14,460 research outputs found
Evaluating the number of stages in development of squamous cell and adenocarcinomas across cancer sites using human population-based cancer modeling.
No full textBACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site
Programmed chemotherapy for patients with metastatic unresectable gastric cancer.
No full textBACKGROUND: Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313-506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153-287 days) and 95 days (95% CI: 28-136 days), respectively. Grade 3-4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred. CONCLUSIONS/SIGNIFICANCE: This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved
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Abstract 5872: CDK1-SOX9 axis contributes to chemotherapy resistance in gastric cancer
No full textAbstract Gastric carcinoma (GC) is the third most prevalent cause of cancer-related mortality worldwide, presenting a formidable challenge with the rise of resistance to chemotherapeutic agents, leading to treatment failures. Cyclin-dependent kinase 1 (CDK1) has garnered attention due to its substantial overexpression in various tumors, including GC, and its association with poor overall survival and relapse-free survival. This study aimed to understand the molecular and functional mechanisms underlying the CDK1-SOX9 axis in GC chemotherapy resistance. Through a comprehensive analysis of data from The Cancer Genome Atlas (TCGA) and our own integrated gene expression study, we found a positive correlation between CDK1 and SOX9 in both human and mouse GC tissues (p<0.001). Additionally, conserved alterations in miRNAs have been identified in the context of gastric carcinogenesis, evident in our local cohort and the TCGA dataset. Our in-depth investigation of premiR-145 has shed light on the existence of several CpG nucleotides. Notably, treatment with a DNMT inhibitor (5-Aza) has triggered the upregulation of miR-145 expression. Furthermore, the ectopic expression of CDK1 has been associated with increased DNMT1 phosphorylation and enhanced enzymatic activity. Conversely, silencing CDK1 reversed this effect, and the inhibition of DNMT1 reduced SOX9 protein expression. Using cisplatin-resistant cell lines revealed a significant increase in CDK1 and SOX9 expression where silencing CDK1 and SOX9 sensitized these cells to chemotherapy. This study provides valuable insights into the intricate mechanisms governing the CDK1-SOX9 axis in GC chemotherapy resistance, providing potential avenues for therapeutic interventions in this challenging malignancy. Citation Format: Marwah M. Al-Mathkour, Shoumin Zhu, Melanie Genoula, Wael El-Rifai. CDK1-SOX9 axis contributes to chemotherapy resistance in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5872
Strain rate effect on twip/trip high entropy alloy
No full textA Master of Science thesis in Mechanical Engineering by Omar Mohammad Marwan El Batal entitled, “Strain rate effect on twip/trip high entropy alloy”, submitted in July 2021. Thesis advisor is Dr. Wael Abuzaid and thesis co-advisor Dr. Maen Abdelqabder Alkhader. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).High Entropy Alloys (HEA) present opportunities to develop new materials with outstanding mechanical properties. Through the careful selection of constituent elements along with optimized thermal processing for proper control of structure, grain size, and deformation mechanisms, many of the newly developed HEA systems exhibit superior strength and ductility levels across a wide range of temperatures, in particular at cryogenic deformation temperatures. Such a remarkable response has been attributed to the hardening capacity of HEA that is achieved through the activation of deformation twinning. More recent HEA compositions have considered phase transforming systems which have the potential for enhanced strengthening and therefore high strength and ductility levels. However, the strain rate sensitivity of such transforming HEA is not well understood and requires further investigation. In this study, the dynamic and quasi-static tensile properties of the non-equiatomic V10Cr10Fe45Co30Ni5 HEA were investigated temperatures ranging from 77K (196°C) to 573K (300°C).Depending on the deformation temperature, the considered HEA exhibits plasticity through either crystallographic slip, deformation twinning, or solid-state phase transformation. At 300°C, only slip mediated plasticity was observed for all the considered deformation rates. Deformation twinning was detected in samples deformed at room temperature (RT), while phase transformation, face-centered cubic to body-centered cubic, became more favorable at cryogenic deformation temperatures. At a deformation strain rate of 1.32e-3/sand 77K deformation temperature, the alloy reached an impressive tensile strength of around 1.2 GPa with a ductility exceeding 60%. Plastic deformation was accommodated in this case through phase transformation which consequently enabled superior strength and ductility. Both, the strain rate sensitivity (SRS) and strain hardening rates were shown to differ depending on the dominant deformation mechanism. For example, the SRS parameter m decreased as the deformation temperature dropped from RT (m = 0.05) to 77K (m = 0.017). Increasing the loading temperature to 300°C resulted in higher ductility, however at the expense of strength. Due to the absence of either twinning or transformation as hardening mechanisms, the HEA experienced a drop in strength reaching up to 23% at 300°C.College of EngineeringDepartment of Mechanical EngineeringMaster of Science in Mechanical Engineering (MSME
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First Record of Blister beetle Meloe rugosus M. (Coleoptera: Meloidae), as insect pest on some field crops in Farafra Oasis, Western Desert, Egypt
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A study of 214 neonates with infection in the Maternity and Children's Hospital of Riyadh, Saudi Arabia
No full textThis is a prospective study of 214 neonates admitted with suspected infection to the Maternity and Children's Hospital in Riyadh over the 15 months period, February 1980 to May 1981. Many of the infants showed clinical evidence of severe infection and 48 (22·4%) died, the highest mortality being among the low birth weight group, preterms and light-for-dates (33·3%). The infants tended to be from a low socio-economic class and bottle or mixed fed. The majority of their mothers were illiterate and many sought medical advice at a late stage. Recommendations are put forward to ensure that this vulnerable group receives a better standard of health education
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Some Calculations on Link Polynomials from 2-Parameter Quantum Groups
No full textStarting with the link invariant G (p,q,z) , a skein relation is introduced which enables us to calculate the polynomial starting with G (p,q,z) = 1, for the unknot. The relation between G (p,q,z) and the known 2-variable link invariant K (l,m) is shown. Then the polynomial of some common knots is calculated, also it is shown that this invariant failed to distinguish the Birmans pairs as well as Jones invariant
Delineation of signaling pathways induced by Helicobacter pylori that regulate host cell survival
No full textGastric adenocarcinoma is strongly associated with the presence of H. pylori. Microbial factors of H. pylori and host responses induced by the interactions of H. pylori with gastric epithelial cells play important roles in the development of disease. PI3K and β-catenin/p120 are multifunctional host proteins that coordinate carcinogenic epithelial responses when aberrantly activated, such as in malignant gastric lesions. We demonstrate that H. pylori infection results in upregulation of PI3K-AKT signaling, through stimulation of EGFR. Activation of this pathway reduces rates of epithelial cell death induced by H. pylori and promotes resistance to apoptosis. We also demonstrate that H. pylori infection induces additional host signaling pathways to potentiate a proliferative response in gastric epithelial cells. Specifically, PPARδ, a target of β-catenin transcriptional activation, contributes to increased rates of gastric epithelial cell proliferation in response to H. pylori infection. Based on these findings we hypothesize that an anti-apoptotic response in the presence of increased proliferation increases the risk of retaining mutagenized gastric epithelial cells in the presence of H. pylori induced gastritis. Taken together, these studies have identified effectors that directly mediate host responses related to carcinogenesis. Molecular delineation of such pathways activated by host-microbial interactions will improve our understanding of H. pylori-induced carcinogenesis, allowing for targeted therapies to high-risk individuals, as well as provide insight into other malignancies that arise within the context of pathogen-induced inflammation
Delineation of signaling pathways induced by Helicobacter pylori that regulate host cell survival
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