tbuckley/cabot-search huggingface dataset:
Enhanced antitumor effect and lower viral reactivation with high doses of <i>ex vivo</i> expanded NK cells administered after haploidentical transplantation.
Authors: Stefan O. Ciurea, Rima Saliba, Doris Soebbing, Gabriela Rondon, Kai Cao, Sairah Ahmed, Amanda Leigh Olson, Qaiser Bashir, Indreshpal Kaur, Elizabeth J. Shpall, Dean Anthony Lee, Richard E. Champlin
Journal: Journal of Clinical Oncology (2019)

74 Background: NK cells have potent antitumor and antiviral effects. We hypothesized that multiple infusions of high doses of mb-IL21 ex vivo expanded NK cells administered peri-transplant will enhance graft-versus-leukemia effect and decrease viral reactivation. Methods: In the phase 1 dose escalation study patients received NK cells starting at 1x10 5 to 1x10 8 /Kg/dose (N = 13). No dose limiting toxicities were observed. In the phase 2 study, 12 patients with myeloid malignancies received mbIL-21 ex vivo expanded NK cells at dose 1x10 8 NK cells/kg with a K562 feeder cell system and with 41BB. NK cells were generated from peripheral blood mononuclear cells of the same donor and infused fresh on day -2, and cryopreserved on day +7 and +28. Conditioning regimen consisted of melphalan, fludarabine and TBI. All patients had bone marrow graft. Here we report updated results of all patients treated to date on this study. Results: Twenty-five patients (18 AML/MDS and 7 CML) were treated to date. The median age was 45 years, the median follow-up of survivors was 28 months. 16/18 AML/MDS patients had high-risk disease. No adverse effects occurred. Engraftment was achieved in all 24 evaluable patients after a median of 19 days. The cumulative incidence (CI) of grade 2 aGVHD was 38% at day 100. No chronic GVHD was observed. The CI of TRM was 21% at 2 years. The CI of relapse at 1 year was 8%. The 2-years PFS was 66%. Ten patients reactivated CMV. Immunologic reconstitution of T cell subsets showed a 5.7 fold higher number of NK cells on day 28 in patients who received highest NK cell doses vs. others. A matched-pair analysis done with an independent CIBMTR cohort of patients who received either MAC (N = 61) or RIC (N = 57), showed a significantly improvement in relapse rate and PFS in favor of patients treated on trial. Conclusions: Administration of higher doses of NK cells was associated with higher NK cell numbers early post-transplant, suggesting that a dose-dependent effect could be achieved. A low relapse rate and lower viral reactivation post-transplant continues to be seen, suggesting that NK cells exert both anti-tumor and antiviral effects in this setting. Clinical trial information: NCT01904136.
Unpacking the null: a post-hoc analysis of a cluster-randomised controlled trial of the WHO Safe Childbirth Checklist in Uttar Pradesh, India (BetterBirth)
Authors: Megan Marx Delaney, Kate A Miller, Lauren Bobanski, Shambhavi Singh, Vishwajeet Kumar, Ami Karlage, Danielle E Tuller, Atul A Gawande, Katherine E A Semrau
Journal: The Lancet Global Health (2019)

A coaching-based implementation of the WHO Safe Childbirth Checklist in Uttar Pradesh, India, improved adherence to evidence-based practices, but did not reduce perinatal mortality, maternal morbidity, or maternal mortality. We examined facility-level correlates of the outcomes, which varied widely across the 120 study facilities.We did a post-hoc analysis of the coaching-based implementation of the WHO Safe Childbirth Checklist in Uttar Pradesh. We used multivariable modelling to identify correlations between 30 facility-level characteristics and each health outcome (perinatal mortality, maternal morbidity, or maternal mortality). To identify contexts in which the intervention might have had an effect, we then ran the models on data restricted to the period of intensive coaching and among patients not referred out of the facilities.In the multivariable context, perinatal mortality was associated with only 3 of the 30 variables: female literacy at the district level, geographical location, and previous neonatal mortality. Maternal morbidity was only associated with geographical location. No facility-level predictors were associated with maternal mortality. Among facilities in the lowest tertile of birth volume (<95 births per month), our models estimated perinatal mortality was 17 (95% CI 11·7-24·8) per 1000 births in the intervention group versus 38 (31·6-44·8) per 1000 in the control group (p<0·0001).Mortality was not directly associated with measured facility-level indicators but was associated with general risk factors. The absence of correlation between expected predictors and patient outcomes and the association between improved outcomes and the intervention in smaller facilities suggest a need for additional measures of quality of care that take into account complexity.Bill & Melinda Gates Foundation.
Stretchable ECM Patch Enhances Stem Cell Delivery for Post‐MI Cardiovascular Repair
Authors: In Gul Kim, Mintai P. Hwang, Jin Sil Park, Su‐Hyun Kim, Jung‐Hyun Kim, Hyo Jin Kang, Ramesh Subbiah, Ung Hyun Ko, Jennifer H. Shin, Chong‐Hyun Kim, Donghoon Choi, Kwideok Park
Journal: Advanced Healthcare Materials (2019)

