2018)