Insulin-like growth factor (IGF)-1 is a potent mitogen, but IGF binding protein (IGFBP)-3 inhibits IGF1. To elucidate the relationship between both IGF1 and IGFBP and the risk of tumorigenesis, the association between IGF1 and IGFBP3 serum levels and of malignant tumor incidence was investigated in a prospective case–control study nested in the Japan Collaborative Cohort Study. A baseline survey was started in 1988–1990, 110,585 subjects were enrolled, and 35% of participants donated blood samples....
Thu Apr 02, 2020 10:05
Human behavior plays a central role in cancer-related morbidity and mortality. Much behavior is, in turn, attributable to several core biological, cognitive, emotional, motivational, and interpersonal processes. Understanding the systematic and interactive impact of these processes can inform efforts to address cancer-relevant outcomes such as tobacco use, reliance on cancer misinformation, engagement in genetic testing, adherence to treatment, and acceptance of palliative care. Here, we review efforts...
Thu Apr 02, 2020 10:05
A massive portion of cancer burden is accounted for by a small collection of highly prevalent cancer risk behaviors (e.g., low physical activity, unhealthy diet, and tobacco use). Why people engage in numerous types of cancer risk behaviors and fail to adopt various cancer prevention behaviors has been poorly understood. In this commentary, we propose a novel scientific framework, which argues that a common affective (i.e., emotion based) mechanism underpins a diversity of such cancer risk and prevention...
Thu Apr 02, 2020 10:05
The aim of this work was to evaluate the risk factors for recurrence in young patients with atypical endometrial hyperplasia and early-stage endometrioid adenocarcinoma after fertility-sparing treatments (FST). A retrospective case–control study was designed. Patients with atypical endometrial hyperplasia and early-stage endometrioid adenocarcinoma who received FSTs from January 2010 to December 2017 were reviewed. All patients who met the inclusion criteria were divided into a recurrence group and...
Thu Apr 02, 2020 10:05
Immune checkpoint blockade therapy provides substantial benefits for subsets of patients with advanced cancer, but its utility for cancer prevention is unknown. Lynch syndrome (MIM 120435) is characterized by defective DNA mismatch repair and predisposition to multiple cancers. A variant of Lynch syndrome, Muir–Torre syndrome (MIM 158320), is characterized by frequent gastrointestinal tumors and hyperplastic or neoplastic skin tumors. We report the case of a man with Muir–Torre syndrome who had 136...
Thu Apr 02, 2020 10:05
Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population "at risk" compared with the normal population are needed. In a cross-sectional analysis,...
Thu Apr 02, 2020 10:05
We previously reported that the environmental pollutant and tobacco smoke constituent dibenzo[def,p]chrysene (DBP) induced DNA damage, altered DNA methylation and induced oral squamous cell carcinoma (OSCC) in mice. In the present study, we showed that 5% dietary black raspberry (BRB) significantly reduced (P < 0.05) the levels of DBP-DNA adducts in the mouse oral cavity with comparable effect to those of its constitutes. Thus, only BRB was selected to examine if aberrant DNA methylation induced...
Thu Apr 02, 2020 10:05
Low Colorectal Cancer Screening Uptake and Persistent Disparities in an Underserved Urban Population
Colorectal cancer screening has increased substantially in New York City in recent years. However, screening uptake measured by telephone surveys may not fully capture rates among underserved populations. We measured screening completion within 1 year of a primary care visit among previously unscreened patients in a large urban safety-net hospital and identified sociodemographic and health-related predictors of screening. We identified 21,256 patients ages 50 to 75 who were seen by primary care...
Thu Apr 02, 2020 10:05
Longer-than-annual screening intervals have been suggested to improve the balance of benefits and harms in prostate cancer screening. Many researchers, societies, and guideline committees have suggested that screening intervals could depend on the prostate-specific antigen (PSA) result. We analyzed data from men (N = 33,897) ages 55–74 years with a baseline PSA test in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial (United States, 1993–2001). We estimated...
Thu Apr 02, 2020 10:05
Tamoxifen reduces breast cancer incidence in women at increased risk, but may cause side effects. We examined women's knowledge of tamoxifen's potential harms and benefits, and the extent to which knowledge reflects subjective judgments of awareness and decision quality. After a hospital appointment, 408 (55.7%) women at increased risk of breast cancer completed a survey assessing objective knowledge about the potential benefit (risk reduction) and harms (endometrial cancer, thromboembolic events,...
Thu Apr 02, 2020 10:05
Technology in Cancer Research &Treatment, Volume 19, Issue , January-December 2020. Objectives:The aim of the present study was to evaluate the clinical relevance of mutations in tumor suppressor genes using whole-exome sequencing data from centenarians and young healthy individuals.Methods:Two pools, one of centenarians and one of young individuals, were constructed and whole-exome sequencing was performed. We examined the whole-exome sequencing data of Bulgarian individuals for carriership...
Wed Apr 01, 2020 13:43
Technology in Cancer Research &Treatment, Volume 19, Issue , January-December 2020. Increasing evidence indicates the pivotal role of long noncoding RNAs in a variety of cancers, but there is limited focus on the link between long noncoding RNAs and gestational choriocarcinoma. This study aimed to examine the role of long noncoding RNA OGFRP1 in JEG-3 and JAR cells. Small interfering RNA was used to downregulate long noncoding RNA OGFRP1 level. Cell proliferation was measured by cell counting...
