tbuckley/cabot-search huggingface dataset:
Reduced cancer cell viability under methionine limiting conditions
Authors: Keith Booher, Peter Kaiser
Journal: Cancer Research (2007)

4456  Many different cancer cell types will undergo cell cycle arrest, followed by apoptosis when methionine is restricted from the growth media and substituted with its immediate metabolic precursor homocysteine (Met-Hcy+). In contrast, non-transformed cells will continue to grow normally in Met-Hcy+ media â\#8364;“ a phenomenon referred to as the methionine dependent phenotype of cancer cells. Methionine and homocysteine are metabolites in the transmethylation pathway, which leads to synthesis of the primary methyl-donor S-adenosylmethionine, and are thus essential to maintain the methylation potential of cells. We have used a colorimetric sulforhodamine B (SRB) assay to determine cell proliferation rates for various lines of cancer cells. All cancer cells tested showed a complete block of cell division in Met-Hcy+ media but divided rapidly in Met+Hcy+ or Met+Hcy- conditions. The cancer cellsâ\#8364;™ drastically reduced viability in growth media where homocysteine replaces methionine suggests a pathway containing potential drug targets to be exploited for therapeutic benefit. However, the molecular pathway that links the methionine/homocysteine effect to cell cycle progression is completely unknown. We have recently described a pathway in the model organism yeast that controls a cell cycle checkpoint in response to changes in metabolic profiles involving the transmethylation pathway. We are analyzing a similar pathway in mammalian cells. In addition, metabolic profile changes in cancer cells in response to methionine replacement by homocysteine will be important indicators for altered cell physiology in Met-Hcy+ medium.  We will present our results on the inhibition of cancer cell proliferation by homocysteine and describe our approaches to achieve a molecular understanding of the cancer-specific antiproliferative effect of Met-Hcy+ medium.
Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio
Authors: Roel S. Driessen, Guus A. de Waard, Wijnand J. Stuijfzand, Pieter G. Raijmakers, Ibrahim Danad, Michiel J. Bom, James K. Min, Jonathon A. Leipsic, Amir Ahmadi, Peter M. van de Ven, Juhani Knuuti, Albert C. van Rossum, Justin E. Davies, Niels van Royen, Jagat Narula, Paul Knaapen
Journal: JACC. Cardiovascular imaging (2019)
Abstract #2759: Thymoquinone-induced E2F-1 downregulation and induction of apoptosis enhances gemcitabine effects in pancreatic cancer
Authors: Ahmed Kaseb, KB Harikumar, AB Kunnumakkara, A Deorukhkar, James Abbruzzese, Sunil Krishnan, Bharat Aggarwal, Sushovan Guha
Journal: Cancer Research (2009)

Background: Response rates to gemcitabine (Gem), the most commonly used chemotherapy in pancreatic cancer (PC), remain quite low, which is partly due to de novo chemo-resistance, in addition to over-expression of ribonucleotide reductase M2 subunit (RR-M2), a rate-limiting enzyme in DNA synthesis that is regulated by E2F-1. Moreover, E2F-1 is a key transcriptional factor necessary for transition to S phase, cellular proliferation, viability, and has recently been correlated with poor differentiation and survival in PC. Thus, E2F-1 represents a unique therapeutic target in PC. We have previously reported E2F-1 targeted effects in prostate cancer using thymoquinone (TQ), an herbal agent that spares normal cells. Aim: The aim of our study was to determine the effects of TQ either alone or in combination with Gem in PC, both in vitro and in vivo. Methods and Results: We observed that TQ inhibited proliferation of PC cell lines (AsPC-1, BxPC3, MIAPaCa-2, and PANC-1) but not that of immortalized human pancreatic ductal epithelial (HPDE) cells. We showed that TQ synergistically potentiated pro-apoptotic effects of Gem in PC cell lines. Using PANC-1 (Gem-resistant) cells as our model system, we showed that TQ down-regulated E2F-1 and increased p21 (Cip1) and p27 (Kip1) expression. We demonstrated that TQ inhibited expression of anti-apoptotic proteins including IAP-1, survivin, and Bcl-2 and proliferative proteins including Cyclin D1. We also showed that TQ inhibited expression of proteins involved in invasion and metastasis including COX-2, VEGF, and MMP-9. Further, TQ significantly potentiated Gem effects in reduction of E2F-1 and anti-apoptotic proteins along with increase of p21 and p27. In a PANC-1 heterotopic xenograft model, TQ given daily orally (50 mg/kg) in combination with Gem (25 mg/kg intraperitoneally twice weekly) for 4 weeks significantly reduced tumor volume as compared to control vehicle, TQ alone, or Gem alone groups. We showed that in vivo suppression of tumor growth was associated with potent reduction in E2F-1, c-myc, and Cyclin D1 with concomitant increase in p21 and p27 expression in tumor explants. Furthermore, we demonstrated that TQ + Gem significantly reduced proliferation index (Ki-67+ cells) and increased apoptosis (in situ TUNEL assay) in tumor explants. Conclusion: Collectively, we showed that TQ potently potentiated cytotoxic effects of gemcitabine in PC cells both in vitro and in vivo. These effects could be in part due to downregulation of E2F-1, necessary for proliferation, survival, and chemo-resistance of PC.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2759.
Re: Lorenzo Marconi, Thomas Stonier, Rafael Tourinho-Barbosa, et al. Robot-assisted Radical Prostatectomy After Focal Therapy: Oncological, Functional Outcomes and Predictors of Recurrence. Eur Urol 2019;76:27–30
Authors: Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Francesco Montorsi, Rodolfo Montironi
Journal: European Urology (2019)
A phase II RCT of high-dose vitamin D supplementation and exercise for cancer treatment-induced bone loss in breast cancer patients on aromatase inhibitors.
Authors: Luke Joseph Peppone, Jennifer E Reschke, Michelle Christine Janelsins, Julia Ellen Inglis, Karen Michelle Mustian, Eva Culakova, Amber Kleckner, Charles Stewart Kamen, Po-Ju Lin, Richard Francis Dunne, Ian Kleckner, Alissa Huston, Michelle Shayne, Gary R. Morrow
Journal: Journal of Clinical Oncology (2019)

11500 Background: Cancer-treatment-induced bone loss (CTIBL) is a side effect of aromatase inhibitors (AIs) and can result in osteoporotic fractures. Vitamin D (VITD) protects against postmenopausal bone loss but it is unclear if the recommended daily allowance (RDA: 600 IU/day) of VITD is sufficient to prevent CTIBL. This phase II RCT aimed to assess the feasibility, safety, and preliminary efficacy of high-dose VITD (with and without exercise) on bone mineral density (BMD) compared to the RDA. Methods: Non-metastatic breast cancer patients starting AIs with low VITD (&lt;32 ng/ml) were randomized 1:1:1 into 3 arms: 1) placebo 2) high-dose VITD (50,000 IU/week) or 3) high-dose VITD + Exercise for Cancer Patients (EXCAP): a home-based, personalized walking and resistance band training program for 24 weeks. All subjects received the RDA of VITD 600 IU/day. Serum VITD and calcium levels were assessed at baseline, weeks 6, 12, 18, and 24. BMD was assessed at the hip via DXA at baseline and week 24. Results: Of the 116 subjects randomized (mean age = 60; 94% white; mean baseline VITD = 24.6 ng/mL), 90 provided fully evaluable data. Compliance (≥ 80% of instructed doses) exceeded 95% in all 3 arms with no between-group difference. ANCOVA showed significant differences between groups on final VITD levels (high-dose = 63.6 vs high-dose + EXCAP = 60.3 vs placebo = 32.0 ng/mL; p&lt;0.001) without severe calcium toxicities, as indicated by final calcium level (high-dose = 9.4 vs high-dose + EXCAP = 9.5 vs placebo = 9.4 ng/mL; p = 0.78). The placebo group lost a significant amount of hip BMD (−1.7%; p &lt; 0.01) while hip BMD was maintained in the high-dose (−0.1%; p = 0.77) and high-dose + EXCAP (−0.2%; p = 0.74) resulting in significant between-group differences for high-dose + EXCAP vs placebo (p = 0.04) and high-dose vs placebo (p = 0.05). Conclusions: This is one of the first studies to show our novel high-dose VITD intervention, with and without exercise, significantly reduced hip BMD loss in breast cancer patients on AIs. Moreover, high-dose VITD supplementation is safe and feasible in this population. A phase III RCT is needed to confirm these findings. Funding: K07CA168911. Clinical trial information: NCT01419730.
Abstract #4558: Histone deacetylase inhibitor induces autophagy through targeting mitochondria
Authors: Xiaobo cao, James Littlejohn, Daniel Jupiter, Lidong Zhang, Vincent Vanburen, Roy Smythe
Journal: Cancer Research (2009)

In this report, we demonstrate that HDAC inhibitors facilitate programmed cell death (apoptosis and autophagy) by disrupting mitochondrial membrane potential. We provide evidence that HDAC inhibitors selectively target mitochondria by repressing Bcl-xl transcription and reducing Akt phosphorylation. Elevated Tel, an Ets-transcriptional repressor, was required for the repression of Bcl-xl promoter activity. HDAC inhibitors reduced AKT kinase through disruption of HDAC-PP1 complexes. The combination of these effects resulted in decreased mitochondrial membrane potential followed by programmed cell death, both apoptosis and autophagy. In the tumor cells, we demonstrated that apoptosis and autophagy were mutually exclusive. Reducing Beclin-1 resulted in increased apoptotic cell death, while reducing bak and bax enriched the autophagic population. Nix, mitochondrial BH3-only protein, is required for the formation of mitophagy following HDAC inhibitor treatment. In a tumor cell line that is Nix-null (REN) and I-45 cells transfected with Nix siRNA, we observed no mitophagy. Taken together our results show that autophagy plays a protective role in the tumor cell during HDAC inhibitor based therapy.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4558.
<i>ICD</i>-<i>10</i> Coding of Type 2 Myocardial Infarction and Myocardial Injury as It Relates to US Centers for Medicare &amp; Medicaid Services Value-Based Payment Programs—Reply
Authors: Cian P. McCarthy, Sean T. McWalters, Jason H. Wasfy
Journal: JAMA Cardiology (2019)

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
Quantitative fluorescence inter-simple sequence repeat PCR (FISSR-PCR) for subclonal analysis of bronchial cell populations
Authors: Tao Lu, Walter N. Hittelman
Journal: Cancer Research (2004)

2925  Tumorigenesis is a process of cumulative clonal and subclonal cell expansion in a field of epithelial cells driven by genetic instability. Quantitative assessment of the frequency and complexity of clonality in pre-malignant tissues may therefore provide cancer risk information. Inter-Simple Sequence Repeat PCR (ISSR-PCR) is a DNA fingerprinting technology that has proven useful for quantifying clonal changes in human tumors. FISSR-PCR involves the same technology as ISSR-PCR except that fluorescence-dye labeled oligonucleotide primers are utilized and the PCR products are analyzed using the ABI 377 DNA Sequencer. We previously demonstrated that FISSR-PCR could distinguish clonal outgrowths of bronchial epithelial clones derived from single cells. The purpose of this study was to determine the sensitivity of FISSR-PCR to detect subclonal variation in populations of bronchial epithelial cells. To this end, DNA of single cell clones with gains and losses at known loci, previously isolated from lung epithelial Beas 2B and 1170I cell lines, were mixed together in different proportions at 10% increments to mimic cell populations with different degrees of subclonal variation. Following gel separation and fluorescence quantitation of size (i.e., migration) and relative amount (peak size) of the resultant PCR fragments, the DNA band profiles were aligned on the basis of the largest cluster of common bands. The scans derived from the various cell mixtures were then compared on the basis of normalized peak heights. For common peaks between variant cell populations, the standard deviation was found to be less than 10% of the absolute mean value (data from triplicates of 11 population mixture reactions). On the other hand, the relative peak height of known variant bands varied linearly with the relative ratio of cell mixtures (linear regression analysis, R2 >0.98). Based on these studies, a change in relative peak height of 20% was sufficient to detect the presence of a subclonal variant. This suggests that FISSR-PCR may provide a sensitive technique for quantifying clonal variation in bronchial epithelial cell populations and may prove useful for cancer risk assessment. Supported in part by DAMD17-02-1-0706, CA-68437, and CA70907.
Characterization of a novel non-classical CD4+ clone with broad reactivity against human renal cell carcinomas (RCCs)
Authors: Jens Dannull, Hubert R. Kuebler, Timothy T. Tseng, Aijing Zhang, Zhen Su, Philipp Dahm, Johannes Vieweg
Journal: Cancer Research (2006)

3866  Introduction: Renal cell cancer affects the immunsystem by inhibiting the process of differentiation of antigen-resenting cells from their myeloid precursors by secreting tumor-derived factors such as VEGF. Immature myeloid cells (ImC) induce a profound state of immune suppression that foster tumor tolerance by inhibition of tumor specific T cells. In this study, we asked whether increased ImC frequencies can be found in peripheral blood from RCC patients and if ImC frequencies correlated positively with increased levels of tumor-derived serum markers. Methods: ImC frequencies in peripheral blood from healthy volunteers and RCC patients were determined by FACS. ImC were isolated by magnetic bead separation techniques and their immunosuppressive activity was determined in CTL assays, IFN-γ ELISPOT analyses and T-cell proliferation assays. The production of reactive oxygen species by ImC was analyzed utilizing specific probes and inhibitors. Tumor-derived serum markers were quantified by ELISA, enzyme immune assays and cytometric bead arrays. Microarray analyses were performed to identify novel and highly specific ImC markers. Results: RCC patients demonstrate higher ImC frequencies (0.8 - 3.2 % of total PBMC) compared to healthy donors. The increased ImC frequencies are positively correlated with serum levels of VEGF, PGE-2, IL-13 and M-CSF in RCC patients and the concentration of byproducts of oxidative burst, including iso-prostane and malondialdehyde, was significantly enhanced. Isolated ImC exhibited profound immunosuppressive effects on CTL and CD4+ T cell response in an antigen specific fashion. Immunosuppression by ImC was mediated by release of ROS, including peroxide and superoxide anions and by generation of nitric oxide radicals as evidenced in functional assays. Results from microarray analyses reveal EP-1, EphA5, and PEX-5 as novel ImC markers. Conclusions: These data suggest that RCC may induce the development of immunosuppressive ImC population through secretion of cytokines such as VEGF, IL-13, M-CSF and PGE-2. Inhibition of specific cytokine activity or the use of differentiating agents may represent strategies to decrease immunosuppressive ImC population. Results from a phase I clinical trial investigating the effects of all-trans retinoic acid (ATRA) on differentiation of ImC in RCC patients will be presented.
Apolipoprotein A‐IV acts as an endogenous anti‐inflammatory protein and is reduced in treatment‐naïve allergic patients and allergen‐challenged mice
Authors: David Roula, Anna Theiler, Petra Luschnig, Gunter J. Sturm, Peter V. Tomazic, Gunther Marsche, Akos Heinemann, Eva M. Sturm
Journal: Allergy (2019)

Abstract Background Recent studies pointed to a crucial role for apolipoproteins in the pathogenesis of inflammatory diseases. However, the role of apolipoprotein‐IV (ApoA‐IV) in allergic inflammation has not been addressed thoroughly thus far. Objective Here, we explored the anti‐inflammatory effects and underlying signaling pathways of ApoA‐IV on eosinophil effector function in vitro and in vivo. Methods Migratory responsiveness, Ca 2+ ‐flux and apoptosis of human peripheral blood eosinophils were assessed in vitro. Allergen‐driven airway inflammation was assessed in a mouse model of acute house dust mite‐induced asthma. ApoA‐IV serum levels were determined by ELISA. Results Recombinant ApoA‐IV potently inhibited eosinophil responsiveness in vitro as measured by Ca 2+ ‐flux, shape change, integrin (CD11b) expression, and chemotaxis. The underlying molecular mechanism involved the activation of Rev‐ErbA‐α and induced a PI3K/PDK1/PKA‐dependent signaling cascade. Systemic application of ApoA‐IV prevented airway hyperresponsiveness (AHR) and airway eosinophilia in mice following allergen challenge. ApoA‐IV levels were decreased in serum from allergic patients compared to healthy controls. Conclusion Our data suggest that ApoA‐IV is an endogenous anti‐inflammatory protein that potently suppresses effector cell functions in eosinophils. Thus, exogenously applied ApoA‐IV may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophil‐driven disorders.
Phase I dose-escalation study of oral vinorelbine (VRLO) plus pemetrexed (PEM) in patients (pts) with advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC).
Authors: Marta Isabel Sierra, Raquel Losa, Maria Tresguerres, Eduardo Gutierrez Restrepo, Quionia Perez, Carlos Alvarez, Jose Pablo Berros, Noemi Villanueva, Jose Manuel Gracia, Emilio Esteban
Journal: Journal of Clinical Oncology (2012)

e18044 Background: PEM and VRLO have shown high activity and good safety profile when given as single agent chemotherapy for NSCLC. Platinum combinations are considered the standard of care of first-line advanced NSCLC treatment. However, some patients cannot receive platinum salts, being treated with non-platinum combinations as an alternative treatment option. PEM is indicated for the 1 st -line treatment of patients with locally advanced or metastatic NSCLC other than predominantly squamous cell histology. VRLO is indicated for stage III-IV NSCLC and has shown efficacy in all histology subgroups. Their combination could offer a treatment option in non-squamous 1st-line NSCLC. Methods: A phase I study is being conducted to determine the maximal tolerated dose (MTD) of PEM on day 1 plus VRLO given on days 1 and 8, with 3-weeks cycles as 1st-line treatment in locally advanced or metastatic non-squamous NSCLC pts. Results: As of Jan-2012, 18 pts (M/F: 13/5, median age 61, all PS 0-1) had received 104 cycles in 4 dose levels (DL): VRLO (mg/m 2 )/PEM (mg/m 2 ): 60/500 (5 pts, DL1), 70/500 (7 pts, DL2), 60-80/500 (3 pts, DL3), 80/500 (3 pt-DL4). Safety: dose limiting toxicity as defined per protocol was neutropenia gr 4 with febrile neutropenia at DL2. Other toxicities were: neutropenia gr 3 (3 pts), gr 2 (2 pts); leukopenia gr 2 (3 pts). Other adverse events included: vomiting (gr 3 / 1 pt) (gr 2 / 5 pts); gr 2 asthenia (5 pts); constipation (gr 2 / 1 pt) (gr 1 / 2 pts); diarrhea (gr 1 /3 pts); fever (gr 1/1 pt); alopecia (gr 1/ 1 pt). Efficacy in 15 evaluable pts: CR, 0 pts; PR, 9 pts; NC, 3 pts; PD, 2 pts. Overall response rate, 60% (73% clinical benefit). Conclusions: The administration of PEM plus VRLO is feasible, the MTD being reached at 80/500 mg/m 2 . Further exploration of the combination will be planned after final analysis.
A Broad Impact for Global Oncology
Authors: C. Norman Coleman, Eugenia (Nina) Wendling, David A. Pistenmaa
Journal: JAMA Oncology (2019)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
Angiogenesis in early stages of hepatoma development from carcinogen induced rat hepatocarcinogenesis model.
Authors: Phyllis M. Novikoff, Pallavi Annamaneni, Mark T. Bielawski
Journal: Cancer Research (2004)

3597   Angiogenesis is essential for hepatoma growth and metastasis and is prominent at later stages of hepatocarcinogenesis. To investigate whether angiogenesis may be associated with early premalignant stages, we studied this process in the Solt-Farber animal model protocol (Solt et al. Am J Path, 1977) at early stages (altered foci and hyperplastic preneoplastic nodules) by in situ methods and cDNA microarray technology. The protocol produces sequential stages of foci, hyperplastic preneoplastic nodules (PN), neoplastic nodules and hepatomas at predictable times during carcinogenesis with metastasis of hepatoma cells to the lungs. Male Fischer 344 rats were treated with carcinogens, diethylnitrosamine (DEN) for two weeks, followed by acetylaminofluorene (AAF) for two weeks and surgical two-thirds partial hepatectomy (PH) one week after AAF. Livers were removed from rats under anesthesia 3 and 9 days after PH. Liver slices (1–2 mm) were cut and fixed by immersion and frozen liver sections (10-20 μm) prepared for in situ analysis. Total RNA was isolated from PN tissue, amplified and hybridized to a 27K mouse chip. To determine the vascular network in liver sections at the foci and PN stages (3 and 9 days after PH, respectively), enzyme cytochemistry and immunocytochemistry were used to localize ATPase activity, actin or von Willebrand factor (vWF) in vessels and endothelial cells. Bright field and confocal microscopy (for multiple fluorescent labels) were used to visualize the localizations. We found extensive development of a vascular network coursing through the parenchymal liver tissue surrounding the PN at 9 days after PH; at this time multiple PN are present in the liver. A less extensive vascular network was present within the PN. Blood vessels extend from portal triad regions as tortuous profiles to the periphery of PN, encircling them. Vessels also projected into the PN forming smaller branches within nodules. Vascular networks surrounded all PN within the liver section. The vascular network was closely associated with the proliferated bile ductule (BD) system that develops with the protocol. The BD system extended from the portal areas to one pole of the PN and appeared to contact the PN surface. Preliminary studies on cDNA microarray analysis of amplified RNA isolated from PN tissue showed several up-regulated genes encoding proteins that function in angiogenesis. These results indicate that at the PN stage, neovascularization due to either angiogenesis or endothelial precursor cells or both occurs before the appearance of neoplastic nodules and hepatomas. The increased vascular microenvironment at an early stage of liver cancer presumably contributes to growth of PN and possibly transformation of PN from a premalignant to a malignant state. Supported in part by NIH CA06756.