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therapy resistance

Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Anna S Berghoff, Priscilla K Brastianos
Brain metastases (BMs) reflect an area of high clinical need, as up to 40% of patients with metastatic cancer will develop this morbid and highly fatal complication. Historically, treatment strategies have relied on local approaches including radiosurgery, whole-brain radiotherapy, and neurosurgical resection. Recently, targeted and immune-modulating therapies have shown promising responses and have been introduced in the clinical management of patients with BMs. Recent improvements in genomic technologies have enriched our understanding of BMs and have demonstrated that BMs present with significant genetic divergence from the originating primary tumor, such that potentially targetable genetic alterations are detected only in the BMs...
February 2018: Seminars in Neurology
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Amarateedha H Prak, Kristina M Dela Rosa
With skin lesions that have failed previous treatments, consideration for an atypical mycobacteria, specifically Mycobacterium marinum, infection should be suspected. Importance of the history cannot be stressed as this is a clue that the patient may have been inoculated and infected in the field environment. A marine with chronic right knee plaque for 3 yr that first appeared after a field exercise at The Basic School but worsened despite treatment with clindamycin, TMP-SMX, and incision and drainage in 2012...
March 14, 2018: Military Medicine
Barbara J Wilson, Laura J Zitella, Colleen H Erb, Jackie Foster, Mary Peterson, Sylvia K Wood
BACKGROUND: Cancer-related infections lead to increases in mortality, antibiotic use, and hospital stays. Other adverse outcomes include dose delays and reductions, which can result in suboptimal treatment outcomes. OBJECTIVES: Effective implementation of risk assessment and evidence-based interventions for the prevention and treatment of infection are essential to improve care and reduce costs related to infections in patients with cancer receiving immunosuppressive therapy...
April 1, 2018: Clinical Journal of Oncology Nursing
Michael K Krapf, Jennifer Gallus, Sahel Vahdati, Michael Wiese
Multidrug resistance occurring during cancer chemotherapy is a major obstacle for effectiveness and response to therapy and is often caused by ATP-binding cassette (ABC) efflux transporters. Belonging to the family of ABC transporters, breast cancer resistance protein is getting more and more in the spotlight of research. As a strategy to overcome multidrug resistance, inhibitors of ABC transporters were synthesized, which could be applied in combination with cytostatic drugs. For this purpose, 2,4-disubstituted pyridopyrimidine derivatives were synthesized...
March 16, 2018: Journal of Medicinal Chemistry
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
Jane Hawkey, David B Ascher, Louise M Judd, Ryan R Wick, Xenia Kostoulias, Heather Cleland, Denis W Spelman, Alex Padiglione, Anton Y Peleg, Kathryn E Holt
Acinetobacter baumannii is a common causative agent of hospital-acquired infections and a leading cause of infection in burns patients. Carbapenem-resistant A. baumannii is considered a major public-health threat and has been identified by the World Health Organization as the top priority organism requiring new antimicrobials. The most common mechanism for carbapenem resistance in A. baumannii is via horizontal acquisition of carbapenemase genes. In this study, we sampled 20 A. baumannii isolates from a patient with extensive burns, and characterized the evolution of carbapenem resistance over a 45 day period via Illumina and Oxford Nanopore sequencing...
March 16, 2018: Microbial Genomics
Jun Zhang, Xiaolong Qian, Fangfang Liu, Xiaojing Guo, Feng Gu, Li Fu
Objective: Tamoxifen is used as a complementary treatment for estrogen receptor (ER)-positive breast cancer (BCa), but many patients developed resistance. The aim of this study was to examine the role of syndecan-binding protein (SDCBP) silencing in ER-positive BCa cells. Methods: In MCF-7/T47D cells, the effects of SDCBP silence/overexpression on cell proliferation and estrogenic response were examined. Cell proliferation was examined using the MTT assay and cell cycle regulators were examined by Western blot...
February 2018: Cancer Biology & Medicine
Yangfeng Xiang, Jianqiang Zhao, Ming Zhao, Kejing Wang
Allicin has been reported to inhibit cancer cell proliferation, induce cell apoptosis and enhance the accumulation of reactive oxygen species. However, it has remained elusive whether allicin improves multidrug resistance in thyroid cancer cells through modulating autophagy. The present study demonstrated that combined use of allicin and cisplatin or carboplatin resulted in an enhanced growth inhibitory effect on SW1736 and HTh-7 cells. Furthermore, treatment with allicin significantly increased SW1736 and HTh-7 cell autophagy...
April 2018: Experimental and Therapeutic Medicine
Anas H Abu-Humaidan, Malin Elvén, Andreas Sonesson, Peter Garred, Ole E Sørensen
The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important in causing chronic and therapy resistant infections-is the intracellular persistence in non-immune cells. The objective of our study was to investigate whether persistent intracellular SA infection of epidermal keratinocytes resulted in complement activation...
2018: Frontiers in Immunology
Xiaowen Sun, Lei Deng, You Lu
Microvessels promote proliferation of tumor cells by delivering oxygen and nutrients, but rapid growth of tumors results in unmet demands for oxygen and nutrients, thereby creating a hypoxia microenvironment. Under hypoxic conditions, vascular endothelial cells (ECs) initiate the formation of immature and abnormal microvasculature. This results in leakage and tortuosity that facilitates tumor cell invasion, metastasis and resistance to cytotoxic treatment. Radiotherapy (RT) is a vital tumor treatment modality...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Barry H Smith, Lawrence S Gazda, Thomas J Fahey, Angelica Nazarian, Melissa A Laramore, Prithy Martis, Zoe P Andrada, Joanne Thomas, Tapan Parikh, Sudipta Sureshbabu, Nathaniel Berman, Allyson J Ocean, Richard D Hall, David J Wolf
Objective: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
IlKyoo Koh, Junghwa Cha, Junseong Park, Junjeong Choi, Seok-Gu Kang, Pilnam Kim
Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion...
March 15, 2018: Scientific Reports
William Pao, Chia-Huey Ooi, Fabian Birzele, Astrid Ruefli-Brasse, Michael A Cannarile, Bernhard Reis, Sebastian H Scharf, David A Schubert, Klas Hatje, Nadege Pelletier, Olivia Spleiss, John C Reed
Checkpoint inhibitor therapy has been a breakthrough in cancer research, but only some patients with cancer derive substantial benefit. Although mechanisms underlying sensitivity and resistance to checkpoint inhibitors are being elucidated, the importance of organ-specific regulation of immunity is currently underappreciated. Here, we call for a greater understanding of tissue-specific immunoregulation, namely, "tissue-specific immunostats," to make advances in treatments for cancer. A better understanding of how individual organs at baseline regulate the immune system could enable an improved precision medicine approach to cancer immunotherapy...
March 15, 2018: Cancer Discovery
Hannah Major-Monfried, Anne S Renteria, Attaphol Pawarode, Pavan Reddy, Francis Ayuk, Ernst Holler, Yvonne A Efebera, William J Hogan, Matthias Wölfl, Muna Qayed, Elizabeth O Hexner, Kitsada Wudhikarn, Rainer Ordemann, Rachel Young, Jay Shah, Matthew J Hartwell, Mohammed Chaudhry, Mina Aziz, Aaron Etra, Gregory A Yanik, Nicolaus Kröger, Daniela Weber, Yi-Bin Chen, Ryotaro Nakamura, Wolf Rösler, Carrie L Kitko, Andrew C Harris, Michael Pulsipher, Ran Reshef, Steven Kowalyk, George Morales, Ivan Torres, Umut Özbek, James L M Ferrara, John E Levine
Acute graft versus host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after one week of therapy often guides further treatment decisions, but long term outcomes vary widely between centers and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken after one week of systemic treatment for GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into test (n=236) and two validation cohorts separated in time (n = 142 and 129, respectively)...
March 15, 2018: Blood
María Paula Ceballos, Giulia Decándido, Ariel Darío Quiroga, Carla Gabriela Comanzo, Verónica Inés Livore, Florencia Lorenzetti, Flavia Lambertucci, Lorena Chazarreta-Cifre, Claudia Banchio, María de Luján Alvarez, Aldo Domingo Mottino, María Cristina Carrillo
Sirtuins (SIRTs) 1 and 2 deacetylases are overexpressed in hepatocellular carcinoma (HCC) and are associated with tumoral progression and multidrug resistance (MDR). In this study we analyzed whether SIRTs 1 and 2 activities blockage was able to affect cellular survival and migration and to modulate p53 and FoxO1 acetylation in HepG2 and Huh7 cells. Moreover, we analyzed ABC transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 3 (MRP3) expression. We used cambinol and EX-527 as SIRTs inhibitors...
March 12, 2018: Toxicology Letters
Beverley Greenwood-Van Meerveld, Ehsan Mohammadi, Rocco Latorre, Edward R Truitt, Gregory D Jay, Benjamin D Sullivan, Tannin A Schmidt, Nataliya Smith, Debra Saunders, Jadith Ziegler, Megan Lerner, Robert Hurst, Rheal A Towner
OBJECTIVE: To test in an animal model the hypothesis that rhPRG4 (lubricin), a highly O-glycosylated mucin-like glycoprotein, may be a novel surface-active therapeutic for treating bladder permeability with co-morbid bowel permeability. Previously we showed that inducing bladder permeability in rats with dilute protamine sulfate (PS) produced colonic permeability and visceral hypersensitivity, suggesting increased bladder permeability could represent an etiologic factor in both Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) and Irritable Bowel Syndrome (IBS)...
March 12, 2018: Urology
Brendan M Everett, Marc Y Donath, Aruna D Pradhan, Tom Thuren, Prem Pais, Jose C Nicolau, Robert J Glynn, Peter Libby, Paul M Ridker
BACKGROUND: Subclinical inflammation mediated in part by interleukin-1 beta (IL-1β) participates in peripheral insulin resistance and impaired pancreatic insulin secretion. OBJECTIVES: We tested the hypothesis that canakinumab, an IL-1β inhibitor, reduces incident diabetes. METHODS: The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) randomized 10,061 patients with prior MI and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L to placebo or canakinumab at doses of 50mg, 150mg, or 300mg subcutaneously once every three months...
March 3, 2018: Journal of the American College of Cardiology
Jun Hao, Xinpei Ci, Hui Xue, Rebecca Wu, Xin Dong, Stephen Yiu Chuen Choi, Haiqing He, Yu Wang, Fang Zhang, Sifeng Qu, Fan Zhang, Anne M Haegert, Peter W Gout, Amina Zoubeidi, Colin Collins, Martin E Gleave, Dong Lin, Yuzhuo Wang
BACKGROUND: Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. OBJECTIVE: To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. DESIGN, SETTING, AND PARTICIPANTS: Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers...
March 12, 2018: European Urology
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