tbuckley/cabot-search huggingface dataset:
Abstract 3255: Inhibition of intracrine VEGF signaling prevents colorectal cancer cell migration and invasion
Authors: Rajat Bhattacharya, Ling Xia, Fan Fan, Rui Wang, Delphine Boulbes, Xiang-Cang Ye, Lee Ellis
Journal: Cancer Research (2016)

Abstract Introduction: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and vascular function. The mechanisms of VEGF signaling in angiogenesis have been extensively studied. However, its effects on tumor cell function remain to be elucidated. Our studies on depletion of VEGF by somatic knockout of the VEGF gene or by siRNA in human colorectal cancer (CRC) cell lines have demonstrated that loss of VEGF expression led to significantly decreased cell growth, increased apoptosis, and enhanced chemo-sensitivity of CRC cells through an intracrine signaling mechanism. These intracrine effects were mediated through VEGF by regulation of the activity of multiple receptor tyrosine kinases (e.g. EGFR, cMET) and downstream AKT signaling. Similar effects were observed by depletion of VEGF receptor 1 (VEGFR1), supporting the role of a novel intracellular VEGF-VEGFR1 complex in CRC cell survival. Since VEGF signaling has been shown to effect endothelial and tumor cell migration, we attempted to determine if inhibition of intracrine VEGF signaling affected CRC cell motility. Methods: Migration and invasion of CRC cells, with and without VEGF depletion, were assayed using Boyden chambers and a serum gradient. Changes in cell morphology and epithelial to mesenchymal transition (EMT) markers and markers of cell motility were assessed by microscopy, immunostaining, and western blot analyses. Results: Depletion of VEGF by siRNAs in multiple CRC cell lines led to a very strong inhibition of migration and invasion of CRC cells. Such inhibition was not observed when CRC cells were treated with bevacizumab to inhibit paracrine or autocrine signaling. Further examination revealed no significant changes in cell morphology. Other than Twist, there were no significant differences between specific markers of EMT indicating that differences in migration and invasion were not due to classic alterations in EMT. However, significant changes in activation of mediators of cell motility were observed. VEGF depleted CRC cells demonstrated significantly lower levels of phosphorylated focal adhesion kinase (p-FAK) compared to cells with normal VEGF expression. Analyses of upstream regulators indicated strong reduction in either p-cMET or p-SRC depending on cell type. Conclusions: Inhibition of intracrine VEGF signaling strongly inhibits CRC cell migration and invasion by regulating proteins involved in cell motility. Citation Format: Rajat Bhattacharya, Ling Xia, Fan Fan, Rui Wang, Delphine Boulbes, Xiang-Cang Ye, Lee Ellis. Inhibition of intracrine VEGF signaling prevents colorectal cancer cell migration and invasion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3255.
NCI Launches Cancer Patient Data Repository
Authors: Jennifer Abbasi
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Irritable bowel syndrome, the microbiota and the gut-brain axis
Authors: Hans Raskov, Jakob Burcharth, Hans-Christian Pommergaard, Jacob Rosenberg
Journal: Gut Microbes (2016)

Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome.
A Challenge in Vaccine Development —<i>Neisseria meningitidis</i>Serogroup B
Authors: Jerome H. Kim
Journal: New England Journal of Medicine (2016)

Proving the clinical efficacy of Neisseria meningitidis serogroup B (MenB) vaccines has been difficult. There is substantial genetic (and corresponding antigenic) diversity, and serogroup B meningococcal disease is both uncommon and in decline in countries where the burden is well understood. The incidence of meningococcal disease in the United States is at a historic low (0.18 per 100,000 person-years in 2013, including serotypes A, C, W, Y, and B). However, from 2009 through 2015 there were seven outbreaks of MenB meningitis at U.S. universities that resulted in 43 cases and 3 deaths.1 Because no MenB vaccine had been approved by . . .
PI3K/Akt/mTOR Signaling and Plasma Membrane Proteins Are Implicated in Responsiveness to Adjuvant Dendritic Cell Vaccination for Metastatic Colorectal Cancer
Authors: David C. Qian, Xiangjun Xiao, Jinyoung Byun, Arief A. Suriawinata, Stephanie C. Her, Christopher I. Amos, Richard J. Barth
Journal: Clinical Cancer Research (2016)

We have previously demonstrated that patients with metastatic colorectal cancer who exhibit immune responses to a dendritic cell (DC) vaccine have superior recurrence-free survival following surgery, compared with patients in whom responses do not occur. We sought to characterize the patterns of T-lymphocyte infiltration and somatic mutations in metastases that are associated with and predictive of response to the DC vaccine.Cytotoxic, memory, and regulatory T cells in resected metastases and surrounding normal liver tissue from 22 patients (11 responders and 11 nonresponders) were enumerated by immunohistochemistry prior to vaccine administration. In conjunction with tumor sequencing, the combined multivariate and collapsing method was used to identify gene mutations that are associated with vaccine response. We also derived a response prediction score for each patient using his/her tumor genotype data and variant association effect sizes computed from the other 21 patients; greater weighting was placed on gene products with cell membrane-related functions.There was no correlation between vaccine response and intratumor, peritumor, or hepatic densities of T-cell subpopulations. Associated genes were found to be enriched in the PI3K/Akt/mTOR signaling axis (P < 0.001). Applying a consistent prediction score cutoff over 22 rounds of leave-one-out cross-validation correctly inferred vaccine response in 21 of 22 patients (95%).Adjuvant DC vaccination has shown promise as a form of immunotherapy for patients with metastatic colorectal cancer. Its efficacy may be influenced by somatic mutations that affect pathways involving PI3K, Akt, and mTOR, as well as tumor surface proteins. Clin Cancer Res; 23(2); 399-406. ©2016 AACR.
Abstract 254: Lung cancer cells growing under prolonged period of serum starvation display increased stemness
Authors: Rajkumar Venkatadri, Juan Sebastian Yakisich, Neelam Azad, Anand Krishnan V. Iyer.
Journal: Cancer Research (2016)

Abstract Purpose: Resistance to anticancer drugs is a common cause of failure in chemotherapy. We recently found that adherent cells growing under prolonged periods (7-12 days) of serum starvation become highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea and Colchicine but retain sensitivity to therapeutic levels of the cardiac glycoside Digitoxin. Objectives: The main goal of this study is to characterize the biological properties of cells growing under prolonged periods of serum starvation (PPSS), and to elucidate the underlying mechanism of chemoresistance to Paclitaxel and sensitivity to Digitoxin with particular emphasis on Sox2 and the PI3K/AKT signaling pathway. Experimental setup: Distribution of cell cycle was characterized by flow cytometry. Cell viability was assessed using the MTT assay. Western blotting was employed to evaluate the expression of several key protein markers of cancer stemness (Sox2, Wnt), multidrug resistance (MDR1, ABCG2), epithelial mesenchymal transition (Vimentin), and cell survival (Bcl-2, XIAP, PI3K/AKT). Results: Cells grown under PPSS showed a higher proportion of cells in G1/S and G2 compared to cells growing under routine culture conditions (RCCs). Western blot analysis showed that these cells expressed higher levels of Sox2, MDR1, ABCG2, Bcl-2 compared to cells growing under RCCs. Pretreatment of cells for 3 h with Verapamil or Sorafenib (MDR1 and ABCG2 inhibitors, respectively) followed by co-incubation with Paclitaxel for 72 h did not overcome Paclitaxel resistance. Obatoclax (a Bcl-2 inhibitor), Wortmannin or LY294002 (PI3K inhbitors) also failed to overcome Paclitaxel resistance. It was interesting to observe that cells growing under PPSS were highly resistant to Obatoclax, Wortmannin and LY294002 compared to cells growing under RCCs. However, these cells were highly sensitive to treatment with Digitoxin. Conclusions: It is likely that multiple mechanisms (increased stemness, overexpression of multidrug resistance protein and prosurvival proteins) contributes to the resistance of cells under PPSS to Paclitaxel, Obatoclax and PI3K inhibitors. Preliminary results indicates that Digitoxin exerts its antiproliferative effect in part by downregulating Sox2. However, the lack of effect of Wortmannin and LY294002 on Paclitaxel resistance suggests that this effect is not via the PI3K/AKT pathway. Adherent cells growing under PPSS provide a simple yet powerful system to screen for drugs targeting cancer stemness. Citation Format: Rajkumar Venkatadri, Juan Sebastian Yakisich, Neelam Azad, Anand Krishnan V. Iyer. Lung cancer cells growing under prolonged period of serum starvation display increased stemness. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 254.
Abstract 2843: TASC1, a selective anti-senescence therapeutic which potently and selectively counteract resistance to chemo- and radiotherapy
Authors: Marjolein P. Baar, Diana A. Putavet, Joris Pothof, Jan H.J. Hoeijmakers, Peter L.J. de Keizer.
Journal: Cancer Research (2016)

Abstract Resistance to therapy is a major limitation towards the cure of irresectable cancer. Cellular senescence, induced by chemotherapy and radiotherapy, can drive therapy resistance in vivo. Senescence is a tumor suppressive mechanism, but senescent cells can secrete a range of proteins that ironically promote tumor growth, migration and metastazation and therapy resistance. Recent evidence has shown that genetic removal of senescent cells indeed causes a strong reduction in tumor growth and metastasis formation. Unfortunately however, therapeutic options to remove senescent cells are currently lacking. Here, we show the development and optimization of a biochemical compound, TASC1, that potently and selectively kills senescent cells in vitro and in vivo and lowers organ toxicity in a mouse model employed to address the off-target effects of cancer therapy. This encouraged us to test the effect of TASC1 against cancer therapy resistance. We focused on Glioblastoma multiforme (GBM), the most aggressive and lethal stage of glioma (III-IV) with a median survival of less than 15 months. Treatment of GBM involves a combination of surgery, radiotherapy and adjuvant chemotherapy (Temozolomide). Response to radiotherapy is generally strong, but resistance occurs rapidly, after which currently no successful follow-up treatment exists. We observed radiation therapy to induce senescence in astrocytes and senescence-like effects in GBM cells, without affecting their progression. Strikingly, while both TASC1 and radiation at various doses independently failed to reduce growth of these GBM cells, the combination of TASC1 with radiation showed a potent synthetic lethal response. Similar effects were seen for other types of cancer and their respective therapies. Thus, TASC1 is a potent adjuvant to (re)sensitize therapy-resistance metastatic cancer cells to treatment. Citation Format: Marjolein P. Baar, Diana A. Putavet, Joris Pothof, Jan H.J. Hoeijmakers, Peter L.J. de Keizer. TASC1, a selective anti-senescence therapeutic which potently and selectively counteract resistance to chemo- and radiotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2843.
Abstract 2399: System analysis of adapted and quiescent/dormancy(QD) models of drug resistance in melanoma cell lines
Authors: Feng Liu, Parvita Paresh Panchal, Zi Wang, Ahmed Farhat, Angela Garcia, Tcharles Fagundes, Fabian Filipp, Frank L. Meyskens
Journal: Cancer Research (2016)

