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Treatment resistant

Nilamadhab Kar, Socorro Barreto, Rahul Chandavarkar
Clozapine is effective in treatment resistant schizophrenia; however, it is underutilised probably because of its side effects. The side effects are also the potential reasons for clozapine discontinuation. A mandatory requirement for its use is regular monitoring of white blood cell count and absolute neutrophil count. However there are many side effects that need monitoring in clinical practice considering their seriousness. This article tries to summarise the clinical concerns surrounding the serious side effects of clozapine some of which are associated with fatalities and presents a comprehensive way to monitor patients on clozapine in clinical practice...
November 30, 2016: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Sinead Toomey, Stephen F Madden, Simon J Furney, Yue Fan, Mark McCormack, Carragh Stapleton, Mattia Cremona, Gianpiero L Cavalleri, Malgorzata Milewska, Naomi Elster, Aoife Carr, Joanna Fay, Elaine W Kay, Susan Kennedy, John Crown, William M Gallagher, Bryan T Hennessy, Alex J Eustace
BACKGROUND: Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. RESULTS: We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients...
October 20, 2016: Oncotarget
Lixia Yuan, Min Liu, Guiqin Liu, Dacheng Li, Zhengping Wang, Bingquan Wang, Jun Han, Min Zhang
Combination therapy with more than one therapeutic agent can improve therapeutic efficiency and decrease drug resistance. In this study, the interactions of human serum albumin (HSA) with individual or combined anticancer drugs, (-)-epigallocatechin-3-gallate (EGCG) and 5-fluorouracil (FU), were investigated by fluorescence and circular dichroism (CD) spectroscopy. The results demonstrated that the interaction of EGCG or FU with HSA is a process of static quenching and EGCG formed a more stable complex. The competitive experiments of site markers suggested that both anti-carcinogens mainly bound to site I (subdomain IIA)...
October 18, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Money Gupta, Rashi Chauhan, Yamuna Prasad, Gulshan Wadhwa, Chakresh Kumar Jain
The lack of complete treatments and appearance of multiple drug-resistance strains of Burkholderia cepacia complex (Bcc) are causing an increased risk of lung infections in cystic fibrosis patients. Bcc infection is a big risk to human health and demands an urgent need to identify new therapeutics against these bacteria. Network biology has emerged as one of the prospective hope in identifying novel drug targets and hits. We have applied protein-protein interaction methodology to identify new drug-target candidates (orthologs) in Burkhloderia cepacia GG4, which is an important strain for studying the quorum-sensing phenomena...
October 8, 2016: Computational Biology and Chemistry
Jun Itakura, Masayuki Kurosaki, Chitomi Hasebe, Yukio Osaki, Kouji Joko, Hitoshi Yagisawa, Shinya Sakita, Hiroaki Okushin, Takashi Satou, Hiroyuki Hisai, Takehiko Abe, Keiji Tsuji, Takashi Tamada, Haruhiko Kobashi, Akeri Mitsuda, Yasushi Ide, Chikara Ogawa, Syotaro Tsuruta, Kouichi Takaguchi, Miyako Murakawa, Yasuhiro Asahina, Nobuyuki Enomoto, Namiki Izumi
BACKGROUNDS & AIMS: We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. METHODS: This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment...
2016: PloS One
Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Ofer Nathan Gofrit, Stephen Frank, Amichay Meirovitz, Hovav Nechushtan, Marina Orevi
AIM: Castrate-resistant prostate cancer (CRPC) often shows histological evidence of neuroendocrine differentiation (NED). To evaluate the extent of NED in patients with CRPC, we used PET/CT with Ga-[DOTA-Tyr]-octreotate (Ga-DOTA-TATE), a somatostatin analog that binds somatostatin receptor 2 with high affinity. This radiotracer is used in imaging of neuroendocrine tumors. METHODS: Twelve patients (mean age, 65 [SD, 12] years) with CRPC were studied. Their mean prostate-specific antigen level at scanning was 85...
October 21, 2016: Clinical Nuclear Medicine
Wei-Lin Jin, Xiao-Yuan Mao, Guan-Zhong Qiu
Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor-suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin-proteasome system is a well-orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways...
October 24, 2016: Medicinal Research Reviews
Peter M Fischer
Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation...
October 24, 2016: Medicinal Research Reviews
Laura Campbell-Sills, Peter P Roy-Byrne, Michelle G Craske, Alexander Bystritsky, Greer Sullivan, Murray B Stein
BACKGROUND: Many patients with anxiety disorders remain symptomatic after receiving evidence-based treatment, yet research on treatment-resistant anxiety is limited. We evaluated effects of cognitive behavioral therapy (CBT) on outcomes of patients with medication-resistant anxiety disorders using data from the Coordinated Anxiety Learning and Management (CALM) trial. METHODS: Primary care patients who met study entry criteria (including DSM-IV diagnosis of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or social anxiety disorder) despite ongoing pharmacotherapy of appropriate type, dose, and duration were classified as medication resistant (n = 227)...