Abstract Current cell‐based therapies administered after myocardial infarction (MI) show limited efficacy due to subpar cell retention in a dynamically beating heart. In particular, cardiac patches generally provide a cursory level of cell attachment due to the lack of an adequate microenvironment. From this perspective, decellularized cell‐derived ECM (CDM) is attractive in its recapitulation of a natural biophysical environment for cells. Unfortunately, its weak physical property renders it difficult to retain in its original form, limiting its full potential. Here, a novel strategy to peel CDM off from its underlying substrate is proposed. By physically stamping it onto a polyvinyl alcohol hydrogel, the resulting stretchable extracellular matrix (ECM) membrane preserves the natural microenvironment of CDM, thereby conferring a biological interface to a viscoelastic membrane. Its various mechanical and biological properties are characterized and its capacity to improve cardiomyocyte functionality is demonstrated. Finally, evidence of enhanced stem cell delivery using the stretchable ECM membrane is presented, which leads to improved cardiac remodeling in a rat MI model. A new class of material based on natural CDM is envisioned for the enhanced delivery of cells and growth factors that have a known affinity with ECM.
Reply to Yubo Yang, Xin Wei, and Ping Han's Letter to the Editor re: Roger Li, Philippe E. Spiess, Scott M. Gilbert, Andrea Necchi. Towards Personalized Neoadjuvant Therapy for Muscle-invasive Bladder Cancer. Eur Urol 2019;76:4–6
Authors: Roger Li, Philippe E. Spiess, Scott M. Gilbert, Andrea Necchi
Journal: European Urology (2019)
COTI-2, A Novel Thiosemicarbazone Derivative, Exhibits Antitumor Activity in HNSCC through p53-dependent and -independent Mechanisms
Authors: Antje Lindemann, Ameeta A. Patel, Natalie L. Silver, Lin Tang, Zhiyi Liu, Li Wang, Noriaki Tanaka, Xiayu Rao, Hideaki Takahashi, Nakachi K. Maduka, Mei Zhao, Tseng-Cheng Chen, WeiWei Liu, Meng Gao, Jing Wang, Steven J. Frank, Walter N. Hittelman, Gordon B. Mills, Jeffrey N. Myers, Abdullah A. Osman
Journal: Clinical Cancer Research (2019)

TP53 mutations are highly prevalent in head and neck squamous cell carcinoma (HNSCC) and associated with increased resistance to conventional treatment primarily consisting of chemotherapy and radiation. Restoration of wild-type p53 function in TP53-mutant cancer cells represents an attractive therapeutic approach and has been explored in recent years. In this study, the efficacy of a putative p53 reactivator called COTI-2 was evaluated in HNSCC cell lines with different TP53 status.Experimental Design: Clonogenic survival assays and an orthotopic mouse model of oral cancer were used to examine in vitro and in vivo sensitivity of HNSCC cell lines with either wild-type, null, or mutant TP53 to COTI-2 alone, and in combination with cisplatin and/or radiation. Western blotting, cell cycle, live-cell imaging, RNA sequencing, reverse-phase protein array, chromatin immunoprecipitation, and apoptosis analyses were performed to dissect molecular mechanisms.COTI-2 decreased clonogenic survival of HNSCC cells and potentiated response to cisplatin and/or radiation in vitro and in vivo irrespective of TP53 status. Mechanistically, COTI-2 normalized wild-type p53 target gene expression and restored DNA-binding properties to the p53-mutant protein in HNSCC. In addition, COTI-2 induced DNA damage and replication stress responses leading to apoptosis and/or senescence. Furthermore, COTI-2 lead to activation of AMPK and inhibition of the mTOR pathways in vitro in HNSCC cells.COTI-2 inhibits tumor growth in vitro and in vivo in HNSCC likely through p53-dependent and p53-independent mechanisms. Combination of COTI-2 with cisplatin or radiation may be highly relevant in treating patients with HNSCC harboring TP53 mutations.
Oral Sessions, Monday, 12 October 2009
Journal: Intensive Care Medicine (2009)

CONTEXT.Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive diagnostic investigation that may cause respiratory deterioration in hypoxemic patients.Recently introduced noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL in cancer patients. OBJECTIVE.To determine whether FO-BAL in cancer patients with hypoxemic ARF increases the need for mechanical ventilation (MV).A major secondary objective was to assess diagnostic benefits from FO-BAL added to noninvasive tests. DESIGN.Multicenter randomized controlled trial.SETTING.16 intensive care units in France.PATIENTS.219 cancer patients with ARF of undetermined etiology not on MV at inclusion. INTERVENTIONS.Early FO-BAL.Noninvasive diagnostic tests were performed in both groups.MAIN OUTCOME MEASURES.The primary endpoint was the need for MV.The major secondary endpoint was whether noninvasive testing without FO-BAL was not inferior to noninvasive testing with FO-BAL.Sample size calculations were performed for both these endpoints.RESULTS.15% of patients had solid tumors and 85% had hematological malignancies.There were 36.1% neutropenic patients and 25% hematopoietic stem-cell transplant recipients.Treatments at ICU admission included antibacterial (80%), antifungal (29%), and antiviral (15%) agents.We found no significant differences regarding the need for MV (35.4 and 38.7% of patients in the invasive and noninvasive groups, respectively), proportion of patients with no diagnosis (20.4 vs. 21.7%), or 28-day mortality (29 vs. 33%).In the invasivestrategy group, the cause of ARF was identified by FO-BAL (performed within 1 (0-1) day after ICU admission) only in 18% of patients and by noninvasive tests only in 45% of patients (P \ 0.0001).CONCLUSIONS.FO-BAL in critically ill cancer patients with ARF did not increase the need for MV.Noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL for identifying the cause of ARF.Patients with negative noninvasive tests on day 3 did not benefit from second-line FO-BAL.(ClinicalTrials.govnumber, NCT00248443).
Efficacy of Short-term Treatment of Internet and Computer Game Addiction
Authors: Klaus Wölfling, Kai W. Müller, Michael Dreier, Christian Ruckes, Oliver Deuster, Anil Batra, Karl Mann, Michael Musalek, Andreas Schuster, Tagrid Lemenager, Sara Hanke, Manfred E. Beutel
Journal: JAMA Psychiatry (2019)

<h3>Importance</h3> Internet and computer game addiction represent a growing mental health concern, acknowledged by the World Health Organization. <h3>Objective</h3> To determine whether manualized cognitive behavioral therapy (CBT), using short-term treatment for internet and computer game addiction (STICA), is efficient in individuals experiencing internet and computer game addiction. <h3>Design, Setting, and Participants</h3> A multicenter randomized clinical trial was conducted in 4 outpatient clinics in Germany and Austria from January 24, 2012, to June 14, 2017, including follow-ups. Blinded measurements were conducted. A consecutive sample of 143 men was randomized to the treatment group (STICA; n = 72) or wait-list control (WLC) group (n = 71). Main inclusion criteria were male sex and internet addiction as the primary diagnosis. The STICA group had an additional 6-month follow-up (n = 36). Data were analyzed from November 2018 to March 2019. <h3>Interventions</h3> The manualized CBT program aimed to recover functional internet use. The program consisted of 15 weekly group and up to 8 two-week individual sessions. <h3>Main Outcomes and Measures</h3> The predefined primary outcome was the Assessment of Internet and Computer Game Addiction Self-report (AICA-S). Secondary outcomes were self-reported internet addiction symptoms, time spent online on weekdays, psychosocial functioning, and depression. <h3>Results</h3> A total of 143 men (mean [SD] age, 26.2 [7.8] years) were analyzed based on intent-to-treat analyses. Of these participants, 50 of 72 men (69.4%) in the STICA group showed remission vs 17 of 71 men (23.9%) in the WLC group. In logistic regression analysis, remission in the STICA vs WLC group was higher (odds ratio, 10.10; 95% CI, 3.69-27.65), taking into account internet addiction baseline severity, comorbidity, treatment center, and age. Compared with the WLC groups, effect sizes at treatment termination of STICA were<i>d</i> = 1.19 for AICA-S,<i>d</i> = 0.88 for time spent online on weekdays,<i>d</i> = 0.64 for psychosocial functioning, and<i>d</i> = 0.67 for depression. Fourteen adverse events and 8 serious adverse events occurred. A causal relationship with treatment was considered likely in 2 AEs, one in each group. <h3>Conclusions and Relevance</h3> Short-term treatment for internet and computer game addiction is a promising, manualized, short-term CBT for a broad range of internet addictions in multiple treatment centers. Further trials investigating the long-term efficacy of STICA and addressing specific groups and subgroups compared with active control conditions are required. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01434589
Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries
Authors: Jin-Lin Hou, Wei Zhao, Changhyeong Lee, Hie-Won Hann, Cheng-Yuan Peng, Tawesak Tanwandee, Viacheslav Morozov, Hartwig Klinker, Jose D. Sollano, Adrian Streinu-Cercel, Hugo Cheinquer, Qing Xie, Yu-Ming Wang, Lai Wei, Ji-Dong Jia, Guozhong Gong, Kwang-Hyub Han, Wukui Cao, Mingliang Cheng, Xiaoping Tang, Deming Tan, Hong Ren, Zhongping Duan, Hong Tang, Zhiliang Gao, Shijun Chen, Shumei Lin, Jifang Sheng, Chengwei Chen, Jia Shang, Tao Han, Yanyan Ji, Junqi Niu, Jian Sun, Yongpeng Chen, Elizabeth L. Cooney, Seng-Gee Lim
Journal: Clinical Gastroenterology and Hepatology (2019)
Phase II study of de-intensification of radiation and chemotherapy for low-risk HPV-related oropharyngeal squamous cell carcinoma.
Authors: Bhishamjit S. Chera, Bahjat F. Qaqish, Mark C Weissler, David N. Hayes, Carol G. Shores, Alan Monroe, Roger F. Anderson, Justin Wu, Juneko E. Grilley-Olson, Jared Weiss, Trevor Hackman, Adam M Zanation, William M. Mendenhall, Robert J Amdur
Journal: Journal of Clinical Oncology (2013)

TPS6097 Background: The prognosis is excellent for low-risk human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC). Current standard chemoradiotherapy (CRT) regimens cure most patients but cause significant acute (mucositis) and long-term toxicities (xerostomia and dysphagia). Toxicity is primarily determined by the dose of radiotherapy and the intensity of chemotherapy. The aim of this study is to evaluate the pathological complete response (pCR) rate of low-risk HPV-associated OPSCC after de-intensified CRT. Methods: The major inclusion criteria are: 1) T0-T3, N0-N2c, M0, 2) HPV or p16 positive, and 3) &lt;/= 10 pack-years smoking history. Patients receive 60 Gy of intensity modulated radiotherapy (IMRT) with concurrent weekly intravenous cisplatinum (30 mg/m 2 ). CT scans are obtained 4 to 8 weeks after completion of CRT to assess response. All patients have a surgical resection of any clinically apparent residual primary tumor or biopsy of the primary site if there is no evidence of residual tumor and a selective neck dissection to encompass at least those nodal level(s) that were positive pre-treatment, within 4 to 14 weeks after CRT. Longitudinal assessments of quality of life (EORTC QLQ-C30 &amp; H&amp;N35, NDII), patient reported outcomes (PRO-CTCAE, EAT-10), and swallowing evaluations (modified barium swallow) are obtained prior to, during, and after CRT. The primary endpoint of this study is the rate of pCR after CRT. The null hypothesis is that the pCR rate for de-intensified CRT is at least 87%, the historical rate (based on the reported 3-year local regional control rate of 87% in the RTOG 0129). Power computations were performed for N=40, with a type I error of 14.2% if the true pCR rate is 0.87. The study will be done in 3 stages with 15+15+10 patients with interim analyses at 15 and 30 patients. The trial will be stopped if the pCR rate is &lt;/= 9/15 and 21/30. The null hypothesis will be accepted if the pCR rate is &gt;/= 33/40. Clinical trial information: NCT01530997.
Crosstalk between adipose tissue insulin resistance and liver macrophages in non-alcoholic fatty liver disease
Authors: Chiara Rosso, Konstantin Kazankov, Ramy Younes, Saeed Esmaili, Milena Marietti, Marco Sacco, Fabrizia Carli, Melania Gaggini, Federico Salomone, Holger Jon Møller, Maria Lorena Abate, Hendrik Vilstrup, Amalia Gastaldelli, Jacob George, Henning Grønbæk, Elisabetta Bugianesi
Journal: Journal of Hepatology (2019)
Basch Unbound—<i>The House of God</i> and Fiction as Resistance at 40
Authors: Stephen Bergman
Journal: JAMA (2019)

