Purpose:Intratumoral hypoxia and immunity have been correlated with patient outcome in various tumor settings. However, these factors are not currently considered for treatment selection in head and neck cancer (HNC) due to lack of validated biomarkers. Here we sought to develop a hypoxia-immune classifier with potential application in patient prognostication and prediction of response to targeted therapy. Experimental Design:A 54-gene hypoxia-immune signature was constructed on the basis of literature...
10:05
Purpose:Cetuximab, which modulates immune responses, may affect the efficacy of subsequent immunotherapy. Here, we assessed outcomes with nivolumab, by prior cetuximab exposure, in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) who had experienced progression within 6 months of platinum-containing chemotherapy. Patients and Methods:In the randomized, open-label, phase III CheckMate 141 trial, patients were randomized 2:1 to nivolumab 3 mg/kg every...
10:05
Purpose:Perivascular epitheliod cell tumors (PEComas) are rare mesenchymal neoplasms for which the role of systemic treatments is not established as there are no published prospective clinical trials or sufficiently large retrospective case series. The aim of this study is to clarify the activity of conventional chemotherapy and biological agents in advanced/metastatic PEComas. Experimental Design:This was an observational, retrospective, international study that included patients with advanced/metastatic...
10:05
Purpose:This phase I study assessed the safety, tolerability, MTD, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in combination with capecitabine in patients with HER2-positive metastatic breast cancer (MBC). Patients and Methods:Patients received oral pyrotinib 160 mg, 240 mg, 320 mg, or 400 mg once daily continually plus capecitabine 1,000 mg/m2 twice daily on days 1 to 14 of a 21-day cycle. Pharmacokinetic blood samples were...
10:05
A Phase Ib/II Study of Ramucirumab in Combination with Emibetuzumab in Patients with Advanced Cancer
Purpose:Inhibition of the VEGFR-2 blocks angiogenesis and attenuates tumor growth, but cancers may evade this effect through activation of the hepatocyte growth factor receptor MET. Here we report results of the phase Ib/II study of ramucirumab, a monoclonal anti-VEGFR-2 antibody, plus the anti-MET mAb emibetuzumab. Patients and Methods:A 3+3 dose escalation of emibetuzumab plus ramucirumab (phase Ib) was followed by tumor-specific expansion cohorts. Primary objectives were to determine the recommended...
10:05
Purpose:Exercise after breast cancer diagnosis is associated with lower cancer-specific mortality, but the biological mechanisms through which exercise impacts breast cancer are not fully understood. The Pre-Operative Health and Body (PreHAB) Study was a randomized window-of-opportunity trial designed to test the impact of exercise on Ki-67, gene expression, and other biomarkers in women with breast cancer. Experimental Design:Inactive women with newly diagnosed breast cancer were randomized to...
10:05
Melanoma is among the most sensitive of malignancies to immune modulation. Although multiple trials conducted over decades with vaccines, cytokines, and cell therapies demonstrated meaningful responses in a small subset of patients with metastatic disease, a true increase in overall survival (OS) within a randomized phase III trial was not observed until the development of anti–CTLA-4 (ipilimumab). Further improvements in OS for metastatic disease were observed with the anti–PD-1–based therapies...
10:05
Purpose:Myeloid cells are a prominent immunosuppressive component within the stroma of pancreatic ductal adenocarcinoma (PDAC). Previously, targeting myeloid cells has had limited success. Here, we sought to target the myeloid cells through modifying a specific stromal component. Experimental Design:A murine model of metastatic PDAC treated with an irradiated whole-cell PDAC vaccine and PDAC specimens from patients treated with the same type of vaccine were used to assess the immune-modulating effect...
10:05
A key mechanism of resistance to chimeric antigen receptor–modified T cells (CAR-T) is loss or downregulation of target antigens. Low antigen expression on cancer cells prevents full CAR-T-cell activation and persistence. Pharmacologic modulation of target antigen expression offers a novel therapeutic strategy to drive more potent and durable responses. See related article by Ramakrishna et al., p. 5329
10:05
Purpose:Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer, such as BRCA1 and BRCA2, account for less than 25% of familial cases of breast cancer. Recently, specific epigenetic modifications at BRCA1 have been shown to promote hereditary breast cancer, but the broader potential for epigenetic contribution to hereditary breast cancer is not yet well understood. Experimental...
