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17:28 EDT 22nd October 2018 | BioPortfolio

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Showing "AACR 2018 Tumours drug resistance measured times faster" PubMed Articles 1–25 of 28,000+

Fighting Kinase Drug Resistance with Caspase Activators.

Kinase inhibitors are effective cancer therapies. Unfortunately, drug resistance emerges in response to kinase inhibition leading to loss of drug efficacy. In this issue of Cell Chemical Biology, Peh et al. (2018) demonstrate that caspase activators effectively delay onset of resistance to kinase inhibitors and are excellent co-therapeutics for a number of tumor types.

The Role of YKL-40 in Predicting Resistance to Docetaxel Chemotherapy in Prostate Cancer.

High baseline YKL-40 serum levels are associated with drug resistance in several solid tumours. However, their role in predicting docetaxel (DOC) resistance in prostate cancer (PCa) is unknown.

Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel.

Contemporary antiretroviral therapies (ART) and management strategies have diminished both human immunodeficiency virus (HIV) treatment failure and the acquired resistance to drugs in resource-rich regions, but transmission of drug-resistant viruses has not similarly decreased. In low- and middle-income regions, ART roll-out has improved outcomes, but has resulted in increasing acquired and transmitted resistances. Our objective was to review resistance to ART drugs and methods to detect it, and to provide ...

Within-host competition can delay evolution of drug resistance in malaria.

In the malaria parasite P. falciparum, drug resistance generally evolves first in low-transmission settings, such as Southeast Asia and South America. Resistance takes noticeably longer to appear in the high-transmission settings of sub-Saharan Africa, although it may spread rapidly thereafter. Here, we test the hypothesis that competitive suppression of drug-resistant parasites by drug-sensitive parasites may inhibit evolution of resistance in high-transmission settings, where mixed-strain infections are c...

Emergence and selection of isoniazid and rifampin resistance in tuberculosis granulomas.

Drug resistant tuberculosis is increasing world-wide. Resistance against isoniazid (INH), rifampicin (RIF), or both (multi-drug resistant TB, MDR-TB) is of particular concern, since INH and RIF form part of the standard regimen for TB disease. While it is known that suboptimal treatment can lead to resistance, it remains unclear how host immune responses and antibiotic dynamics within granulomas (sites of infection) affect emergence and selection of drug-resistant bacteria. We take a systems pharmacology ap...

Beating tumour drug resistance: "Lamarckian" induction in the spotlight.

Drug resistance is a major problem in cancer treatment. In cutaneous melanoma, a large fraction of tumours carry BRAF or BRAF mutations (hereinafter referred to as BRAF ), which result in activation of the mitogen-activated protein kinase (MAPK) pathway, sustaining cancer cell proliferation and survival. In 2011, a landmark phase III study demonstrated that vemurafenib, a drug specifically targeting cells with BRAF mutations, significantly improved progression-free survival over the conventional chemotherap...

Isobavachalcone sensitizes cells to E2-induced paclitaxel resistance by down-regulating CD44 expression in ER+ breast cancer cells.

Oestrogen receptor (ER) is expressed in approximately 60%-70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER-positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER-negative (ER-) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β-est...

Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort.

Transmission of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations, particularly that of minority drug-resistant variants, remains poorly understood. Population-based studies suggest that drug-resistant HIV-1 is less transmissible than drug-susceptible viruses. We compared HIV-1 drug-resistant genotypes among partner-pairs in order to assess the likelihood of transmission of drug resistance mutations and investigate the role of minority variants in HIV transmission.

Computational modelling of drug delivery to solid tumour: Understanding the interplay between chemotherapeutics and biological system for optimised delivery system.

Drug delivery to solid tumour involves multiple physiological, biochemical and biophysical processes taking place across a wide range of length and time scales. The therapeutic efficacy of anticancer drugs is influenced by the complex interplays among the intrinsic properties of tumours, biophysical aspects of drug transport and cellular uptake. Mathematical and computational modelling allows for a well-controlled study on the individual and combined effects of a wide range of parameters on drug transport a...

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

To estimate the prevalence of HIV drug resistance over time and identify risk factors for multi-class resistance.

Surveillance of Drug-Resistant Tuberculosis in Spain (2001-2015).

Multidrug-resistant tuberculosis (MDR-TB) is a cause of increasing concern. This study investigated first-line anti-TB drug resistance in Mycobacterium tuberculosis strains submitted to the Tuberculosis Reference Center in Córdoba (Spain) between 2001 and 2015. A total of 1,207 cultures were tested against first-line drugs using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 207 strains (17.2%), the greatest resistance being found in INH (5.3%) followed by streptomycin (3%), pyr...

Epidemiology of HIV drug resistance in HIV patients with virologic failure of first-line therapy in the country of Georgia.

HIV drug resistance is a major threat to sustained impact of antiretroviral therapy (ART). We studied epidemiology of drug resistance in the country of Georgia.

Structure and energy based quantitative missense variant effect analysis provides insights into drug resistance mechanisms of anaplastic lymphoma kinase mutations.

Anaplastic lymphoma kinase (ALK) is considered as a validated molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the effectiveness of molecularly targeted therapies using ALK inhibitors is almost universally limited by drug resistance. Drug resistance to molecularly targeted therapies has now become a major obstacle to effective cancer treatment and personalized medicine. It is of particular importance to provide an improved understanding on the mechanisms of res...