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Debio 1347 in patients with gastrointestinal cancers harboring an FGFR gene fusion: preliminary results
Authors: I. Matos, L. Goyal, J. Cleary, M. Voss, D. Oh, F. Meric Bernstam, C. Ng, G. Iyer, N. Ishii, Y. Hu, A. Vaslin Chessex, A. Pokorska-Bocci, V. Nicolas, Y. Kirpicheva, C. Zanna, K. Flaherty, J. Tabernero, D. Hyman
Journal: Annals of Oncology (2019)
Re: Agustina Bessa, Steven Maclennan, Deborah Enting, et al. Consensus in Bladder Cancer Research Priorities Between Patients and Healthcare Professionals Using a Four-stage Modified Delphi Method. Eur Urol 2019;76:260–1
Authors: Jon Mikel Inarritu, Daniele Castellani, Jeremy Y.C. Teoh
Journal: European Urology (2019)
Effect of short hairpin RNA targeting of fibroblast activation protein on tumor growth and angiogenesis in a 4T1 murine breast cancer model.
Authors: Fan Cai, Feng Peng, Chunting Wang, Zhiyong Li, Shuang Xian, Yuquan Wei
Journal: Journal of Clinical Oncology (2012)

e13538 Background: Fibroblast activation protein(FAP) is an increased abnormal signal protein in the TME and has both dipeptidyl peptidase and endopeptidase activity. FAP has been recognized to influence cancer growth and invasion, through its non- enzyme function or proteolytic activities in concert with other moleculars such as CD26, uPAR, β 1 -integrin, and MMP-1. Since FAP is over expression in epithelial cancers and absent from normal adult tissues, it has long been suggested to be a target of antitumor therapy. Methods: 21 BALB/C female mice implanted with 4T1 breast cancer were enrolled and randomly divided into three groups (n=7 per group) .The experiment group(E-group) was administered with shRNA targeting of FAP every 48 hours in 2 weeks by local administration, and the two control groups with HK or 5%GS. Tumor volumes and weights were monitored. Expression of FAP was detected by RT-PCR and immunohistochemistry staining. Collagen fiber, microvessel density and cell apoptosis were investigated. Results: The expression of FAP was reduced about 50% by shRNA targeting of FAP; the tumor volume and weight of the E-group showed significant reduction of 40% compared with the controls (p=0.001). Knockdown of FAP increased accumulation of disorganized collagen fibers; the MVD in control groups was about 4 times at least compared to the E-group (p&lt;0.001) and apoptosis cells markedly increased 3 fold (p=0.0015). Conclusions: Knockdown of FAP by shRNA interference mediated inhibition of breast cancer growth, amelioration of the tumor microenvironment including increased accumulation of disorganized collagen, suppressed angiogenesis, and promotion of apoptosis. FAP contributes to the formation of TME and is a stimulative factor of breast cancer growth. Target of FAP may be a potential supplemental therapeutic method for breast cancer.
Distinct genomic features in a retrospective cohort of mucosal, acral, and vulvovaginal melanomas
Authors: Katherine Shi, Bin Zhang, Betty Y. Kong, Yongzhan Zhang, Catherine Igartua, Lauren S. Mohan, Victor L. Quan, Elnaz Panah, Maria Cristina Isales, Nike Beaubier, Timothy J. Taxter, Kevin P. White, Lihua Zou, Pedram Gerami
Journal: Journal of the American Academy of Dermatology (2019)