10:05
New approaches are required for addressing the important and unmet need to expand the benefits of checkpoint blockade to patients with mismatch repair proficient colorectal cancer. Systematic profiling of the tumor immune microenvironment provides insights into potential mechanisms of resistance, predictive biomarkers, and novel combinatorial strategies for overcoming resistance. See related article by Llosa et al., p. 5250
10:05
The applied quantitative science pharmacometrics has significantly enhanced cancer therapeutics development. Pharmacometrics is now improving our understanding of complex diagnostics. Through the concept of convergence and methods of quantitative and systems pharmacology, pharmacometrics is poised to interconnect mathematical models of disease and therapy to advance cancer care. See related article by Colomban et al., p. 5342
10:05
Purpose:Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority of post-CD22 CART remissions are short and associated with reduction in CD22 expression. We evaluate the implications of low antigen density on the activity of CD22 CART and propose mechanisms to overcome antigen escape. Experimental Design:Using ALL cell lines with variable CD22 expression, we evaluate the...
10:05
Observational findings suggest exercise is associated with improved outcomes in early-stage breast cancer. However, whether exercise has biological activity in patients with breast cancer has not been investigated. Preoperative window of opportunity studies provide a setting in which to test the short-term effects of novel treatment strategies on validated surrogates. See related article by Ligibel et al., p. 5398
10:05
Purpose:Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed. Experimental Design:Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation...
10:05
In the Caribbean, green turtles graze seagrass meadows dominated by Thalassia testudinum through rotational grazing, resulting in the creation of grazed and recovering (abandoned) patches surrounded by ungrazed seagrasses. We evaluated the seagrass community and its environment along a turtle grazing gradient; with the duration of (simulated) grazing as a proxy for the level of grazing pressure. The grazing levels consisted of Short-term (4 months clipping), Medium-term (8 months clipping), Long-term...
Mon Sep 02, 2019 03:00
Millions of birds die in bird-window collisions in the United States each year. In specialized test settings, researchers have developed methods to alter window designs to mitigate collisions. However, few published studies provide pretest and posttest evaluations of mitigation treatment areas and untreated control areas on existing buildings. We initially monitored bird-window collisions at a single building on the University of Utah campus in Salt Lake City, Utah, USA, during winter 1 (November...
Mon Sep 02, 2019 03:00
The structure of the reproductive system of the sexual generation—males and oviparous females—of the pea aphid Acyrthosiphon pisum (Harris) (Hemiptera, Aphididae), a serious pest of cultivated plants of Fabaceae, was investigated. For the first time we describe the morphology, histology and ultrastructure of the reproductive system in both morphs of the sexual generation of aphids within one species, using light and fluorescent microscopy, as well as transmission and scanning electron microscopy....
Mon Sep 02, 2019 03:00
Zooplankton exported from lentic systems provision lotic systems with easily captured, consumed, and assimilated prey items. Previous studies have demonstrated that the community composition of zooplankton exports (CCZE) vary over time, which introduces temporal differences in lotic resource availability (zooplankton prey) in downstream habitats. In the study presented here, we monitored variation in CCZE from a polymictic reservoir outfall in response to physical–chemical and atmospheric conditions...
Mon Sep 02, 2019 03:00
Cognitive impairment often involves the decreased expression or hypofunction of alpha 7-type nicotinic acetylcholine receptors (α7 nAChRs). Agonists or positive allosteric modulators (PAMs) of α7 nAChRs are known to be potential treatments for dementias, different neurodegenerative disorders, pain syndromes and conditions involving inflammation. In some of these conditions, it is desirable to maintain the temporal precision of fast cholinergic events, while in others, this temporal precision is unnecessary....
Mon Sep 02, 2019 03:00
Osteoarthritis (OA) is the most common motor system disease in aging people, characterized by matrix degradation, chondrocyte death, and osteophyte formation. OA etiology is unclear, but long noncoding RNAs (lncRNAs) that participate in numerous pathological and physiological processes may be key regulators in the onset and development of OA. Because profiling of lncRNAs and their biological function in OA is not understood, we measured lncRNA and mRNA expression profiles using high-throughput microarray...