Drug resistance mechanisms and drug susceptibility testing for tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is the deadliest infectious disease and the associated global threat has worsened with the emergence of drug resistance, in particular multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Although the World Health Organization (WHO) End-TB Strategy advocates for universal access to antimicrobial susceptibility testing, this is not widely available and/or it is still underused. The majority of drug resistance in clinical MTB ...

Structural basis for drug resistance mechanisms against anaplastic lymphoma kinase.

Drug resistance to anaplastic lymphoma kinase (ALK) inhibitors (crizotinib and ceritinib) is caused by mutation in the region encoding kinase domain of ALK. Compounds with potential ability to inhibit all strains of ALK are a solution to tackle the problem of drug resistance. In this study, we delineated positions of residues possessing the ability to make ALK drug resistant upon mutation by assessing them using five parameters (conservation index, binding-site root-mean-square deviation, protein structure ...

Use of whole genome sequencing to predict Mycobacterium tuberculosis drug resistance in Indonesia.

Whole genome sequencing (WGS) is rarely used for drug-resistance testing of Mycobacterium tuberculosis in high-endemic settings. We present the first study from Indonesia, which has the second highest tuberculosis (TB) burden worldwide, with less than 50% of drug-resistant cases currently detected.

The PDR-type ABC transporters AtrA and AtrG are involved in azole drug resistance in Aspergillus oryzae.

For strain improvement of Aspergillus oryzae, development of the transformation system is essential, wherein dominant selectable markers, including drug-resistant genes, are available. However, A. oryzae generally has a relatively high resistance to many antifungal drugs effective against yeasts and other filamentous fungi. In the course of the study, while investigating azole drug resistance in A. oryzae, we isolated a spontaneous mutant that exhibited high resistance to azole fungicides and found that ple...

Modalities to monitor the treatment response in tuberculosis.

Considering the global epidemic of drug resistance in Mycobacterium tuberculosis, early and accurate diagnosis as well as prompt initiation of antitubercular therapy (ATT) forms the mainstay of tuberculosis control programs. Patients on ATT may develop treatment failure due to diverse reasons including emergence of drug resistance in the host during the course of therapy. Monitoring the timely response to treatment in such cases has a significant role in rapid identification of drug resistant strains and in...

Establishment of 2D cell cultures derived from 3D MCF-7 spheroids displaying a Doxorubicin resistant profile.

In vitro 3D cancer spheroids generally exhibit a drug resistance profile similar to that found in solid tumors. Due to this property, these models are an appealing for anticancer compounds screening. Nevertheless, the techniques and methods aimed for drug discovery are mostly standardized for cells cultured in 2D. The development of 2D cell culture models displaying a drug resistant profile is required to mimic the in vivo tumors, while the equipment, techniques and methodologies established for conventiona...

Clinical and Drug Resistance Characteristics of New Pediatric Tuberculosis Cases in Northern China.

The aim of this study was to evaluate the clinical features and characteristics of drug resistance in newly diagnosed pediatric tuberculosis (TB) patients in northern China.

Vascularization of the Tumours Affects the Pharmacokinetics of Bleomycin and the Effectiveness of Electrochemotherapy.

Pre-clinical and clinical data indicate differences in the responses of melanoma and carcinoma tumours to electrochemotherapy. The purpose of this study was to investigate the origin of this difference, whether it is due to the intrinsic difference in tumour cell susceptibility to the chemotherapeutic, or due to the tumour microenvironment. For this purpose, we performed a pre-clinical study in B16F1 melanoma and TS/A carcinoma tumours in mice, in which the anti-tumour effectiveness of electrochemotherapy w...

pH sensitive liposomes delivering tariquidar and doxorubicin to overcome multidrug resistance of resistant ovarian cancer cells.

Multidrug resistance of tumour cells is one of the most important hurdles in tumour chemotherapy. To overcome the multidrug resistance, we constructed a pH-sensitive liposome formulation (pHSL) by loading tariquidar (TQR) and DOX simultaneously in this work. The formulation showed high stability at pH 7.4 and excellent sensitivity at acidic pH, which facilitated the delivery of TQR and DOX into cells. Cellular experiments demonstrated that the pHSL/TQR/DOX 0.05 could almost restore the drug sensitivity of O...

HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique.

Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care.

Characterization of HIV-1 subtypes and transmitted drug resistance among treatment-naive HIV-infected individuals in Zhejiang, China, 2014-2017.

In recent years, transmitted drug resistance (TDR) has adversely impacted upon first-line therapy for HIV-infected individuals. To understand the current subtype distribution and TDR level in Zhejiang, China we performed phylogenetic analysis and genotypic drug resistance testing of treatment-naive HIV-infected individuals. A total of 153 HIV-1 Pol genes were successfully amplified. The distribution of HIV-1 genotypes was as follows: CRF01_AE (43.8%); CRF07_BC (37.9%); subtype B/B' (7.2%); CRF08_BC (5.2%); ...

Whole genome sequencing and single nucleotide polymorphisms in multi-drug resistant clinical isolates of Mycobacterium tuberculosis from the Philippines.

Thousands of cases of multi-drug resistant Mycobacteria tuberculosis (MTB) have been observed in the Philippines but studies on the genotypes that underlie the observed drug resistance profiles have been lacking. This study aimed to analyse whole genomes of clinical isolates of MTB representing varying resistance profiles to identify single nucleotide polymorphisms (SNPs) in resistance-associated genes.

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