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https://www.readbyqxmd.com/read/29872576/potential-immune-priming-of-the-tumor-microenvironment-with-folfox-chemotherapy-in-locally-advanced-rectal-cancer
#1
Campbell S Roxburgh, Jinru Shia, Efsevia Vakiani, Tanisha Daniel, Martin R Weiser
Strategies to enhance tumor immunogenicity may expand the role of immunotherapy beyond the mismatch repair-deficient subtype. In this pilot study, biopsies were performed at baseline and after four cycles of FOLFOX in eight patients receiving neoadjuvant chemotherapy for stage II/III locally advanced rectal cancer. Immunostaining was performed for T cell subsets (CD3+, CD8+, CD45RO+); macrophages (CD163+); T regulatory cells (FOXP3+); and expression of MHC class I, PD-1 and PD-L1. Changes in cell number or intensity were quantified and correlated with treatment response...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29799651/auroramycin-a-potent-antibiotic-from-streptomyces-roseosporus-by-crispr-cas9-activation
#2
Huimin Zhao, Yee Hwee Lim, Fong Tian Wong, Wan Lin Yeo, Kuan Chieh Ching, Yi Wee Lim, Elena Heng, Shuwen Chen, De-Juin Tsai, Tsai-Ling Lauderdale, Kak-Shan Shia, Ying Swan Ho, Shawn Hoon, Ee Lui Ang, Mingzi M Zhang
Silent biosynthetic gene clusters represent a potentially rich source for new bioactive compounds. We report the discovery, characterization and biosynthesis of a novel doubly glycosylated 24-membered polyene macrolactam from a silent biosynthetic gene cluster in Streptomyces roseosporus using the CRISPR-Cas9 gene cluster activation strategy. Structural characterization of this polyketide, named auroramycin, revealed a rare isobutyrylmalonyl extender unit and a unique pair of aminosugars. Relative and absolute stereochemistry were determined using a combination of spectroscopic analyses, chemical derivatization, and computational analysis...
May 25, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29785848/the-total-synthesis-of-tetarimycin-a-%C3%A2-naphthacemycin-a-9-and-%C3%A2-fasamycin-a-structure-activity-relationship-studies-against-drug-resistant-bacteria
#3
Jing-Kai Huang, Tsai-Ling Yang Lauderdale, Chun-Cheng Lin, Kak-Shan Shia
Making use of a reductive olefin coupling reaction and Michael-Dieckmann condensation as two key operations, we have completed a concise total synthesis of tetarimycin A, (±)-naphthacemycin A9 and (±)-fasamycin A in a highly convergent and practical protocol. Synthetic procedures thus developed have also been applied to providing related analogues for structure-activity relationship studies, thereof coming to a conclusion that the free hydroxyl group at C-10 is essential for exerting inhibitory activities against a panel of Gram-positive bacteria, including drug-resistant strains VRE and MRSA...
May 22, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29774265/assisted-reproduction-and-middle-east-kinship-a-regional-and-religious-comparison
#4
Marcia C Inhorn, Daphna Birenbaum-Carmeli, Soraya Tremayne, Zeynep B Gürtin
This article compares the use of assisted reproductive technology (ART) and resultant kinship formations in four Middle Eastern settings: the Sunni Muslim Arab world, the Sunni Muslim but officially 'secular' country of Turkey, Shia Muslim Iran and Jewish Israel. This four-way comparison reveals considerable similarities, as well as stark differences, in matters of Middle Eastern kinship and assisted reproduction. The permissions and restrictions on ART, often determined by religious decrees, may lead to counter-intuitive outcomes, many of which defy prevailing stereotypes about which parts of the Middle East are more 'progressive' or 'conservative'...
June 2017: Reproductive Biomedicine & Society Online
https://www.readbyqxmd.com/read/29661050/healthcare-resource-use-and-costs-associated-with-chronic-kidney-disease-in-us-private-insurance-patients-with-multiple-myeloma
#5
Debajyoti Bhowmik, Xue Song, Michele Intorcia, Shia T Kent, Nianwen Shi
Objectives Within a median 1.2 years after patients have an initial diagnosis with multiple myeloma, up to 61% were diagnosed with renal impairment and 50% were diagnosed with chronic kidney disease. This study estimated economic burden associated with chronic kidney disease in multiple myeloma patients in the US. Methods In this retrospective cohort study, patients ≥18 years old with ≥1 inpatient or ≥ 2 outpatient multiple myeloma diagnoses between 1 January 2008 and 31 March 2015 were identified from MarketScan® Commercial and Medicare Supplemental Databases...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29624511/poorly-differentiated-clusters-predict-colon-cancer-recurrence-an-in-depth-comparative-analysis-of-invasive-front-prognostic-markers
#6
Tsuyoshi Konishi, Yoshifumi Shimada, Lik Hang Lee, Marcela S Cavalcanti, Meier Hsu, Jesse Joshua Smith, Garrett M Nash, Larissa K Temple, José G Guillem, Philip B Paty, Julio Garcia-Aguilar, Efsevia Vakiani, Mithat Gonen, Jinru Shia, Martin R Weiser
This study aimed to compare common histologic markers at the invasive front of colon adenocarcinoma in terms of prognostic accuracy and interobserver agreement. Consecutive patients who underwent curative resection for stages I to III colon adenocarcinoma at a single institution in 2007 to 2014 were identified. Poorly differentiated clusters (PDCs), tumor budding, perineural invasion, desmoplastic reaction, and Crohn-like lymphoid reaction at the invasive front, as well as the World Health Organization (WHO) grade of the entire tumor, were analyzed...
June 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29571600/stability-basin-estimates-fall-risk-from-observed-kinematics-demonstrated-on-the-sit-to-stand-task
#7
Victor Shia, Talia Yuki Moore, Patrick Holmes, Ruzena Bajcsy, Ram Vasudevan
The ability to quantitatively measure stability is essential to ensuring the safety of locomoting systems. While the response to perturbation directly reflects the stability of a motion, this experimental method puts human subjects at risk. Unfortunately, existing indirect methods for estimating stability from unperturbed motion have been shown to have limited predictive power. This paper leverages recent advances in dynamical systems theory to accurately estimate the stability of human motion without requiring perturbation...
April 27, 2018: Journal of Biomechanics
https://www.readbyqxmd.com/read/29566109/adoption-of-total-neoadjuvant-therapy-for-locally-advanced-rectal-cancer
#8
Andrea Cercek, Campbell S D Roxburgh, Paul Strombom, J Joshua Smith, Larissa K F Temple, Garrett M Nash, Jose G Guillem, Philip B Paty, Rona Yaeger, Zsofia K Stadler, Kenneth Seier, Mithat Gonen, Neil H Segal, Diane L Reidy, Anna Varghese, Jinru Shia, Efsevia Vakiani, Abraham J Wu, Christopher H Crane, Marc J Gollub, Julio Garcia-Aguilar, Leonard B Saltz, Martin R Weiser
Importance: Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. Objective: To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC...
June 14, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29540710/an-epidemiological-human-disease-network-derived-from-disease-co-occurrence-in-taiwan
#9
Yefei Jiang, Shuangge Ma, Ben-Chang Shia, Tian-Shyug Lee
In "classic" biomedical research, diseases have usually been studied individually. The pioneering human disease network (HDN) studies jointly consider a large number of diseases, analyse their interconnections, and provide a more comprehensive description of diseases. However, most of the existing HDN studies are based on molecular information and can only partially describe disease interconnections. Building on the unique Taiwan National Health Insurance Research Database (NHIRD), in this study, we construct the epidemiological HDN (eHDN), where two diseases are concluded as interconnected if their observed probability of co-occurrence deviating that expected under independence...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29490779/the-effects-of-religious-and-cultural-beliefs-on-muslim-transplant-candidates-during-the-pretransplant-waiting-period
#10
Zahra Sheikhalipour, Vahid Zamanzadeh, Leili Borimnejad, Leila Valizadeh, Sarah Newton, Mohammad Shahbazi, Afshar Zomorrodi, Mojtaba Nazari
BACKGROUND: Awaiting organ transplantation can be stressful, and pretransplant candidates' religious and cultural beliefs can influence how they adapt to the stress. While little is known about the effect religious and cultural beliefs have on the pretransplant waiting period, virtually nothing is known regarding whether and how Shia Muslim patients' religious and cultural beliefs facilitate more positive patient outcomes while they await transplantation. Therefore, it is important for nurses and other health care providers to understand transplant candidates' experiences dealing with the stressors that present themselves during the pretransplant waiting period, especially how their religious and cultural beliefs affect their adaptation to the stressors...
February 1, 2018: Research and Theory for Nursing Practice
https://www.readbyqxmd.com/read/29484140/a-taiwanese-population-based-study-on-the-association-between-chronic-tonsillitis-and-tonsil-cancer
#11
Shih-Han Hung, Li-Ting Kao, Chung-Chien Huang, Ben-Chang Shia, Herng-Ching Lin
Although it is known that inflammatory processes elevate the risk of cancer, to date the association between chronic tonsillitis and tonsil cancer remains unknown. This study aimed to evaluate the association of chronic tonsillitis with tonsil cancer based on a population-based database in Taiwan. We retrieved data for this study from the Longitudinal Health Insurance Database 2005. This case-control study included 489 patients with tonsil cancer and 2445 matched controls. We used conditional logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for having been previously diagnosed with chronic tonsillitis between patients with tonsil cancer and the controls...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29484137/alzheimer-s-disease-is-associated-with-prostate-cancer-a-population-based-study
#12
Herng-Ching Lin, Li-Ting Kao, Shiu-Dong Chung, Chung-Chien Huang, Ben-Chang Shia, Chao-Yuan Huang
Alzheimer's disease and cancer are increasingly prevalent with advancing age. However, the association between Alzheimer's disease and prostate cancer remains unclear. The aim of this study was to examine the relationship between prior Alzheimer's disease and subsequent prostate cancer using a population-based dataset in Taiwan. Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2005. This case-control study included 2101 prostate cancer patients as cases and 6303 matched controls...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29451951/time-course-and-clinical-characterization-of-cisplatin-induced-ototoxicity-after-treatment-for-nasopharyngeal-carcinoma-in-a-south-east-asian-population
#13
Sze Ling Chan, Li Shia Ng, Xueying Goh, Chor Hiang Siow, Han Lee Goh, Boon Cher Goh, Timothy Cheo, Kwok Seng Loh, Liam R Brunham
BACKGROUND: The purpose of this study was to characterize the clinical course of hearing loss in patients with nasopharyngeal carcinoma (NPC) and the clinical factors affecting its severity. METHODS: The time course of hearing loss in patients with NPC was assessed using threshold shift from baseline and Common Terminology Criteria for Adverse Events (CTCAE) grade. RESULTS: In the chemoradiotherapy (CRT) groups, the threshold shift was significantly higher from 3 months at 4 kHz (P = 2...
February 16, 2018: Head & Neck
https://www.readbyqxmd.com/read/29447164/modern-sunni-shia-conflicts-and-their-neglected-tropical-diseases
#14
EDITORIAL
Peter J Hotez
No abstract text is available yet for this article.
February 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29444439/differential-effector-engagement-by-oncogenic-kras
#15
Tina L Yuan, Arnaud Amzallag, Rachel Bagni, Ming Yi, Shervin Afghani, William Burgan, Nicole Fer, Leslie A Strathern, Katie Powell, Brian Smith, Andrew M Waters, David Drubin, Ty Thomson, Rosy Liao, Patricia Greninger, Giovanna T Stein, Ellen Murchie, Eliane Cortez, Regina K Egan, Lauren Procter, Matthew Bess, Kwong Tai Cheng, Chih-Shia Lee, Liam Changwoo Lee, Christof Fellmann, Robert Stephens, Ji Luo, Scott W Lowe, Cyril H Benes, Frank McCormick
KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29438172/gastric-carcinomas-with-lymphoid-stroma-an-evaluation-of-the-histopathologic-and-molecular-features
#16
Erika Hissong, Girish Ramrattan, Pan Zhang, Xi Kathy Zhou, Gloria Young, David S Klimstra, Jinru Shia, Helen Fernandes, Rhonda K Yantiss
Gastric carcinoma with lymphoid stroma is an uncommon variant enriched for mutually exclusive Epstein-Barr virus (EBV) positivity and mismatch repair (MMR) deficiency. We performed this study to evaluate molecular alterations in this morphologically homogeneous subtype and compare them with 295 conventional gastric cancers analyzed in The Cancer Genome Atlas study. We identified 31 study cases and subjected them to in situ hybridization for EBV-encoded RNAs and assessment for MMR status. Immunostains for PD-L1, β-catenin, and HER2 were performed; extracted DNA was sequenced with a Comprehensive Cancer Panel...
