tbuckley/cabot-search huggingface dataset:
Impact of EGFR-TKI Treatment on the Tumor Immune Microenvironment in <i>EGFR</i> Mutation–Positive Non–Small Cell Lung Cancer
Authors: Kohsuke Isomoto, Koji Haratani, Hidetoshi Hayashi, Shigeki Shimizu, Shuta Tomida, Takashi Niwa, Toshihide Yokoyama, Yasushi Fukuda, Yasutaka Chiba, Ryoji Kato, Junko Tanizaki, Kaoru Tanaka, Masayuki Takeda, Takashi Ogura, Tadashi Ishida, Akihiko Ito, Kazuhiko Nakagawa
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The impact of EGFR tyrosine kinase inhibitors (TKI) on the tumor immune microenvironment (TME) in non–small cell lung cancer (NSCLC) is unclear. Experimental Design: We retrospectively identified 138 patients with EGFR-mutated NSCLC who underwent rebiopsy after progression during EGFR-TKI treatment. PD-L1 and CD73 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density at baseline and after progression were determined by IHC. Tumor mutation burden (TMB) was determined by next-generation sequencing. Results: The proportion of patients with a PD-L1 expression level of ≥50% (high) increased from 14% before to 28% after EGFR-TKI (P = 0.0010). Whereas CD8+ and FOXP3+ TIL densities were significantly lower after EGFR-TKI treatment than before, CD8+ TIL density was maintained in tumors with a high PD-L1 expression level. Expression of CD73 in tumor cells after EGFR-TKI treatment was higher than that before in patients with a high PD-L1 expression level. TMB tended to be higher after EGFR-TKI treatment than before (3.3→4.1 mutations/Mbp, P = 0.0508). Median progression-free survival for subsequent treatment with antibodies to PD-1 was longer for patients with a high than for those with a low PD-L1 expression after EGFR-TKI (7.1 vs. 1.7 months, P = 0.0033), and two of five patients whose PD-L1 expression level changed from low to high after EGFR-TKI treatment achieved a PFS of &amp;gt;6 months. Conclusions: EGFR-TKI treatment was associated with changes in the TME of EGFR-mutated NSCLC, and such changes may provide clues for optimization of subsequent PD-1 inhibitor treatment.
The Effect of Coconut Oil Consumption on Cardiovascular Risk Factors
Authors: Nithya Neelakantan, Jowy Yi Hoong Seah, Rob M. van Dam
Journal: Circulation (2020)

Coconut oil is high in saturated fat and may, therefore, raise serum cholesterol concentrations, but beneficial effects on other cardiovascular risk factors have also been suggested. Therefore, we conducted a systematic review of the effect of coconut oil consumption on blood lipids and other cardiovascular risk factors compared with other cooking oils using data from clinical trials.We searched PubMed, SCOPUS, Cochrane Registry, and Web of Science through June 2019. We selected trials that compared the effects of coconut oil consumption with other fats that lasted at least 2 weeks. Two reviewers independently screened articles, extracted data, and assessed the study quality according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The main outcomes included low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), total cholesterol, triglycerides, measures of body fatness, markers of inflammation, and glycemia. Data were pooled using random-effects meta-analysis.16 articles were included in the meta-analysis. Results were available from all trials on blood lipids, 8 trials on body weight, 5 trials on percentage body fat, 4 trials on waist circumference, 4 trials on fasting plasma glucose, and 5 trials on C-reactive protein. Coconut oil consumption significantly increased LDL-cholesterol by 10.47 mg/dL (95% CI: 3.01, 17.94; I2 = 84%, N=16) and HDL-cholesterol by 4.00 mg/dL (95% CI: 2.26, 5.73; I2 = 72%, N=16) as compared with nontropical vegetable oils. These effects remained significant after excluding nonrandomized trials, or trials of poor quality (Jadad score <3). Coconut oil consumption did not significantly affect markers of glycemia, inflammation, and adiposity as compared with nontropical vegetable oils.Coconut oil consumption results in significantly higher LDL-cholesterol than nontropical vegetable oils. This should inform choices about coconut oil consumption.
Sphingosine Kinase 1 (SPHK1) Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models
Authors: L. Formisano, L. Nappi, R. Rosa, V. Damiano, R. Marciano, C. D'Amato, C. Carlomagno, G. Troncone, S. De Placido, R. Bianco
Journal: Annals of Oncology (2012)
Abstract 216: Therapeutic Hypothermia Alone and in Combination With Preconditioning Improves Long Term Survival During Resuscitation of Hemorrhagic Shock
Authors: Wangde Dai, Jianru Shi, Juan Carreno, Robert A Kloner
Journal: Circulation (2019)

