tbuckley/cabot-search huggingface dataset:
Beckwith-Wiedemann Syndrome Negligible Effects on Tumor Risk Associated With In Vitro Fertilization
Authors: Diana Carli, Giovanni Battista Ferrero, Alessandro Mussa
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Advances in the Management of Platinum-Sensitive Relapsed Ovarian Cancer
Authors: Sara Bouberhan, Eric Pujade-Lauraine, Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2019)

Article Tools REVIEW ARTICLES Gynecologic Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.19.00314 Journal of Clinical Oncology - published online before print August 12, 2019 PMID: 31403861 Advances in the Management of Platinum-Sensitive Relapsed Ovarian Cancer Sara Bouberhan, MD1xSara BouberhanSearch for articles by this author; Eric Pujade-Lauraine, PhD, MD2xEric Pujade-LauraineSearch for articles by this author; and Stephen A. Cannistra, MD1xStephen A. CannistraSearch for articles by this author Show More 1Beth Israel Medical Center and Harvard Medical School, Boston, MA2Association of Research on Cancers Including Gynecological–Group of National Investigators for the Study of Ovarian Cancer and Breast, Paris, France https://doi.org/10.1200/JCO.19.00314 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology
Abstract #4635: Polyethylenimines (PEIs) and PEI derivatives for the in vivo application of siRNA and shRNA: therapeutic efficacies of RNAi in various tumor models
Authors: Sabrina Höbel, Melanie Günther, Anastasia Malek, Miriam Jenß, Bettina Bartel, Marius Grzelinski, Frank Czubayko, Achim Aigner
Journal: Cancer Research (2009)

The efficient delivery of siRNAs or shRNA-encoding DNA plasmids in vivo is an essential prerequisite for the therapeutic application of RNA interference (RNAi). Polyethylenimines (PEIs) are water-soluble synthetic polymers with protonable amino groups which are able to form non-covalent complexes with DNA and siRNAs, mediating their protection against nucleolytic degradation as well as cellular uptake and intracellular release. Here we show the therapeutic efficacy of PEI/shRNA- or PEI/siRNA-mediated RNAi in various mouse tumor models upon systemic treatment. The intraperitoneal (i.p.) administration of shRNA constructs targeting HMGA2 reduced or abrogated the growth of subcutaneous (s.c.) or i.p. ovarian carcinoma xenografts, respectively. Anti-tumor efficacies of PEI/siRNA-mediated gene knockdown were evaluated in s.c. prostate or pancreatic xenografts for VEGF knockdown. The comparison of (i) PEI/siRNA-mediated targeting of the growth factor VEGF, (ii) treatment with the therapeutic anti-VEGF antibody Avastin and (iii) a combination of both revealed, dependent on the tumor model, comparable or additive anti-tumor effects. Critical for in vivo siRNA delivery are the PEIs or PEI derivatives being used. The recently introduced low molecular weight PEI F25-LMW demonstrated favorable features regarding the long-term storage of the complexes, the absence of side effects in mice, and high therapeutic efficacy. Furthermore the grafting of PEI with poly(ethylene glycol) (PEG) markedly alters PEI complexes with regard to physicochemical properties, biological activity and biocompatibility. We show, however, that in contrast to DNA transfection efficacies, siRNA-mediated gene targeting in vitro is much less dependent on the PEGylation of PEI. In vivo, biodistribution studies reveal distinct siRNA delivery profiles being dependent on the route of injection and the degree and pattern of PEGylation. The induction of erythrocyte aggregation and hemorrhage in the lung upon i.v. injection, which is dependent on the N/P ratio in the complex, are critical parameters. Furthermore, in liver and spleen, but not in lung and kidney, siRNA levels are dependent on macrophage activity. Thus, a panel of certain modified or non-modified low-molecular weight PEIs are promising candidates for therapeutic siRNA-mediated gene targeting and represent a powerful delivery platform for the application of siRNAs in anti-tumor treatment.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4635.