April 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29409152/is-rheumatoid-arthritis-a-cardiovascular-risk-equivalent-to-diabetes
#17
Jeffrey R Curtis, Shuo Yang, Jasvinder A Singh, Fenglong Xie, Lang Chen, Huifeng Yun, Paul Muntner, Shia T Kent, Emily B Levitan, Monika M Safford, Kenneth G Saag, Jie Zhang
BACKGROUND/PURPOSE: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines recommend statins for patients with diabetes aged 40-75 years due to their elevated cardiovascular disease (CVD) risk. We compared the incidence of hospitalized acute myocardial infarction (MI), stroke, and coronary revascularization according to whether patients had diabetes, rheumatoid arthritis (RA), both or neither. METHODS: Using 2006 to 2010 private and public health plan claims, we identified 4 mutually exclusive retrospective cohorts age>40: patients with 1) RA and diabetes; 2) RA only; 3) diabetes only; 4) neither condition...
February 6, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29367431/evaluating-mismatch-repair-deficiency-in-pancreatic-adenocarcinoma-challenges-and-recommendations
#18
Zishuo I Hu, Jinru Shia, Zsofia K Stadler, Anna M Varghese, Marinela Capanu, Erin Salo-Mullen, Maeve A Lowery, Luis A Diaz, Diana Mandelker, Kenneth H Yu, Alice Zervoudakis, David P Kelsen, Christine A Iacobuzio-Donahue, David S Klimstra, Leonard B Saltz, Ibrahim H Sahin, Eileen M O'Reilly
Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in mismatch repair deficient (MMR-D) solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D pancreatic ductal adenocarcinoma (PDAC) and assess the utility of next-generation sequencing (NGS) in providing additional prognostic and predictive information for MMR-D PDAC...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29316426/clinical-sequencing-defines-the-genomic-landscape-of-metastatic-colorectal-cancer
#19
Rona Yaeger, Walid K Chatila, Marla D Lipsyc, Jaclyn F Hechtman, Andrea Cercek, Francisco Sanchez-Vega, Gowtham Jayakumaran, Sumit Middha, Ahmet Zehir, Mark T A Donoghue, Daoqi You, Agnes Viale, Nancy Kemeny, Neil H Segal, Zsofia K Stadler, Anna M Varghese, Ritika Kundra, Jianjiong Gao, Aijazuddin Syed, David M Hyman, Efsevia Vakiani, Neal Rosen, Barry S Taylor, Marc Ladanyi, Michael F Berger, David B Solit, Jinru Shia, Leonard Saltz, Nikolaus Schultz
Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1,134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared with left-sided primaries...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29314840/development-of-stem-cell-mobilizing-agents-targeting-cxcr4-receptor-for-peripheral-blood-stem-cell-transplantation-and-beyond
#20
Chien-Huang Wu, Jen-Shin Song, Hsuan-Hao Kuan, Szu-Huei Wu, Ming-Chen Chou, Jiing-Jyh Jan, Lun K Tsou, Yi-Yu Ke, Chiung-Tong Chen, Kai-Chia Yeh, Sing-Yi Wang, Teng-Kuang Yeh, Chen-Tso Tseng, Chen-Lung Huang, Mine-Hsine Wu, Po-Chu Kuo, Chia-Jui Lee, Kak-Shan Shia
The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., 16) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug 1 (AMD3100), and thus considered a potential drug candidate for PBSCT indication...
February 8, 2018: Journal of Medicinal Chemistry
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