Background: We investigated the effects of hypothermia treatment alone and in combination with experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Previously we showed that RIPC alone improved survival. Methods: In the hypothermia alone study, adult Sprague Dawley rats (both genders) were randomized to hypothermia (n=16) or control group (n=15); in a combination study, rats were randomized to hypothermia plus RIPC (n=11) or control group (n=10). Rats were anesthetized with intraperitoneal ketamine/xylazine. Therapeutic hypothermia (Thermosuit) was started at 5 minutes after mean blood pressure (MBP) reached 30 mmHg. Core temperature was maintained at ~ 32 °C until blood volume was fully restored. RIPC was induced by 4 cycles of inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute deflation of the cuffs prior to hemorrhagic shock. In the control group, body temperature was maintained at 37 °C during the procedure. Hemorrhagic shock was induced by withdrawing blood from the carotid artery. Target mean blood pressure of 30 mmHg was maintained for 30 minutes followed by reinfusion of shed blood within the next 30 min. Rats were allowed recovery and the primary endpoint was survival rate at 6 weeks. Results: In the setting of hypothermia alone, 4 of 15 (26.7 %) rats in the control group and 11 of 16 (68.8 %; p = 0.032) rats in the hypothermia group survived at 6 weeks. In the combination study, 1 of 10 (10 %) rats in the control group and 7 of 11 (63.6 %; p = 0.024) rats in the hypothermia plus RIPC group survived at 6 weeks. Kaplan Meier Survival Curves are shown in Fig1. Conclusions: Hypothermia alone and combination with RIPC significantly improved long term survival in rats subjected to hemorrhagic shock. Hypothermia and RIPC did not show survival rates greater than hypothermia alone.
Molecular Complete Remission Following Ivosidenib in a Patient With an Acute Undifferentiated Leukemia
Authors: Sandipkumar H. Patel, Sumithira Vasu, Ling Guo, Olivia Lemaster, John C. Byrd, Alison Walker
Journal: Journal of the National Comprehensive Cancer Network (2020)

Acute undifferentiated leukemia (AUL) is a subtype of acute leukemias of ambiguous lineage. There is no standard treatment approach for AUL, although acute lymphoblastic leukemia–like regimens for induction therapy have been used. Additional data suggest that AUL may be better treated as acute myeloid leukemia (AML), given their similarities in genetic, cytogenetic, and gene expression patterns. Somatic mutations of IDH1 are found in 7% to 14% of patients with AML; however, the patient in this study was the first patient with IDH1 -mutated AUL treated with ivosidenib. In this case, a woman aged 39 years was found to have anemia and thrombocytopenia after presenting to her primary care physician with fatigue, weight loss, and persistent infections. During further workup of the cytopenia, she was diagnosed with AUL and received 7+3 (daunorubicin, 60 mg/m 2 /d intravenously on days 1–3, and cytarabine, 100 mg/m 2 24-hour continuous intravenous infusion on days 1–7) due to the presence of the IDH1 mutation. Bone marrow biopsy performed on day 14 of 7+3 showed persistent disease, and ivosidenib was initiated due to severe HLA alloimmunization (panel-reactive antibody, 100%) and significant bleeding complications. The patient achieved a complete morphologic and molecular remission on ivosidenib monotherapy despite critical bleeding complications during induction. Targeted therapy using ivosidenib may represent an encouraging therapeutic option in patients with AUL and IDH1 mutations. Additional evaluation of ivosidenib in this subgroup of patients with AUL is needed.
Functional Analysis of Reprimo as a Suppressor Gene in Gastric Cancer
Authors: A. Ooki, K. Yamashita, K. Yamaguchi, M. Asayama, S. Kadowaki, H. Hara, T. Yamada-murano, M. Arima, M. Tada, M. Watanabe
Journal: Annals of Oncology (2012)
Influence of gastrectomy for gastric cancer treatment on faecal microbiome and metabolome profiles
Authors: Pande Putu Erawijantari, Sayaka Mizutani, Hirotsugu Shiroma, Satoshi Shiba, Takeshi Nakajima, Taku Sakamoto, Yutaka Saito, Shinji Fukuda, Shinichi Yachida, Takuji Yamada
Journal: Gut (2020)

Recent evidence points to the gut microbiome's involvement in postoperative outcomes, including after gastrectomy. Here, we investigated the influence of gastrectomy for gastric cancer on the gut microbiome and metabolome, and how it related to postgastrectomy conditions.We performed shotgun metagenomics sequencing and capillary electrophoresis time-of-flight mass spectrometry-based metabolomics analyses on faecal samples collected from participants with a history of gastrectomy for gastric cancer (n=50) and compared them with control participants (n=56).The gut microbiota in the gastrectomy group showed higher species diversity and richness (p<0.05), together with greater abundance of aerobes, facultative anaerobes and oral microbes. Moreover, bile acids such as genotoxic deoxycholic acid and branched-chain amino acids were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p<0.05, q<0.1, LDA>2.0), as were also Kyoto Encyclopedia of Genes and Genomes modules involved in nutrient transport and organic compounds biosynthesis (LEfSe: p<0.05, q<0.1, LDA>2.0).Our results reveal alterations of gut microbiota after gastrectomy, suggesting its association with postoperative comorbidities. The multi-omic approach applied in this study could complement the follow-up of patients after gastrectomy.
A conductive cell-delivery construct as a bioengineered patch that can improve electrical propagation and synchronize cardiomyocyte contraction for heart repair
Authors: Shanglin Chen, Meng-Hsuan Hsieh, Shu-Hong Li, Jun Wu, Richard D. Weisel, Yen Chang, Hsing-Wen Sung, Ren-Ke Li
Journal: Journal of Controlled Release (2020)
Diagnostic tests for tuberculous meningitis
Authors: Angharad G Davis, Robert J Wilkinson
Journal: The Lancet Infectious Diseases (2020)

Tuberculous meningitis is the most serious manifestation of tuberculosis, with mortality in approximately 50% of HIV co-infected people. 1 Marais S Pepper DJ Schutz C Wilkinson RJ Meintjes G Presentation and outcome of tuberculous meningitis in a high HIV prevalence setting. PLoS One. 2011; 6e20077 Crossref PubMed Scopus (69) Google Scholar A major factor contributing to the poor outcome of tuberculous meningitis is delayed diagnosis due to a lack of rapid, accurate diagnostic tests. Until recently, these tests were restricted to smear microscopy of cerebrospinal fluid (CSF) and microbiological culture. The former tends operationally to be of low sensitivity and the latter often renders a result too late to be clinically meaningful. The diagnosis of drug-resistant disease presents further difficulties. Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation studyXpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. Full-Text PDF Open AccessXpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy studyXpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required. Full-Text PDF Open Access
Synergistic Anti-Tumor Effect of Sorafenib in Combination with AKT Inhibitors in Hepatocellular Carcinoma
Authors: W.-C. Feng, C.-H. Hsu, S.-D. Lin, H.-H. Lin, D.-W. Hsu, C.-C. Huang, L.-P. Chow, A.-L. Cheng
Journal: Annals of Oncology (2012)
The creatine–phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis
Authors: Vassilis Papalazarou, Tong Zhang, Nikki R. Paul, Amelie Juin, Marco Cantini, Oliver D. K. Maddocks, Manuel Salmeron-Sanchez, Laura M. Machesky
Journal: Nature Metabolism (2020)
Phase IB Dose-Escalation Study of BEZ235 or BKM120 in Combination with Paclitaxel (PTX) in Patients With Advanced Solid Tumors
Authors: L. Dirix, M. Schuler, J. Machiels, D. Hess, A. Awada, N. Steeghs, L. Paz-Ares, R. von Moos, B. Rabault, J. Rodon
Journal: Annals of Oncology (2012)
Early intervention in psychosis in low‐ and middle‐income countries: a WPA initiative
Authors: Swaran P. Singh, Afzal Javed
Journal: World Psychiatry (2020)

Specialist early intervention in psychosis (EIP) services have been considered the "most positive development in mental health services since the beginning of community care"1. The development and implementation of specialist EIP services in high-income countries was predicated on the "critical period hypothesis" , which argued that poor outcomes in psychosis accumulated in the first 2-5 years since onset of the disorder2, and that longer duration of untreated psychosis (DUP) was associated with poorer outcomes3. Early intervention incorporates three different paradigms: assertive and high-quality evidence-based care by specialist teams in first-episode psychosis; early detection of untreated cases in the community (i.e., shortening of DUP); and interventions for young people at clinical high risk (CHR) – also known as ultra high risk (UHR) – for developing a psychotic disorder4, 5. The most consistent evidence is from trials of specialist EIP care versus treatment as usual, which shows better short-to-medium clinical and functional outcomes for those receiving EIP care6, as well as cost-effectiveness of EIP7, while the evidence of specific effective CHR/UHR interventions to prevent the emergence of psychosis remains unclear8, 9. Almost 80% of all patients with first-episode psychosis live in low- and middle-income countries (LMICs), where mental health services are scarce and most people do not get any form of mental health care10. Mental health treatment gap – the difference between those needing mental health care and those receiving it – is extraordinarily high in LMICs11. In the absence of adequate care, many people with psychotic disorders in LMICs end up restrained, neglected or simply abandoned. Despite the burden of untreated or inadequately treated psychotic disorders, the resource scarcity in LMICs – inadequate funding, lack of basic services and shortage of trained professionals – means that it is not feasible to set up specialized EIP services when even basic care for mental disorders is lacking. However, while "Western" models of care cannot be just translocated to LMICs, it should be possible to incorporate the principles and "therapeutic ingredients" of early intervention into routine mental health settings in LMICs, at all levels of care – primary (community), secondary and specialist tertiary (where these exist)12, 13. To meet this challenge, the WPA has set up an Expert International Advisory Panel to develop a set of priorities, guidelines and recommendations for early intervention in LMIC settings. An initial meeting was held in May 2019 in Coventry, UK. At this meeting, a small group of experts agreed on the needs and priorities that could guide the development of early intervention strategies in LMICs within the existing constraints of scarce resources. The group is planning a larger meeting in early 2020, where formal guidelines and recommendations will be agreed upon and adopted as part of the WPA initiative.
Neurologic and oncologic features of Erdheim–Chester disease: a 30-patient series
Authors: Ankush Bhatia, Vaios Hatzoglou, Gary Ulaner, Raajit Rampal, David M Hyman, Omar Abdel-Wahab, Benjamin H Durham, Ahmet Dogan, Neval Ozkaya, Mariko Yabe, Kseniya Petrova-Drus, Katherine S Panageas, Anne Reiner, Marc Rosenblum, Eli L Diamond
Journal: Neuro-Oncology (2020)

Abstract Background Erdheim–Chester disease (ECD) is a rare histiocytic neoplasm characterized by recurrent alterations in the MAPK (mitogen-activating protein kinase) pathway. The existing literature about the neuro-oncological spectrum of ECD is limited. Methods We present retrospective clinical, radiographic, pathologic, molecular, and treatment data from 30 patients with ECD neurohistiocytic involvement treated at a tertiary center. Results Median age was 52 years (range, 7–77), and 20 (67%) patients were male. Presenting symptoms included ataxia in 19 patients (63%), dysarthria in 14 (47%), diabetes insipidus in 12 (40%), cognitive impairment in 10 (33%), and bulbar affect in 9 (30%). Neurosurgical biopsy specimens in 8 patients demonstrated varied morphologic findings often uncharacteristic of typical ECD lesions. Molecular analysis revealed mutations in BRAF (18 patients), MAP2K1 (5), RAS isoforms (2), and 2 fusions involving BRAF and ALK. Conventional therapies (corticosteroids, immunosuppressants, interferon-alpha [IFN-α], cytotoxic chemotherapy) led to partial radiographic response in 8/40 patients (20%) by MRI with no complete responses, partial metabolic response in 4/16 (25%), and complete metabolic response in 1/16 (6%) by 18F-fluorodeoxyglucose (FDG)-PET scan. In comparison, targeted (kinase inhibitor) therapies yielded partial radiographic response in 10/27 (37%) and complete radiographic response in 14/27 (52%) by MRI, and partial metabolic response in 6/25 (24%) and complete metabolic response in 17/25 (68%) by FDG-PET scan. Conclusions These data highlight underrecognized symptomatology, heterogeneous neuropathology, and robust responses to targeted therapies across the mutational spectrum in ECD patients with neurological involvement, particularly when conventional therapies have failed.
Inhibiting Translation Elongation with SVC112 Suppresses Cancer Stem Cells and Inhibits Growth in Head and Neck Squamous Carcinoma
Authors: Stephen B. Keysar, Nathan Gomes, Bettina Miller, Brian C. Jackson, Phuong N. Le, J. Jason Morton, Julie Reisinger, Tugs-Saikhan Chimed, Karina E. Gomez, Cera Nieto, Barbara Frederick, Gijsbertus J. Pronk, Hilary L. Somerset, Aik-Choon Tan, Xiao-Jing Wang, David Raben, Tin Tin Su, Antonio Jimeno
Journal: Cancer Research (2020)