Mon Sep 02, 2019 03:00
The structure of ecological interactions is commonly understood through analyses of interaction networks. However, these analyses may be sensitive to sampling biases with respect to both the interactors (the nodes of the network) and interactions (the links between nodes), because the detectability of species and their interactions is highly heterogeneous. These ecological and statistical issues directly affect ecologists’ abilities to accurately construct ecological networks. However, statistical...
Mon Sep 02, 2019 03:00
The thylacine is popularly used as a classic example of convergent evolution between placental and marsupial mammals. Despite having a fossil history spanning over 20 million years and known since the 1960s, the thylacine is often presented in both scientific literature and popular culture as an evolutionary singleton unique in its morphological and ecological adaptations within the Australian ecosystem. Here, we synthesise and critically evaluate the current state of published knowledge regarding...
Mon Sep 02, 2019 03:00
Background The Asiatic wild dog or dhole (Cuon alpinus) is a highly elusive, monophyletic, forest dwelling, social canid distributed across south and Southeast Asia. Severe pressures from habitat loss, prey depletion, disease, human persecution and interspecific competition resulted in global population decline in dholes. Despite a declining population trend, detailed information on population size, ecology, demography and genetics is lacking. Generating reliable information at landscape level...
Mon Sep 02, 2019 03:00
Background Enterobacter cloacae (EC) is a Gram-negative bacterium that has been utilized extensively in biotechnological and environmental science applications, possibly because of its high capability for adapting itself and surviving in hazardous conditions. A search for the EC from agricultural and industrial areas that possesses high capability to tolerate and/or accumulate cadmium ions has been conducted in this study. Plausible mechanisms of cellular adaptations in the presence...
Mon Sep 02, 2019 03:00
Lonicera japonica flos (LJF), the dried flower buds of L. japonica Thunb., have been used in traditional Chinese herbal medicine for thousands of years. Recent studies have reported that LJF has many medicinal properties because of its antioxidative, hypoglycemic, hypolipidemic, anti-allergic, anti-inflammatory, and antibacterial effects. LJF is widely used in China in foods and healthcare products, and is contained in more than 30% of current traditional Chinese medicine prescriptions. Because of...
03:00
Spartina alterniflora is one of the most noxious invasive plants in China and many other regions. Exploring environmentally friendly, economic and effective techniques for controlling Spartina alterniflora is of great significance for the management of coastal wetlands. In the present study, different approaches, including mowing and waterlogging, mowing and tilling and herbicide application, were used to control Spartina alterniflora. The results suggest that the integrated approach of mowing and...
03:00
Perna viridis and P. canaliculus are economically and ecologically important species of shellfish. In this study, the complete ribosomal DNA (rDNA) unit sequences of these species were determined for the first time. The gene order, 18S rRNA–internal transcribed spacer (ITS) 1–5.8S rRNA–ITS2–28S rRNA–intergenic spacer (IGS), was similar to that observed in other eukaryotes. The lengths of the P. viridis and P. canaliculus rDNA sequences ranged from 8,432 to 8,616 bp and from 7,597 to 7,610 bp, respectively,...
03:00
Objective Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. Methods Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms...
03:00
Abstract Purpose The clinical significance of cytokeratin fraction 21-1 (CYFRA 21-1) for patients with head and neck cutaneous squamous cell carcinoma (CSCC) is unknown. Thus, the aim of the study was to evaluate the clinical value of CYFRA 21-1 in the context of treatment and follow-up for these patients. Methods The clinical, histological and laboratory...
03:00
Abstract Purpose Different authors have reported that aging could be associated with changes in obstructive sleep apnea (OSA) related parameters (apnea/hypopnea index, SpO2, reduction of daytime sleepiness, etc.), type of sleep and pattern of collapse. Regarding OSA severity in elderly patients, it is commonly believed that the AHI score tends to increase with aging. Methods...
03:00
Cancers, Vol. 11, Pages 1296: What Is the Fuss about Integrins and the Tumor Microenvironment? Cancers doi: 10.3390/cancers11091296 Authors: Johannes A. Eble Donald Gullberg In recent years the tumor microenvironment (TME) has received increasing attention [...]
03:00
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου