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Combination Therapy

Philippine Lucas, Serge Boulinguez, Vincent Sibaud, Loïc Mourey, Laurence Lamant, Carle Paul, Nicolas Meyer
BACKGROUND: Combined treatment with BRAF-V600 and MEK inhibitors has significantly improved progression-free and overall survival of patients with BRAF-mutated melanoma. Pattern of disease progression and outcomes in patients have not been fully characterized. METHODS: We conducted a single-center, retrospective, descriptive analysis of a cohort of 52 patients treated with BRAF-V600 + MEK inhibitors for advanced melanoma over a 12-month period. The aim of this study was to characterize disease progression, defined as metastatic pattern, disease kinetics, and response to subsequent therapies, in melanoma patients treated with BRAF-V600 + MEK inhibitors...
August 15, 2018: Dermatology: International Journal for Clinical and Investigative Dermatology
George Drosos, Fotini Ampatzidou, Pantelis Sarafidis, Theodoros Karaiskos, Athanasios Madesis, Afroditi K Boutou
BACKGROUND: Most studies evaluating predictors of renal replacement therapy (RRT) following cardiac surgery use arbitrary defined limits of preoperative serum creatinine. The aim of this study was to evaluate the effect of preoperative renal function using either estimated-glomerular filtration rate (eGFR) derived using Chronic Kidney Disease-Epidemiology (CKD-EPI) or serum creatinine alone as a predictor for RRT after cardiac surgery. METHODS: In this prospective cohort study, baseline, intraoperative, and postoperative data of all patients who underwent an elective, urgent, or emergency cardiac surgery between 2012 and 2016 in a single center were analyzed in order to identify multivariate parameters determining the need for RRT after surgery...
August 15, 2018: American Journal of Nephrology
Brinda Emu, Jeffrey Fessel, Shannon Schrader, Princy Kumar, Gary Richmond, Sandra Win, Steven Weinheimer, Christian Marsolais, Stanley Lewis
BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4. METHODS: In this single-group, open-label, phase 3 study, we enrolled 40 adults with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral therapies had failed. All the patients had a viral load of more than 1000 copies of HIV-1 RNA per milliliter. After a 7-day control period in which patients continued to receive their current therapy, a loading dose of 2000 mg of ibalizumab was infused; the viral load was quantified 7 days later...
August 16, 2018: New England Journal of Medicine
Masanori Kawakami, Xi Liu, Ethan Dmitrovsky
Aneuploidy is a hallmark of cancer. Defects in chromosome segregation result in aneuploidy. Multiple pathways are engaged in this process, including errors in kinetochore-microtubule attachments, supernumerary centrosomes, spindle assembly checkpoint (SAC) defects, and chromosome cohesion defects. Although aneuploidy provides an adaptation and proliferative advantage in affected cells, excessive aneuploidy beyond a critical level can be lethal to cancer cells. Given this, enhanced chromosome missegregation is hypothesized to limit survival of aneuploid cancer cells, especially when compared to diploid cells...
August 15, 2018: Annual Review of Pharmacology and Toxicology
Yixiang Xu, Jian Zhang, Huan Wang, Fei Mao, Keting Bao, Wenwen Liu, Jin Zhu, Xiaokang Li, Haiyan Zhang, Jian Li
Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases (MAOs) are promising therapy for Alzheimer's Disease (AD). Herein, a series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed and synthesized as dual inhibitors of ChEs and MAOs with other functions against AD. Most of these derivatives inhibited ChEs and MAOs with IC50 values in the micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of targeting the AChE (IC50 = 0.032 ± 0...
August 15, 2018: ACS Chemical Neuroscience
Małgorzata Dybowska, Monika Szturmowicz, Paweł Kuca, Barbara Kazanecka, Janusz Burakowski, Cezary Czajka, Franciszek Grzegorczyk, Renata Langfort, Barbara Burakowska, Piotr Rudziński, Witold Tomkowski
Background Neoplastic pericardial effusion (NPE) represents a common cause of morbidity and mortality in patient with cancer. NPE presents frequently as cardiac tamponade, requiring urgent pericardiocentesis or pericardiotomy, with subsequent pericardial fluid drainage. Despite high effectiveness of such procedures, the recurrence of effusion is noted in 30- 60% of patients. Intrapericardial therapy with cisplatin was found to be effective in NPE due to lung and breast cancer. Its role in cardiac tamponade due to renal cancer is unknown...