Cancer stem cells (CSC) drive growth, therapy resistance, and recurrence in head and neck squamous cell carcinoma (HNSCC). Regulation of protein translation is crucial for normal stem cells and CSCs; its inhibition could disrupt stemness properties, but translation inhibitors are limited clinically due to toxicity. SVC112 is a synthetic derivative of bouvardin, a plant-derived translation elongation inhibitor. SVC112 had greater antiproliferative effects on HNSCC cells compared with the FDA-approved translation inhibitor omacetaxine mepesuccinate (HHT). SVC112 preferentially inhibited cancer cells compared with patient-matched cancer-associated fibroblasts, whereas HHT was equally toxic to both. SVC112 reduced sphere formation by cell lines and CSCs. SVC112 alone inhibited the growth of patient-derived xenografts (PDX), and SVC112 combined with radiation resulted in tumor regression in HPV-positive and HPV-negative HNSCC PDXs. Notably, CSC depletion after SVC112 correlated with tumor response. SVC112 preferentially impeded ribosomal processing of mRNAs critical for stress response and decreased CSC-related proteins including Myc and Sox2. SVC112 increased cell-cycle progression delay and slowed DNA repair following radiation, enhancing colony and sphere formation radiation effects. In summary, these data demonstrate that SVC112 suppresses CSC-related proteins, enhances the effects of radiation, and blocks growth of HNSCC PDXs by inhibiting CSCs. SIGNIFICANCE: Inhibiting protein elongation with SVC112 reduces tumor growth in head and neck squamous cell carcinoma and increases the effects of radiation by targeting the cancer stem cell pool.
A Phase II Multicenter Randomized Open-Label Study of Oral Steroid Sulphatase (STS) Inhibitor Irosustat (BN83495) Versus Megestrol Acetate (MA) in Women with Advanced/Recurrent Endometrial Cancer (EC)
Authors: P. Pautier, F. Joly Lobbedez, B. Melichar, E. Kutarska, G. Hall, N. Reed
Journal: Annals of Oncology (2012)
Safety and activity of alflutinib in patients with advanced EGFR T790M mutation non-small cell lung cancer who progressed after EGFR-TKI therapy
Authors: Y.-K. Shi, S. Zhang, X. Hu, J. Feng, Z. Ma, J. Zhou, N. Yang, L. Wu, W. Liao, X. Han, Z. Wang, X. Zhang, S. Qin, K. Ying, J. Feng, J. Fang, L. Liu, Y. Jiang
Journal: Annals of Oncology (2019)
P-0207 Colorectal Cancer in The Elderly Moroccan Patients
Authors: Khaoula Daoudi, Nezar Bouyahia, Khalid El Haoudi, Hafida Benhammane, Sami Aziz Brahmi, Fatima Zahra El M'rabet, Karima Oualla, Samia Arifi, Nawfel Mellas, Khalid Maazaz, Omar El Mesbahi
Journal: Annals of Oncology (2012)
High Expression of Acetyl-Tubulin as a Chemoresistant Biomarker in Human Docetaxel-Resistance Prostate Cancer Cells
Authors: T.-C. Hour, H.-L. Wu, S.-J. Chuang, C.-Y. Lu, C.-Y. Huang, W.-J. Wu, Y.-S. Pu
Journal: Annals of Oncology (2012)
Primary Resistance to First-Line Bevacizumab in Metastatic Colorectal Cancer: Implications on Prognosis
Authors: E. Maccaroni, R. Giampieri, M. Scartozzi, M. Del Prete, A. Bittoni, L. Faloppi, M. Bianconi, S. Cascinu
Journal: Annals of Oncology (2012)
Experimental animal models of coronary microvascular dysfunction
Authors: Oana Sorop, Jens van de Wouw, Selena Chandler, Vahagn Ohanyan, Johnathan D Tune, William M Chilian, Daphne Merkus, Shawn B Bender, Dirk J Duncker
Journal: Cardiovascular Research (2020)

Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischaemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed 'ischaemia and no obstructive coronary artery disease' (INOCA). Notwithstanding the high prevalence of INOCA, effective treatment remains elusive. Although to date there is no animal model for INOCA, animal models of CMD, one of the hallmarks of INOCA, offer excellent test models for enhancing our understanding of the pathophysiology of CMD and for investigating novel therapies. This article presents an overview of currently available experimental models of CMD-with an emphasis on metabolic derangements as risk factors-in dogs, swine, rabbits, rats, and mice. In all available animal models, metabolic derangements are most often induced by a high-fat diet (HFD) and/or diabetes mellitus via injection of alloxan or streptozotocin, but there is also a wide variety of spontaneous as well as transgenic animal models which develop metabolic derangements. Depending on the number, severity, and duration of exposure to risk factors-all these animal models show perturbations in coronary microvascular (endothelial) function and structure, similar to what has been observed in patients with INOCA and comorbid conditions. The use of these animal models will be instrumental in identifying novel therapeutic targets and for the subsequent development and testing of novel therapeutic interventions to combat ischaemic heart disease, the number one cause of death worldwide.