Novel H2S-Releasing hydrogel for wound repair via in situ polarization of M2 macrophages
Authors: Jiang Wu, Anqi Chen, Yajiao Zhou, Sen Zheng, Yao Yang, Ying An, Ke Xu, Huacheng He, Jianming Kang, Jittima Amie Luckanagul, Ming Xian, Jian Xiao, Qian Wang
Journal: Biomaterials (2019)
Identification of Molecular Markers of Tumor Cell Sensitivity and Resistance to Natural Killer Cells through Genome-Wide CRISPR Activation and CRISPR Editing Screens in Multiple Myeloma Cell Lines: Implications for Anti-Myeloma Immunotherapy
Authors: Sara Gandolfi, Michal Sheffer, Emily Lowry, Olga Dashevsky, Ryosuke Shirasaki, Ricardo De Matos Simoes, Constantine S. Mitsiades
Journal: Blood (2018)
ABT-510, a modified type 1 repeat peptide of thrombospondin, inhibits malignant glioma growth in vivo by inhibiting angiogenesis
Authors: Joshua Anderson, Robert Grammer, Wenquan Wang, L. Burton Nabors, Jerry Stewart, Candece Gladson
Journal: Cancer Research (2007)

4647  Anti-angiogenic therapies would be particularly beneficial in the treatment of malignant gliomas. Peptides derived from the second type 1 repeat (TSR) of thrombospondin-1 (TSP-1) have been shown to inhibit angiogenesis in non-glioma tumor models and a modified TSR peptide, ABT-510, has now entered into Phase II clinical trials of its efficacy in non-glioma tumors.As microvascular endothelial cells (MvEC) exhibit heterogeneity, we evaluated the ability of the modified TSR peptide (NAcSarGlyValDalloIleThrNvaIleArgProNHE, ABT-510) to inhibit malignant glioma growth in vivo and to induce apoptosis of brain microvessel endothelial cells (MvEC) propagated in vitro. We found that daily administration of ABT-510 until euthanasia (days 7 to 19), inhibited the growth of human malignant astrocytoma tumors established in the brain of athymic nude mice. The microvessel density was significantly lower and the number of apoptotic MvEC was significantly higher (3-fold) in the tumors of the ABT-510-treated animals. Similar results were found using a model in which the established tumor is an intracerebral malignant glioma propagated in a syngeneic mouse model. ABT-510 treatment of primary human brain MvEC propagated as a monolayer resulted in induction of apoptosis in a dose- and time-dependent manner through a caspase-8-dependent mechanism. It also inhibited tubular morphogenesis of MvEC propagated in collagen gels in a dose- and caspase-8 dependent manner through a mechanism that is blocked by antibody against the TSP-1 receptor (CD36) on the MvEC. These findings indicate that ABT-510 should be evaluated as a therapeutic option for patients with malignant glioma.
Double akylating agents treatment with ifosfamide (IFOS) and cyclophosphamide (CYCLO) for relapsed pediatric solid tumors.
Authors: Sidnei Epelman, Ethel Gorender, Annick Beaugrand, Renato Melaragno, Priscila Meirelles, Renato Guedes Oliveira
Journal: Journal of Clinical Oncology (2013)

10057 Background: CYCLO and IFOS are two of the most active agents in childhood cancer. There is non-cross resistance between CYCLO and IFOS and they have dissimilar toxic side effects. In vitro, tumor model systems document that alkylator resistance may be overcome by several fold increases in drug concentration. We developed a strategy in attempt to limit side effects and increase anticancer activity of high doses oxazaphosphorines therapy: an association of IFOS plus CYCLO, giving an equivalent to 20g/m 2 of IFOS or 5g/m 2 of CYCLO. The schedule is the association of these two drugs: CYCLO 2,5g/m 2 (corresponding to 10g/m 2 of IFOS) plus IFOS 10g/m 2 . Methods: Eligibility included recurrent/refractory measurable disease, life expectancy &gt; 6 weeks, adequate renal, hepatic and bone marrow function. CYCLO (2,5g/m 2 ) and IFOS (10g/m 2 ) with Mesna, with interval of 21 days. Responses were evaluated after 2 cycles.So far, 13 patients were enrolled: median age 17 years (5-26), 9M:4F,6 osteosarcoma, 1 hemangioperycitoma, 2 medulloblastoma, 1 nasopharyngeal carcinoma, 1 Wilms tumor,1 synoviosarcoma, 1 retinoblastoma. Six patients received IFOS previously (Total= 38 - 63 g/m²) and 5 CYCLO. Results: Thirty four cycles were evaluated. Toxicity was tolerable with no death. Main adverse event was neutropenia grade (GR) 4 in all cycles, median duration of seven days (3-15), GCS-F was used in all cycles; anemia GR 3 and 4 and thrombocytopenia GR 4 in 14 cycles; infection GR 3 and 4 in 15 cycles; hemorrhage cystitis GR 1 in 2 cycles and neurologic toxicity GR 2 in 6 cycles. No acute renal toxicity was observed. Responses were 2 complete response (CR), 5 partial responses (PR), 3 stable disease, and 3 progress disease. Conclusions: This schedule is feasible with high response rate (CR+PR=54%). Due to lack of new agents, innovative approaches for high risk patients can have a potential benefit. More patients are warranted.
Neutrophil Extracellular Traps Initiate Gallstone Formation
Authors: Luis E. Muñoz, Sebastian Boeltz, Rostyslav Bilyy, Christine Schauer, Aparna Mahajan, Navena Widulin, Anika Grüneboom, Irmgard Herrmann, Edgyda Boada, Manfred Rauh, Veit Krenn, Mona H.C. Biermann, Malgorzata J. Podolska, Jonas Hahn, Jasmin Knopf, Christian Maueröder, Solomiya Paryzhak, Tetiana Dumych, Yi Zhao, Markus F. Neurath, Markus H. Hoffmann, Tobias A. Fuchs, Moritz Leppkes, Georg Schett, Martin Herrmann
Journal: Immunity (2019)
Higher incidence of single nucleotide polymorphisms at codon 72 of the p53 gene are associated with poor prognosis of African-American patients with high grade colorectal adenocarcinomas
Authors: Rahul R. Goli, Venkat R. Katkoori, Tom Callens, Ludwine Messiaen, Nirag C. Jhala, William E. Grizzle, Upender Manne
Journal: Cancer Research (2006)

391  Background: We reported an increased incidence of mortality for African-Americans with colonic adenocarcinomas but not with rectal adenocarcinomas when compared to Caucasians (Cancer 2004;101:66-76); moreover, this disparity was due to high-grade CRCs (Cancer 2005;103:2163-70). To understand the molecular basis for this disparity, the current preliminary study assessed the mutational patterns of the p53 gene and microsatellite instability (MSI) in high-grade CRCs collected from African-American and non-Hispanic Caucasian patients and correlated with their survival. Materials and Methods: The genomic DNA samples were isolated from archival tissues of high-grade CRCs and matching control tissues collected from 27 African-American and 32 Caucasian patients. None of these patients have received any pre- or post-surgery adjuvant therapies. The status of the p53 gene was assessed by direct sequencing of the entire coding region (exons 2 through 11), using exon-specific primers. Polymerase chain reaction amplifications were performed with the National Cancer Institute-recommended 5-oligonucleotide primer sets to assess the BAT25, BAT26, D2S123, D5S346 and D17S250 loci. We used the Chi-square test to compare baseline characteristics and Univariate Kaplan-Meier survival analyses to assess the prognostic significance of molecular alterations based on race/ethnicity. Results: Similar proportions of high-grade CRCs from African-American and Caucasian patients have exhibited the high-level MSI (MSI-H) (37% versus 41%) and missense point mutations at hotspot codons 175, 245, 248, 273, or 282 of the p53 gene (11% versus 16%). In contrast, single nucleotide polymorphic mutations (SNP) at codon 72 (Arginine to Proline) were more frequent in African-Americans (33%) than in Caucasians (9%) (χ2, P = 0.025). African-Americans with SNPs at codon 72 which exhibit the phenotypes, Proline/Proline (33%) or Arginine/Proline (37%) had higher mortality than those with the phenotype Arginine/Arginine (30%) (Overall, log-rank, P=0.023), such a difference in mortality was not observed in Caucasian patients (Overall, log-rank, P=0.630). Conclusions: These preliminary findings suggest that the SNP pattern at codon 72 of the p53 gene differs in African-American and Caucasian patients with high-grade CRCs; specifically, the phenotypes Arg/Pro or Pro/Pro of p53 are associated with poor clinical outcome of African-American patients. These studies are supported by a NCI/NIH grant CA098932-01.
ERBB4/4ICD a novel BH3-only protein and estrogen receptor coactivator regulates tamoxifen induced apoptosis of breast tumor cells
Authors: Anjali Naresh, Frank Jones
Journal: Cancer Research (2007)

3630  ERBB4 is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e., EGFR, ERBB2, and ERBB3), which are associated with aggressive forms of human cancers, ERBB4 expression seems to be selectively lost in tumors with aggressive phenotypes. Consistent with this observation, we have shown that ERBB4 induces apoptosis when reintroduced into breast cancer cell lines or when endogenous ERBB4 is activated by a ligand. Upon ligand activation, membrane ERBB4 undergoes proteolytic processing to release the ERBB4 intracellular domain (4ICD). We show that cleavage of endogenous ERBB4 is critical for ERBB4 apoptotic activity and results in mitochondrial accumulation of the 4ICD followed by cytochrome c efflux and activation of cellular caspases. We further show that 4ICD harbors a functional BH3 domain and ERBB4 functions as a unique proapoptotic member of BCL-2 family. Clinically, cytosolic but not membrane ERBB4/4ICD expression in primary human breast tumors was associated with tumor apoptosis, providing a mechanistic explanation for the loss of ERBB4 expression during tumor progression. Alternatively, we have shown that ERBB4/4ICD is a transcriptional coactivator and 4ICD directly interacts with estrogen receptor (ER) to selectively potentiate estrogen regulated gene expression. Furthermore ERBB4 itself is an estrogen regulated gene and 4ICD contributes to estrogen-induced proliferation of ER positive breast cancer cells. These observations are corroborated clinically where ERBB4 is significantly associated with ER expression in primary breast tumors. Strikingly, the vast majority of patients with tumors coexpressing ERBB4 and ER respond to endocrine therapy whereas 40% of patients expressing ER alone succumb to their disease. Based upon these clinical results we tested the hypothesis that ERBB4 regulates tumor response to endocrine therapy. In support of this hypothesis we found that in three independent preclinical cell models, tamoxifen resistance was associated with the suppression of ERBB4 expression. Furthermore, reintroduction of ERBB4 in a tamoxifen resistant cell line reestablished tamoxifen sensitivity. Tamoxifen treatment of breast cancer cells resulted in translocation of the 4ICD BH3-only protein to the mitochondria and activation of apoptosis. The molecualr mechanisms underlying this unique mode of action for tamoxifen will be described. We propose that ERBB4 represents an important tumor marker predicting therapeutic response of breast cancer patients undergoing endocrine therapy.
Prostate-specific deletion of Apc leads to early onset prostate cancer
Authors: Troy A. Giambernardi, Holli M. Charbonneau, Jose Toro, J. C. Goolsby, James H. Resau, Pradip Roy-Burman, Aubie Shaw, Wade Bushman, Bart O. Williams
Journal: Cancer Research (2005)

1960  Prostate cancer causes over 42,000 deaths per year in the United States. Most deaths are due to the metastatic spread of prostate cancer throughout the body. Currently, the only effective therapy for advanced prostate cancer is androgen depletion by surgical or chemical castration. This often causes temporary remission of the tumor. Unfortunately, prostate cancer commonly recurs in these patients in a form that is androgen-independent. There is currently no effective treatment for androgen independent prostate cancer and there is an urgent need to develop effective therapies for this disease. β-catenin plays multiple roles in regulating cell growth and function. Normally, the cytoplasmic levels and nuclear localization of β-catenin is tightly regulated. In many tumors, however, this regulation is lost, either due directly to mutations in the β-catenin gene or by mutations in genes whose protein products are necessary for this regulatory process. One example is colon cancer, where the vast majority of tumors display increased cytoplasmic levels and nuclear localization of β-catenin due to loss of the APC gene. The majority of advanced prostate tumors have elevated levels of β-catenin, and mutations in the β-catenin gene have been identified in prostate tumors. β-catenin can specifically associate with the androgen receptor (AR). This interaction alters the signaling capabilities of the AR, making it more promiscuous in its ability to be activated by steroid hormones other than androgens. Based on these observations, β-catenin activation represents is a viable target for therapeutic intervention in advanced prostate cancers. We are pursuing experiments to address the effect of inappropriate activation of β-catenin in the prostate. We have created mice carrying a prostate-specific deletion in the Apc gene and found that such mice develop early onset prostate cancer. Hyperplastic changes are evident as early as five weeks of age, and evidence of carcinoma is present in all animals older than four months examined to date. Preliminary work suggests that the tumors regress after androgen ablation. Ongoing work is aimed at assessing the ability of these tumors to metastasize, and to determine how loss of Apc interacts with other mutations associated with prostate cancer to affect tumor progression.
Oxidative stress induction of L1 cell adhesion molecule expression promoted androgen-independent prostate cancer cell survival: A potential therapeutic application in radiation therapy
Authors: Ira Rajbhandari, Shian-Ying Sung, Nicole Johnson, Rebecca Arnold, John Petros, Peter Johnstone, Chia-Ling Hsieh
Journal: Cancer Research (2007)

4861  Hormone refractory prostate cancer cells frequently relapses from therapy and inevitably progresses to bone-metastatic status with no cure. However, the molecular mechanisms underlying this event are poorly understood. Biological functions of cell adhesion molecules have been implicated as a critical regulator for cancer resistance to cytotoxic stress. We previously showed that L1 cell adhesion molecule (L1CAM) is expressed by androgen-independent prostate cancer cell lines with a positive correlation to metastasis potential, and that mean serum L1CAM levels are significantly higher in patients with bone metastases than in those with organ-confined tumors or normal controls. For this communication we further investigate the role of L1CAM in prostate cancer survival at adverse microenvironment. We found that the survival of androgen-independent PC3 cells with genetically modulated L1CAM overexpression was significantly higher than that of parental or vector control line under several stressed conditions, including nutrient depletion, oxidative stress and radiation treatment using MTS cell proliferation assay and clonogenic analysis. Conversely, downregulation of L1CAM in PC3 cells using L1CAM-targeting siRNA markedly increased cell death from H2O2 treatment, as determined by using a Cell Live/Death Staining kit as well as Annexin V and cell cycle analysis, indicating L1CAM involvement in the cellular response to stress. Moreover, while the L1CAM signal elevates the intracellular H2O2 level and expression of reactive oxygen species (ROS)-generating NAD(P)H oxidases 1 (Nox1) and ROS-target genes, including c-Myc and MMP-2, environmental oxidative stress such as H2O2, ionizing radiation and the oxidative stress related to cytokine TGF-β could also influence L1CAM protein expression, indicating activation of the ROS pathway occurs downstream of L1CAM signaling and may confer therapeutic resistance in hormone-refractory prostate cancer. Taken together, the present study demonstrated a novel function of L1CAM in prostate cancer cell survival in vitro in response to oxidative stress and radiation. Exploring the links between ROS, radiation, stress signaling and L1CAM may help us understand the molecular mechanism of stress-induced prostate cancer progression and devise better radiation strategies for bone metastasis.
Neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with oestrogen receptor-positive, HER2-negative, early-stage breast cancer (LORELEI): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Cristina Saura, Dominik Hlauschek, Mafalda Oliveira, Dimitrios Zardavas, Anita Jallitsch-Halper, Lorena de la Peña, Paolo Nuciforo, Alberto Ballestrero, Peter Dubsky, Janine M Lombard, Peter Vuylsteke, Carlos A Castaneda, Marco Colleoni, Giuliano Santos Borges, Eva Ciruelos, Monica Fornier, Katalin Boer, Aditya Bardia, Timothy R Wilson, Thomas J Stout, Jerry Y Hsu, Yi Shi, Martine Piccart, Michael Gnant, José Baselga, Evandro de Azambuja
Journal: The Lancet Oncology (2019)
SAT0242 Anakinra increases days of work and domestic activity in patients with rheumatoid arthritis
Authors: B Bresnihan, WW Chan, JM Woolley
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the effect of anakinra treatment on days of work and domestic activity in patients with rheumatoid arthritis (RA). <h3>Methods</h3> In a six-month, placebo-controlled study conducted in Europe, 473 patients with RA were randomised to receive anakinra 30, 75 or 150 mg/day or placebo. Days of work and domestic activity were evaluated at baseline and after 4, 8, 12, 16, 20, and 24 weeks of therapy using an economic resource survey. The total days of work and domestic activity gained after commencing treatment were quantified as productivity and compared in patients receiving placebo or anakinra. <h3>Results</h3> Patients receiving anakinra demonstrated greater gains in productivity for all doses examined (see table). These gains occurred rapidly, with over a two-day gain by week 8, and over 13 days gained on completion of the study. Furthermore, at the end of the study, an additional 14% of patients receiving anakinra did not miss any work or domestic activity, compared to 6% receiving placebo (data not shown) Table 1. Productivity (Work and Domestic Activity) Days Gained: <h3>Conclusion</h3> Patients receiving anakinra treatment experienced rapid and dose-related increases in days of work and domestic activity.