August 15, 2018: Advances in Respiratory Medicine
Rosa M Bruno, Stefano Taddei
No abstract text is available yet for this article.
August 15, 2018: European Journal of Preventive Cardiology
Gabriella Leung, Aleixo M Muise
The incidence of inflammatory bowel disease (IBD) is increasing worldwide, most notably in young children. The development of disease is a combination of several factors, including genetics, environment, the microbiota, and immune system. Recently, next-generation sequencing has allowed for the identification of novel genetic causes for intestinal disease, including pediatric inflammatory bowel disease (IBD). These IBD genes can generally be grouped into genes causing either primary immunodeficiency or intestinal epithelial defects (the focus of this review)...
September 1, 2018: Physiology
Ye Liu, Qing Tian, Jin Yang, Haining Wang, Tianpei Hong
AIMS: Evidence on the pancreatic safety of glucagon-like peptide-1 receptor agonist therapy has been limited. The objective of the study was to investigate this issue by pooling data on the incidence of acute pancreatitis and pancreatic cancer from four large-scale cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists. MATERIALS AND METHODS: Data were extracted from four published cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes, and pooled analysis was performed to evaluate the risk of acute pancreatitis and pancreatic cancer associated with glucagon-like peptide-1 receptor agonist treatment...
August 14, 2018: Diabetes/metabolism Research and Reviews
Xichuan Tang, Liwei Tan, Kun Shi, Jinrong Peng, Yao Xiao, Wenting Li, Lijuan Chen, Qian Yang, Zhiyong Qian
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell...
July 2018: Acta Pharmaceutica Sinica. B
Zhiqiang Zhang, Xiaoran Guo, Kenneth K W To, Zhen Chen, Xiaona Fang, Min Luo, Chunling Ma, Jianhua Xu, Shirong Yan, Liwu Fu
Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells...
July 2018: Acta Pharmaceutica Sinica. B
Shin-Yi Chung, Yen-Hsi Chen, Pei-Rong Lin, Ta-Chung Chao, Jung-Chen Su, Chung-Wai Shiau, Yeu Su
Signal transducer and activator of transcription 3 (STAT3) has been shown to play a critical role in the maintenance of cancer stem cells (CSCs). Hence, the inhibition of STAT3 signaling has been suggested to be a viable therapeutic approach for cancers. Moreover, the efficacy of combinations of chemotherapeutic drugs and napabucasin, a small-molecule STAT3 inhibitor, have been assessed in various clinical trials, including those involving patients with metastatic colorectal cancer (CRC). Two recently developed small-molecule STAT3 inhibitors, SC-43 and SC-78, which can stimulate SHP-1 to inactivate STAT3, were found to have anti-tumor activity...
2018: Cell Death Discovery
Amir Awwad, Renan E Ibrahem Adam, Chandni Patel, James D Thomas
Introduction: Spinal epidural lipomatosis (SLE) is an abnormal accumulation of unencapsulated fat. The association of chronic steroid therapy is described as well as obesity and Cushing's syndrome. SLE has a range of neurological presentations such as back pain, myelopathy, and cauda equina syndrome. Surgical decompression is known to improve symptomatic cases and prevent further deterioration. Case presentation: An elderly male patient with background history of high-risk metastatic prostate cancer and long-term treatment with steroids and hormonal therapy presented with acute on chronic back pain and neurological symptoms...
2018: Spinal Cord Series and Cases
Rui Xie, Pingwah Tang, Qipeng Yuan
Histone deacetylases (HDACs) play a key role not only in gene expression but also in DNA repair. Herein, we report the rational design and characterization of a compound named chlordinaline containing nitrogen mustard and 2-aminobenzamide moieties as a DNA/HDAC dual-targeting inhibitor. Chlordinaline exhibited moderate total HDAC inhibitory activity. The HDAC isoform selectivity assay indicated that chlordinaline mostly inhibits HDAC3. Chlordinaline exhibited both DNA and HDAC inhibitory activities and showed potent antiproliferative activity against all the six test cancer cell lines with IC50 values of as low as 3...
February 1, 2018: MedChemComm
Marcel König, Daniel Siegmund, Lukasz J Raszeja, Aram Prokop, Nils Metzler-Nolte
Emerging resistances of tumors against multiple anti-cancer agents are a major concern in the chemotherapeutical treatment of various cancers. Clearly, this raises the need for novel therapeutics with new modes of action. Herein, we report on the favorable in vitro anti-proliferative properties of a phenanthridine-containing ReI (CO)3 complex (compound 1 , also abbreviated LR-166) and identify major contributions to its mode of action. The complex induces apoptosis in low micromolar concentrations even in drug-resistant Burkitt-like lymphoma (BJAB) and leukemia (Nalm-6) cell lines with known overexpression of p -glycoproteins as was confirmed by measuring the amount of hypodiploid DNA via FACS Scan analysis...
January 1, 2018: MedChemComm
Weining Niu, Fei Chen, Jun Wang, Jing Qian, Shasha Yan
Cystathionine β-synthase (CBS) overexpression is related to the proliferation and migration of human colon cancers. Targeted therapy that inhibits CBS has achieved promising effects in colon cancer treatments, but no selective inhibitor of CBS is available. In our previous study, a natural biflavonoid compound, sikokianin C, was identified as a potent and selective inhibitor of CBS. However, the mode of action of this compound and its antitumor efficacy in vivo remain unknown. In the present study, we have demonstrated that sikokianin C selectively inhibits CBS activity in a competitive manner, and the five key residues involved in the binding of sikokianin C to the substrate channel of CBS protein were identified via a combination of molecular docking and site-directed mutagenesis...
January 1, 2018: MedChemComm
Aijaz Ahmad, Mohmmad Younus Wani, Mrudula Patel, Abilio J F N Sobral, Adriano G Duse, Faisal Mohammed Aqlan, Abdullah Saad Al-Bogami
The occurrence of invasive fungal diseases, particularly in immunocompromised patients, is life-threatening and increases the economic burden. The rising problem of multi-drug resistance is becoming a major concern for clinicians. In addition, a repertoire of antifungal agents is far less in number than antibacterial drugs. To combat these problems, combination therapy has gained a lot of interest. We previously reported the synergistic interaction of some mono- and bis-dihydropyrimidinone and thione derivatives with fluconazole and amphotericin B for combination antifungal therapy...
December 1, 2017: MedChemComm
Mohsen Yaghubi, Hossein Dinpanah, Fahimeh Ghanei-Motlagh, Samaneh Kakhki, Reza Ghasemi
BACKGROUND: Amyloidosis is a severe systemic disorder produces by the accumulation of inappropriately amyloid deposition in tissues. Cardiac involvement, as a main type of amyloidosis, has a major impact on prognosis. We describe a biopsy-proven cardiac amyloidosis in an old man with unexpected presentation. CASE REPORT: A 70-year-old man, with a complaint of severe weakness, lightheadedness, and lower limb paresthesia, was admitted to the emergency department. Electrocardiography revealed right bundle branch block and Trifascicular block...
March 2018: ARYA Atherosclerosis
Ana Oliveira, Jéssica C Sousa, Ana C Silva, Luís D R Melo, Sanna Sillankorva
Chronic skin wounds represent a major burn both economically and socially. Pseudomonas aeruginosa and Escherichia coli are among the most common colonizers of infected wounds and are prolific biofilm formers. Biofilms are a major problem in infections due to their increasingly difficult control and eradication, and tolerance to multiple prescribed drugs. As so, alternative methods are necessary. Bacteriophages (phages) and honey are both seen as a promising approach for biofilm related infections. Phages have specificity toward a bacterial genus, species or even strain, self-replicating nature, and avoid dysbiosis...
2018: Frontiers in Microbiology
Mark McClure, Seerapani Gopaluni, David Jayne, Rachel Jones
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an organ-threatening and life-threatening multi-system autoimmune disease in which B cell-derived ANCAs cause neutrophil activation and endothelial damage, strongly implicating these autoantibodies in the pathogenesis of AAV. B cell depletion with rituximab combined with glucocorticoids is associated with a reduction in ANCA concentrations and with clinical remission in the majority of patients with AAV. However, the safety profile of rituximab is no better than that of conventional therapy with cyclophosphamide, and long-term glucocorticoid treatment is needed to achieve and maintain disease-free remission...
August 14, 2018: Nature Reviews. Rheumatology
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