October 24, 2016: Depression and Anxiety
Nina Kimer, Julie Steen Pedersen, Troels Malte Busk, Lise Lotte Gluud, Lise Hobolth, Aleksander Krag, Søren Møller, Flemming Bendtsen
BACKGROUND AND RATIONALE: Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial investigates the effects of rifaximin on hemodynamics, renal function and vasoactive hormones. METHODS: We randomized 54 stable out-patients with cirrhosis and ascites to rifaximin 550 mg BD (n=36) or placebo BD (n=18)...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Mary Jc Hendrix, Irawati Kandela, Andrew P Mazar, Elisabeth A Seftor, Richard Eb Seftor, Naira V Margaryan, Luigi Strizzi, George F Murphy, Georgina V Long, Richard A Scolyer
Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. It is the leading cause of skin cancer deaths with a median overall survival for advanced-stage metastatic disease of <6 months. Despite advances in the field with conventional and targeted therapies, the heterogeneity of melanoma poses the greatest ongoing challenge, ultimately leading to relapse and progression to a more drug-resistant tumor in most patients. Particularly noteworthy are recent findings, indicating that these therapies exert selective pressure on tumors resulting in the activation of pathways associated with cancer stem cells that are unresponsive to current therapy...
October 24, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Vera Pader, Sanika Hakim, Kimberley L Painter, Sivaramesh Wigneshweraraj, Thomas B Clarke, Andrew M Edwards
Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA)(1,2). Although resistance is rare, treatment failure can occur in more than 20% of cases(3,4) and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S...
October 24, 2016: Nature Microbiology
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
Ifedayo Victor Ogungbe, William N Setzer
Malaria, leishmaniasis, Chagas disease, and human African trypanosomiasis continue to cause considerable suffering and death in developing countries. Current treatment options for these parasitic protozoal diseases generally have severe side effects, may be ineffective or unavailable, and resistance is emerging. There is a constant need to discover new chemotherapeutic agents for these parasitic infections, and natural products continue to serve as a potential source. This review presents molecular docking studies of potential phytochemicals that target key protein targets in Leishmania spp...
October 19, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shiho Fujisaka, Siegfried Ussar, Clary Clish, Suzanne Devkota, Jonathan M Dreyfuss, Masaji Sakaguchi, Marion Soto, Masahiro Konishi, Samir Softic, Emrah Altindis, Ning Li, Georg Gerber, Lynn Bry, C Ronald Kahn
Interactions of diet, gut microbiota, and host genetics play important roles in the development of obesity and insulin resistance. Here, we have investigated the molecular links between gut microbiota, insulin resistance, and glucose metabolism in 3 inbred mouse strains with differing susceptibilities to metabolic syndrome using diet and antibiotic treatment. Antibiotic treatment altered intestinal microbiota, decreased tissue inflammation, improved insulin signaling in basal and stimulated states, and improved glucose metabolism in obesity- and diabetes-prone C57BL/6J mice on a high-fat diet (HFD)...
October 24, 2016: Journal of Clinical Investigation
Jessica M Andriolo, Richard J Rossi, Casey A McConnell, Baili I Connors, Kevin Trout, M K Hailer, Marisa L Pedulla, Jack L Skinner
The Centers for Disease Control and Prevention have estimated that each year, two million people in the United States become infected with antibiotic-resistant bacteria, of which, approximately 23 000 die as a direct result of these infections. Phage therapy, or the treatment of bacterial infection by specific, antagonistic viruses, provides one alternative to traditional antibiotics. Bacteriophages, or phages, are bacteriaspecific viruses that possess biological traits that allow for not only the removal of bacterial infection, but also the evasion of bacterial resistance which renders antibiotics ineffective...
October 19, 2016: IEEE Transactions on Nanobioscience
Christen Ravn, Ulrika Furustrand Tafin, Bertrand Bétrisey, Søren Overgaard, Andrej Trampuz
Background and purpose - Antibiotic treatment of patients before specimen collection reduces the ability to detect organisms by culture. We investigated the suppressive effect of antibiotics on the growth of non-adherent, planktonic, and surface-related biofilm bacteria in vitro by using sonication and microcalorimetry methods. Patients and methods - Biofilms of Staphylococcus aureus, S. epidermidis, Escherichia coli, and Propionibacterium acnes were formed on porous glass beads and exposed for 24 h to antibiotic concentrations from 1 to 1,024 times the minimal inhibitory concentration (MIC) of vancomycin, daptomycin, rifampin, flucloxacillin, or ciprofloxacin...
October 24, 2016: Acta Orthopaedica
Marius Schwerg, Anna Slagman, Karl Stangl, Verena Stangl
BACKGROUND: Renal denervation is used as a treatment option for patients with resistant hypertension. But only a subgroup of patients benefits from RDN. Biomarkers might be helpful to identify patients who respond to RDN. Copeptin as a surrogate for vasopressin levels is increased in hypertension and other cardiovascular diseases. This study aims to evaluate the effect of RDN on Copeptin and its prognostic value for response to RDN. METHOD AND RESULTS: A total of 40 patients have been included in the study...
October 24, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
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