Introduction: Approximately 20% of patients living with colorectal cancer (CRC) have activating mutations in their tumors in the PIK3CA oncogene. Two or more activating mutations (multi-hit) for the PIK3CA allele increase PI3K⍺ signaling compared to single-point mutations, resulting in exceptional response to PI3K⍺ inhibition. We aimed to identify the prevalence of PIK3CA multi-hit mutations in metastatic CRC to identify patients who may benefit from PI3K inhibitors.
View Article and Find Full Text PDFmutations are common driver oncogenes associated with the development of several solid tumors. oncogene has been considered a highly challenging target for drug development because of structural features, including the lack of deep groove on its catalytic unit. However, by leveraging cysteine residues, covalent KRAS inhibitors irreversibly trap KRAS G12C mutants in their inactive GDP-bound state.
View Article and Find Full Text PDFBackground: Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.
Methods: Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.
Recent trials provide evidence that HER2 is a potential new target for patients with colorectal cancer. While HER2-positive tumors do not show a very encouraging response to anti-HER2-positive agents like trastuzumab alone, promising results have been observed when combined with other synergistically acting tyrosine kinase inhibitors (TKIs). Our meta-analysis was conducted following the Cochrane Handbook and written following the PRISMA guidelines.
View Article and Find Full Text PDFPurpose: O-methylguanine DNA methyltransferase ()-silenced tumors reveal sensitivity to temozolomide (TMZ), which may be enhanced by PARP inhibitors. Approximately 40% of colorectal cancer has silencing and we aimed to measure antitumoral and immunomodulatory effects from TMZ and olaparib in colorectal cancer.
Experimental Design: Patients with advanced colorectal cancer were screened for promoter hypermethylation using methylation-specific PCR of archival tumor.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm of mismatch repair-deficient/microsatellite instability-high (MMMR-D/MSI-H) colorectal cancer (CRC). Unique molecular features of MMR-D/MSI-H CRC with frameshift alterations, which result in mutation-associated neoantigen (MANA) generation, create an ideal molecular framework for MANA-driven T-cell priming and antitumor immunity. These biologic characteristics of MMR-D/MSI-H CRC resulted in rapid drug development with ICIs for patients with MMR-D/MSI-H CRC.
View Article and Find Full Text PDFis an opportunistic bacterial pathogen that has been shown to interact with many organisms throughout the domains of life, including plants. How this broad-host-range bacterium interacts with each of its diverse hosts, especially the metabolites that mediate these interactions, is not completely known. In this work, we used a liquid culture root infection system to collect plant and bacterial metabolites on days 1, 3 and 5 post-.
View Article and Find Full Text PDFBackground: Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer.
View Article and Find Full Text PDFNeuroendocrine tumors (NETs) are a heterogeneous clinical entity with a broad range of grade, pace of disease, functional status, and primary sites. Pathologic classification, diagnostic modalities, and therapeutic options for NETs have evolved considerably in the past decade. In part driven by these advances, incidence and prevalence of NETs are rising in the United States and the practicing oncologist is likely to encounter these in the clinic.
View Article and Find Full Text PDFThe rhizosphere microbiome is composed of diverse microbial organisms, including archaea, viruses, fungi, bacteria as well as eukaryotic microorganisms, which occupy a narrow region of soil directly associated with plant roots. The interactions between these microorganisms and the plant can be commensal, beneficial or pathogenic. These microorganisms can also interact with each other, either competitively or synergistically.
View Article and Find Full Text PDFInsects and pathogenic infections (bacteria, viruses and fungi) cause huge losses in agriculturally important crops yearly. Due to the rise in pesticide and antibiotic resistance, our crops and livestock are increasingly at risk. There is a rising demand for environmentally friendly solutions to prevent crop decreases.
View Article and Find Full Text PDFExposure to excess glucocorticoids during fetal development has long-lasting physiological and behavioral consequences, although the mechanisms are poorly understood. The impact of prenatal glucocorticoids exposure on stress responses in juvenile and adult offspring implicates the developing hypothalamus as a target of adverse prenatal glucocorticoid action. Therefore, primary cultures of hypothalamic neural-progenitor/stem cells (NPSCs) derived from mouse embryos (embryonic day 14.
View Article and Find Full Text PDFObjective: The purpose of this study was to compare outcomes of radioactive seed localization (RSL) versus wire localization using surgical margin size, reexcision and reoperation rates, specimen size, radiology resource utilization, and cosmesis as measures.
Materials And Methods: Patients who underwent RSL before segmental mastectomy from April 1, 2011, to March 1, 2012, for biopsy-proven cancer were selected. Each was matched using tumor size, type, and surgeon to a wire localization control case, resulting in 232 cases.
The life-threatening, emotional, and economic burdens of premature birth have been greatly alleviated by antenatal glucocorticoid (GC) treatment. Antenatal GCs accelerate tissue development reducing respiratory distress syndrome and intraventricular hemorrhage in premature infants. However, they can also alter developmental processes in the brain and trigger adverse behavioral and metabolic outcomes later in life.
View Article and Find Full Text PDF