Abstract The biological basis for inherent and acquired drug resistance in melanoma is a prominent issue, highlighted by the recent discovery of various pathways leading to acquired resistance to the mutant BRAF inhibitor Vemurafenib (Plx4032). In order to dissect patterns of drug resistance, we treated 3 melanoma cell lines (A375, 1205Lu and SK-Mel28) under 2 diverse conditions: (1) Increasing drug concentrations over time(4 months)- Melanoma cells treated with increasing concentrations of Plx4032 (initial and increasing concentrations of 0.1, 0.5, 1 and 5 μM PLx4032) exhibited an adaptation response. After an initial pause in proliferation, these cells proliferated in the continuing presence of the drug. Cells able to grow in the presence of 10 or 20 μM of Plx4032 were cultured as pools. RNA-Seq profiling and system biology analysis comparing the gene expression in the parental SK-Mel28 cells and adapted A2-1 revealed three major altered pathways: the PDGF-MAPK-DUSP-HIF2α, TGF-β-SMAD9-FGF1 and EDNRB-GNAI2-PLCB4-PKA-MITF pathway. Our qRT-PCR and western blot experiments have confirmed an up-regulation of PDGF which by-passed the BRAF gene and activated ERK1/2 kinases. These changes were accompanied by increase of NRAS accumulation in the adapted cells. (2) Using high initial drug concentrations of PLx4032 (&amp;gt;10 μM), &amp;gt; 99.9 of cells were killed, but some single cells (Q/D) survived for at least 4 weeks in the continuous presence of drug. After the drug was removed cellular proliferation reoccured 2-3 weeks later (designated post-dormant cells 1, PD1 cells). These cells did not show increased IC50s to Plx4032 after 72 hour of retreatment. However, when treated with high dose of drug again, the PD1 cells produced more dormant cells (PD2 cells), suggesting inheritance of the DQ trait. RNA-Seq profiling studies of the DQ cells are underway. The drug-induced dormancy/quiescence and adaptive response represent 2 different pathways of how cells survive treatment and develop resistance and provide a beginning to understanding the biological basis of the well established clinical phenomenon of long term clinical dormancy of melanoma and potentially other cancers. Citation Format: Feng Liu, Parvita Paresh Panchal, Zi Wang, Ahmed Farhat, Angela Garcia, Tcharles Fagundes, Fabian Filipp, Frank L. Meyskens. System analysis of adapted and quiescent/dormancy(QD) models of drug resistance in melanoma cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2399.
Krukenberg's tumor as the first clinical manifestation of cancer: A single institutional review of cases from 1993-2008 from South India.
Authors: V. S. Radhakrishnan
Journal: Journal of Clinical Oncology (2010)

e15541 Background: To analyze clinical data such as, presentation, diagnosis, treatment and follow up of patients presenting with Krukenberg's tumor as the first clinical manifestation of cancer to a single institution in South India. Methods: We retrospectively analyzed medical data from 41 patients who were referred to the Medical Oncology Department of the Institute of Obstetrics and Gynecology, Madras Medical College, Chennai between 1993 and 2008. Results: The patients ranged from 24 to 70 years (median, 45.5 years) with 41% of them being pre-menopausal. Abdominal distension or pain accounted for the commonest clinical presentation. Ascites was present in 49% of patients. 58% of the tumors were documented to be bilateral. Before a definitive diagnosis of ovarian tumor, investigations such as ultrasonography and chest X-Ray were undertaken in all patients. Computed tomography and CA-125 results were available for 13 patients. The highest level of CA-125 was 134 IU/mL. 27(66%) patients underwent surgery. The most common surgery performed was a debulking surgery. Microscopy suggested a digestive tract malignancy in 31 patients, ductal carcinoma in 5 patients, and mucinous adenocarcinoma in 5 patients. The details of the work-up for the primary site of cancer was available for all patients. Primary site of malignancy was stomach in 20 (48.4%) patients, colonic cancer in 7 (17%) patients, pancreatic cancer in 1 (2.4%) patient, breast cancer in 5 (12.2%) patients, lung cancer in 1 (2.4%) patient, and unknown primary site in 7 (17%) patients. 29 patients received Palliative chemotherapy. Follow-up data was available for 29 patients. The median overall survival was 7 months in our group of patients. Conclusions: There is poor prognosis for patients presenting with Krukenberg's tumor as the initial clinical manifestation of cancer. Bilateral ovarian tumor with ascites especially in premenopausal women should arouse suspicion. Diagnosis is late and most patients undergo surgery for ovarian tumor. The most common primary tumor is gastrointestinal tract cancer. No significant financial relationships to disclose.
Increased use of high-flow nasal oxygen during bronchoscopy
Authors: Beatrice La Combe, Jonathan Messika, Muriel Fartoukh, Jean-Damien Ricard
Journal: European Respiratory Journal (2016)

We thank P.S. Santos and co-workers for their interest in our study [1], and appreciate the opportunity given to us to further discuss our data. High flow oxygen maintains adequate oxygenation during fibre-optic bronchoalveolar lavage and prevents desaturation <http://ow.ly/4mQDHq>
Geographic Clusters of Basal Cell Carcinoma in a Northern California Health Plan Population
Authors: G. Thomas Ray, Martin Kulldorff, Maryam M. Asgari
Journal: JAMA Dermatology (2016)

Rates of skin cancer, including basal cell carcinoma (BCC), the most common cancer, have been increasing over the past 3 decades. A better understanding of geographic clustering of BCCs can help target screening and prevention efforts.Present a methodology to identify spatial clusters of BCC and identify such clusters in a northern California population.This retrospective study used a BCC registry to determine rates of BCC by census block group, and used spatial scan statistics to identify statistically significant geographic clusters of BCCs, adjusting for age, sex, and socioeconomic status. The study population consisted of white, non-Hispanic members of Kaiser Permanente Northern California during years 2011 and 2012.Statistically significant geographic clusters of BCC as determined by spatial scan statistics.Spatial analysis of 28 408 individuals who received a diagnosis of at least 1 BCC in 2011 or 2012 revealed distinct geographic areas with elevated BCC rates. Among the 14 counties studied, BCC incidence ranged from 661 to 1598 per 100 000 person-years. After adjustment for age, sex, and neighborhood socioeconomic status, a pattern of 5 discrete geographic clusters emerged, with a relative risk ranging from 1.12 (95% CI, 1.03-1.21; P = .006) for a cluster in eastern Sonoma and northern Napa Counties to 1.40 (95% CI, 1.15-1.71; P < .001) for a cluster in east Contra Costa and west San Joaquin Counties, compared with persons residing outside that cluster.In this study of a northern California population, we identified several geographic clusters with modestly elevated incidence of BCC. Knowledge of geographic clusters can help inform future research on the underlying etiology of the clustering including factors related to the environment, health care access, or other characteristics of the resident population, and can help target screening efforts to areas of highest yield.
Euphorbia factor L2 induces apoptosis in A549 cells through the mitochondrial pathway
Authors: Minting Lin, Sili Tang, Chao Zhang, Hubiao Chen, Wenjing Huang, Yun Liu, Jianye Zhang
Journal: Acta Pharmaceutica Sinica B (2016)

Euphorbia factor L2, a lathyrane diterpenoid isolated from caper euphorbia seed (the seeds of Euphorbia lathyris L.), has been traditionally applied to treat cancer. This article focuses on the cytotoxic activity of Euphorbia factor L2 against lung carcinoma A549 cells and the mechanism by which apoptosis is induced. We analyzed the cytotoxicity and related mechanism of Euphorbia factor L2 with an MTT assay, an annexin V-FITC/PI test, a colorimetric assay, and immunoblotting. Euphorbia factor L2 showed potent cytotoxicity to A549 cells. Euphorbia factor L2 led to an increase in reactive oxygen species (ROS) generation, a loss of mitochondrial electrochemical potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase, suggesting that Euphorbia factor L2 induced apoptosis through a mitochondrial pathway. The cytotoxic activity of Euphorbia factor L2 in A549 cells and the related mechanisms of apoptotic induction provide support for the further investigation of caper euphorbia seeds.