Wed Apr 01, 2020 13:40
Up to 50% of patients with uveal melanoma (UM) develop metastatic disease, for which there is no effective systemic treatment. This study aimed to evaluate the safety and efficacy of the orally available protein kinase C inhibitor, AEB071, in patients with metastatic UM, and to perform genomic profiling of metastatic tumor samples, with the aim to propose combination therapies. Patients with metastatic UM (n = 153) were treated with AEB071 in a phase I, single-arm study. Patients received total daily...
Thu Apr 02, 2020 10:05
Thu Apr 02, 2020 10:05
FOLFOX is one of the most effective treatments for advanced colorectal cancer. However, cumulative oxaliplatin neurotoxicity often results in halting the therapy. Oxaliplatin functions predominantly via the formation of toxic covalent drug–DNA adducts. We hypothesize that oxaliplatin–DNA adduct levels formed in vivo in peripheral blood mononuclear cells (PBMC) are proportional to tumor shrinkage caused by FOLFOX therapy. We further hypothesize that adducts induced by subtherapeutic "diagnostic microdoses"...
Thu Apr 02, 2020 10:05
HER2 is a transmembrane tyrosine kinase receptor that mediates cell growth, differentiation, and survival. HER2 is overexpressed in approximately 20% of breast cancers and in subsets of gastric, colorectal, and esophageal cancers. Both antibody and small-molecule drugs that target HER2 and block its tyrosine kinase activity are effective in treating HER2-driven cancers. In this article, we describe the preclinical properties of tucatinib, an orally available, reversible HER2-targeted small-molecule...
Thu Apr 02, 2020 10:05
Full-length antibodies lack ideal pharmacokinetic properties for rapid targeted imaging, prompting the pursuit of smaller peptides and fragments. Nevertheless, studying the disposition properties of antibody-based imaging agents can provide critical insight into the pharmacology of their therapeutic counterparts, particularly for those coupled with potent payloads. Here, we evaluate modulation of binding to the neonatal Fc receptor (FcRn) as a protein engineering-based pharmacologic strategy to minimize...
Thu Apr 02, 2020 10:05
The CD137 receptor plays a key role in mediating immune response by promoting T cell proliferation, survival, and memory. Effective agonism of CD137 has the potential to reinvigorate potent antitumor immunity either alone or in combination with other immune-checkpoint therapies. In this study, we describe the discovery and characterization of a unique CD137 agonist, 7A5, a fully human IgG1 Fc effector-null monoclonal antibody. The biological properties of 7A5 were investigated through in vitro and...
Thu Apr 02, 2020 10:05
H-Ras is a unique isoform of the Ras GTPase family, one of the most prominently mutated oncogene families across the cancer landscape. Relative to other isoforms, though, mutations of H-Ras account for the smallest proportion of mutant Ras cancers. Yet, in recent years, there have been renewed efforts to study this isoform, especially as certain H-Ras–driven cancers, like those of the head and neck, have become more prominent. Important advances have therefore been made not only in the understanding...
Thu Apr 02, 2020 10:05
CD137 (TNFRSF9, 4-1BB) agonist antibodies (mAb) have demonstrated potent antitumor activity with memory response while causing hepatotoxicity in mouse models. In clinical trials, the degrees of liver toxicity of anti-CD137 vary from grade 4 transaminitis (urelumab) to nonexistent (utomilumab). To exploit the antitumor potential of CD137 signaling, we identified a new class of CD137 agonist mAbs with strong antitumor potency without significant transaminitis in vivo compared with CD137 agonists previously...
Thu Apr 02, 2020 10:05
Hypoxia is a major factor in tumor progression and resistance to therapies, which involves elevated levels of the transcription factor HIF1α. Here, we report that prostate tumor xenografts express high levels of HIF1α and show greatly enhanced growth in response to knockdown of the E3 ligase CHIP (C-terminus of Hsp70-interacting protein). In multiple human prostate cancer cell lines under hypoxia, taxol treatment induces the degradation of HIF1α, and this response is abrogated by knockdown of CHIP,...
Thu Apr 02, 2020 10:05
Androgen deprivation therapy and second-generation androgen receptor signaling inhibitors such as enzalutamide are standard treatments for advanced/metastatic prostate cancer. Unfortunately, most men develop resistance and relapse; signaling via insulin-like growth factor (IGF) has been implicated in castration-resistant prostate cancer. We evaluated the antitumor activity of xentuzumab (IGF ligand–neutralizing antibody), alone and in combination with enzalutamide, in prostate cancer cell lines (VCaP,...
Thu Apr 02, 2020 10:05
Natural killer (NK) cells play a pivotal role in controlling cancer. Multiple extracellular receptors and internal signaling nodes tightly regulate NK activation. Cyclin-dependent kinases of the mediator complex (CDK8 and CDK19) were described as a signaling intermediates in NK cells. Here, we report for the first time the development and use of CDK8/19 inhibitors to suppress phosphorylation of STAT1S727 in NK cells and to augment the production of the cytolytic molecules perforin and granzyme B...
Thu Apr 02, 2020 10:05
High-throughput construction of multivalent binders and subsequent screening for biological activity represent a fundamental challenge: A linear increase of monovalent components translates to the square of possible bivalent combinations. Even high-efficiency cloning and expression methods become limiting when thousands of bispecific binders need to be screened for activity. In this study, we present an in vitro method for the efficient production of flexibly linked bispecific binding agents from...
Thu Apr 02, 2020 10:05
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου