Search results for "COMBINATION"
showing 10 items of 1379 documents
Management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.
2019
Introduction: Infections are among the most frequent complications in patients with hematological and oncological diseases. They might be classified as fever of unknown origin and microbiologically or clinically documented infections. Optimal duration of antimicrobial treatment is still unclear in these patients.Areas covered: We provide an overview on the management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.Expert opinion: Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam. Several clinical studies support the assumption that the primary antibiotic regime…
Mitochondrial introgression suggests extensive ancestral hybridization events among Saccharomyces species.
2017
Horizontal gene transfer (HGT) in eukaryotic plastids and mitochondrial genomes is common, and plays an important role in organism evolution. In yeasts, recent mitochondrial HGT has been suggested between S. cerevisiae and S. paradoxus. However, few strains have been explored given the lack of accurate mitochondrial genome annotations. Mitochondrial genome sequences are important to understand how frequent these introgressions occur, and their role in cytonuclear incompatibilities and fitness. Indeed, most of the Bateson-Dobzhansky-Muller genetic incompatibilities described in yeasts are driven by cytonuclear incompatibilities. We herein explored the mitochondrial inheritance of several wor…
Mechanisms of viral mutation
2016
The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be intro…
Inherited variants in XRCC2 and the risk of breast cancer
2019
Background XRCC2 participates in homologous recombination and in DNA repair. XRCC2 has been reported to be a breast cancer susceptibility gene and is now included in several breast cancer susceptibility gene panels. Methods We sequenced XRCC2 in 617 Polish women with familial breast cancer and found a founder mutation. We then genotyped 12,617 women with breast cancer and 4599 controls for the XRCC2 founder mutation. Results We identified a recurrent truncating mutation of XRCC2 (c.96delT, p.Phe32fs) in 3 of 617 patients with familial breast cancer who were sequenced. The c.96delT mutation was then detected in 29 of 12,617 unselected breast cancer cases (0.23%) compared to 11 of 4599 cancer…
Final results of the McCAVE trial: A double-blind, randomized phase 2 study of vanucizumab (VAN) plus FOLFOX vs. bevacizumab (BEV) plus FOLFOX in pat…
2017
3539 Background: VEGF-A and ANG-2 have complementary roles in regulation of tumor angiogenesis. Targeting VEGF-A with BEV in combination chemotherapy (CT) in mCRC has proven to increase PFS and OS. ANG-2 is overexpressed and associated with poor outcome of mCRC pts receiving BEVcontaining treatment. Hence, dual blockade of VEGF-A and ANG-2 by the bispecific mAb VAN with standard CT may improve clinical activity in mCRC. Methods: All pts received mFOLFOX-6 and were randomized 1:1 to also receive intravenous VAN 2000 mg every other week (Q2W) (Arm A) or BEV 5 mg/kg Q2W (Arm B). The primary end point was investigator assessed progression-free survival (PFS). Key eligibility criteria included …
The Current Landscape of Clinical Trials for Systemic Treatment of HCC
2021
Simple Summary Liver cancer is a life-threatening disease. Apart from surgery and catheter-guided therapies, drugs are a central pillar for its treatment. Clinical trials are research studies that are designed to evaluate the treatment effect of a given drug. Therefore, they are the driving force behind innovation and medical progress. One such innovation in the past years has been immunotherapy, which has become increasingly important for treating cancer. Recently, the first such therapy has been approved for the treatment of liver cancer. Current clinical trials are exploring the benefit of immunotherapy and other therapies for this disease. This article gives an overview of such trials p…
“Open Sesame?”: biomarker status of the human equilibrative nucleoside transporter-1 and molecular mechanisms influencing its expression and activity…
2020
Simple Summary Despite the enormous advance in biomarker discovery, many potential biomarkers of drug activity are unable to satisfy the clinical need due to inadequate sensitivity and specificity. The nucleoside transporter hENT-1 has been studied as a potential biomarker to predict the effect of the widely used anticancer drug gemcitabine in pancreatic cancer. However, several studies showed controversial results regarding the predictive value of hENT-1, prompting new analyses with larger cohorts of patients and standardized methodologies. Improved insights on molecular mechanisms underlying hENT-1 expression and activity should also help in the identification of subsets of patients who a…
Trifluridine/tipiracil : an emerging strategy for the management of gastrointestinal cancers
2018
Fluoropyrimidines are currently the backbone of treatment for gastrointestinal (GI) cancers but development of resistance to these agents remains a major problem. Trifluridine/tipiracil is an oral chemotherapeutic agent recently approved for third-line treatment of chemorefractory metastatic colorectal cancer. This article reviews the clinical value of trifluridine/tipiracil as a monotherapy, including recent trials in GI cancers, and the potential benefit of combining it with other agents in patients with GI cancers, including the preclinical rationale for combination therapy and recently completed and ongoing clinical trials. Data gathered so far suggest that trifluridine/tipiracil has t…
Immuno-targeted combinations in oncogene-addicted non-small cell lung cancer
2018
The identification of tumor “oncogenic drivers” and the subsequent development of targeted therapy represented a milestone in the treatment of lung cancer over the last years. Tumor genotyping has been incorporated into therapeutic decision making of advanced non-small cell lung cancer (NSCLC) since has become clear that individuals with actionable molecular alterations receiving a matched targeted agent certainly live longer and better. The recent understanding of biological mechanisms underlying cancer immune evasion has allowed the development of a new class of immunomodulatory agents which are able to reactivate host immune-response, offering the potential for long-term disease control …
The effectiveness of combination chemotherapy with cisplatinum and etoposide in the treatment of advanced non-small cell lung cancer.
1989
Twenty-one patients with histologically proven advanced or disseminated non-small cell lung cancer were treated with cisplatinum 80 mg/m2 i.v. day 1 and etoposide (VP16) 80 mg/m2 i.v. day 1- greater than 3.15 patients were evaluable for response. One patient (6.6%) achieved a complete response, 4 (26.7%) a partial response and 6 (40.0%) a stabilization of disease. Four patients (26.7%) progressed. An improvement in performance status was obtained in more than 50% of cases. Responders had a mean survival of 345 + days, while non-responders 191.7 days. The treatment was generally well tolerated. In our opinion this combination regimen offers good palliation for patients affected by advanced a…