tbuckley/cabot-search huggingface dataset:
Abstract P1-05-04: A novel mechanism of epithelial-mesenchymal transition in breast cancer metastasis: Involvement of prostanoid receptor
Authors: A Kwong, MT Siu, I Cheuk, JC Ho, J Chen, VY Shin
Journal: Cancer Research (2016)

Abstract Background: Triple-negative breast cancer is associated with higher metastatic rate and poor prognosis than other subtypes of breast cancer due to lack of targeted therapy. Epithelial-mesenchymal transition (EMT) is linked with metastasis with phenotypic conversion of epithelial cells. However, the regulation of EMT in breast cancer metastasis remains largely unstudied. Recent attention has focused on targeting the downstream of COX-2 pathway, understanding the role of prostanoid receptors in breast cancer metastasis may help the development of effective therapeutic interventions for patients with metastasis. Methods: A stable EP2-expression cell line (MB-231-EP2) was used to study tumorigenesis and distant metastasis in human breast cancer metastatic model. Localization of EP2 and EMT markers were examined by immunostaining and immunofluorescence. Profiles of drug transporters genes were compared between siEP2 and siControl cells. Functional role of EP2 on cell proliferation, invasion and apoptosis were assessed. Alteration of EMT markers were examined by real-time PCR and Western blot analysis. Results: Expression of EP2 receptor were higher in human primary tumors than non-tumor tissues. EP2 receptor was predominantly expressed in metastatic tumors than primary tumors in human breast cancer metastatic mice model. The metastatic tumors showed a higher Ki67 (cell proliferation) and CD31 (angiogenesis) than primary tumors in the xenograft tissues. Larger tumors and poor survival were seen in MD-231-EP2 bearing mice when compared with control. Silencing of EP2 by siRNA markedly reduced cell proliferation and invasion, but increased apoptosis and expression of solute carrier family 19 member A3 (SLC19A3) gene. Interestingly, SLC19A3 had a lower expression in primary tumors and was inversely correlated with EP2 expression. Ectopic expression of SLC19A3 suppressed cell proliferation and invasion through the restoration of E-cadherin and other EMT markers (Twist, Zeb1 and Snai2). Immunofluorescence staining showed that the localization of Twist and E-cadherin were altered in siEP2 cells. Conclusion: Our results showed that EP2 promoted EMT and breast cancer metastasis through the downregulation of SLC19A3 expression. Taken together, targeting EP2/SLC19A3 signaling pathway maybe a potential treatment for metastasis and adjuvant chemotherapy to reduce the metastatic risk. Citation Format: Kwong A, Siu MT, Cheuk I, Ho JC, Chen J, Shin VY. A novel mechanism of epithelial-mesenchymal transition in breast cancer metastasis: Involvement of prostanoid receptor. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-05-04.
Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis
Authors: Bo Wang, Kevin Yao, Brooke M Huuskes, Hsin-Hui Shen, Junli Zhuang, Catherine Godson, Eoin P Brennan, Jennifer L Wilkinson-Berka, Andrea F Wise, Sharon D Ricardo
Journal: Molecular Therapy (2016)

The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR-let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated kidney injury and significantly downregulated collagen IVα1, metalloproteinase-9, transforming growth factor (TGF)-β1, and TGF-β type 1 receptor (TGF-βR1) in UUO kidneys, compared with controls. In vitro analysis confirmed that the transfer of miR-let7c from miR-let7c-MSCs occurred via secreted exosomal uptake, visualized in NRK52E cells using cyc3-labeled pre-miRNA-transfected MSCs with/without the exosomal inhibitor, GW4869. The upregulated expression of fibrotic genes in NRK52E cells induced by TGF-β1 was repressed following the addition of isolated exosomes or indirect coculture of miR-let7c-MSCs, compared with NTC-MSCs. Furthermore, the cotransfection of NRK52E cells using the 3'UTR of TGF-βR1 confirmed that miR-let7c attenuates TGF-β1-driven TGF-βR1 gene expression. Taken together, the effective antifibrotic function of engineered MSCs is able to selectively transfer miR-let7c to damaged kidney cells and will pave the way for the use of MSCs for therapeutic delivery of miRNA targeted at kidney disease.
Abstract P1-03-06: Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity
Authors: C Giordano, S Panza, F Chemi, I Barone, D Bonofiglio, A Cordella, A Hashim, B Györffy, BM Simões, RB Clarke, A Weisz, S Catalano, S Andò
Journal: Cancer Research (2016)

Abstract Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and resistance to anticancer therapies. These cells rely for their properties on complex interactions with the tumor microenvironment through networks of cytokines and growth factors. In this study, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using breast cancer cell lines and patient-derived samples. We found that conditioned media (CM) from cancer associated fibroblasts and breast adipocytes significantly increase mammosphere formation in breast cancer cells. Depletion of leptin from stromal cell-CM as well as inhibition of leptin signaling by using a full leptin receptor antagonist peptide LDFI completely abrogated this effect. Accordingly, mammosphere cultures exhibited increased leptin receptor expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology in mammosphere cells treated with stromal cell-CM and leptin. Interestingly, leptin is able to increase the mammosphere formation in metastatic breast cancer cells isolated from patients (n = 10) and this can be blocked by using peptide LDFI. In addition, leptin receptor (OBR) mRNA expression, analyzed in cells from metastatic fluids, directly correlated with mammosphere formation activity ex vivo (r=0.68, p= 0.05; n = 8). Finally, Kaplan–Meier survival curves indicated that OBR expression correlated with reduced overall survival in breast carcinomas (HR=1.9, p=0.022). Together, our results suggest that leptin/leptin receptor may represent a potential therapeutic target that can block the stromal-tumor interactions that drive BCSC-mediated disease progression. Citation Format: Giordano C, Panza S, Chemi F, Barone I, Bonofiglio D, Cordella A, Hashim A, Györffy B, Simões BM, Clarke RB, Weisz A, Catalano S, Andò S. Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-03-06.
Editorial
Authors: PAUL D. WHITE
Journal: Circulation (1965)

excellent historical editorial "Nomen- clature and Criteria for the Diagnosis of Car- diovascular Diseases" in the September issue of Circulation, it occurred to me that as ail early worker in the field before 1920, I can supply information from my own experience, especially in Boston, which can amplify Dr. Kossmann's historical account.Before 1900 almost all discussions and writings about heart disease were concerned primarily and often solely with structural ab- normalities such as valvular deformities, en- largement of the heart chambers, pericarditis, and congenital deformities.At the turn of the century James Mackenzie and Karl Wenckebach, both of whom I myself observed in ac- tion, the former in the second decade of the century and the latter in the third, introduced the category of disorders of cardiovascular function to be added to that of structural
Abstract B49: Histone H3K27 tri-methylation regulates DPYD expression and cellular sensitivity of 5-fluorouracil
Authors: Rentian Wu, Steven Offer, Calvin Jerde, Garrett Dunlap, Robert Diasio
Journal: Cancer Research (2016)

Abstract Dihydropyrimidine dehydrogenase (DPD) is a major determinant of the efficacy and toxicity of 5-fluorouracil in various cancer therapies. Single nucleotide polymorphisms (SNPs) within DPYD have been studied extensively for years. However, known SNPs do not explain most cases of altered DPD activity and response to 5-FU. Furthermore, variations of DPYD expression in cancer patients have been reported; however, the underlying molecular mechanism is unclear. This suggests that regulation of DPYD expression may be an additional mechanism to control DPD activity. In this study, we focused on epigenetic regulation of DPD and specifically investigated the role of histone methylation on DPYD expression. Inhibition of the H3K27 methyl-transferase Ezh2 by either GSK-126 or a dominant-negative histone H3 mutant significantly increased DPYD expression in various cell lines. The expression of thymidylate synthetase, a major target of 5-fluorouracil toxicity, was not altered. Consistent with elevated DPYD expression, cells that lost H3K27me3 were more resistant to 5-fluorouracil. Furthermore, we demonstrated that Ezh2 and H3K27me3 were enriched on the promoter and the first exon of DPYD in low-DPD expressing cells, but not in cell lines with high DPD levels. Additionally, the enrichment of H3K27me3 on the DPYD promoter was negatively correlated with cellular DPD activity in peripheral mononuclear cells from healthy volunteers. Finally, CRISPR/Cas9-mediated targeting of Ezh2 to the DPYD promoter artificially increased H3K27me3 and suppressed DPYD expression. Collectively, these data suggest that histone methylation can regulate DPYD expression, providing a previously unrecognized mechanism of 5-fluorouracil sensitivity. The tri-methylation of H3K27 is a potential biomarker for guiding individualized 5-FU therapy. Citation Format: Rentian Wu, Steven Offer, Calvin Jerde, Garrett Dunlap, Robert Diasio. Histone H3K27 tri-methylation regulates DPYD expression and cellular sensitivity of 5-fluorouracil. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B49.
Aphasia
Authors: Norman Geschwind
Journal: New England Journal of Medicine (1971)

APHASIA, a common, distressing, and often permanent aftereffect of neurologic disease, has received little attention in recent years not only in general medical publications but even in the neurologic literature. This neglect has resulted from the idea that the aphasias are exotic disorders, of little practical value to the clinician, and not susceptible to experimental analysis, and that discussion of them demands a penchant for abstruse philosophical speculation. Limitations of space preclude dealing with all these misconceptions, and this article will concentrate only on the practical clinical uses of a knowledge of aphasia.Most clinicians have been taught an apparently . . .
Abstract P5-03-05: Genomic analysis and efficacy of entinostat in basal-like and HER2-overexpressing models
Authors: M Tanioka, J Usary, DB Darr, CJ Harrell, CM Perou
Journal: Cancer Research (2016)

Abstract Background. The histone deacetylase inhibitor Entinostat has been under development for patients with metastatic estrogen receptor-positive breast cancer, and its use in Basal-like and HER2-overexpressing breast cancer has been limited. Here we provide results of a study using cell-lines and genetically engineered mouse (GEM) models of breast cancer to examine the effects of Entinostat and combination therapies on multiple in vitro and in vivo models. Methods. Breast cancer cell lines SKBR3, BT474 and MCF-7 were treated with or without Entinostat at their IC50 doses and their gene expression profiles determined. Two breast cancer GEM models (MMTV-neu and C3-Tag) were used to test the efficacy of Entinostat alone, or in combination with cyclophosphamide, or a murine version of an anti-mouse PD1 immune checkpoint inhibitor. Results: Entinostat was an effective in vitro drug with IC50 ranging from 700 to 1500 nM. Supervised analysis of gene expression data coming from treated cell lines showed induction of multiple major histocompatibility complex (MHC) class I/II genes on 6p21. In addition, several MHC genes were also upregulated in C3-Tag treated by Entinostat; because of these findings, the GEM models are currently being treated with the combination of Entinostat and the anti-mouse PD-1 inhibitor. In vivo, GEM tumors treated only with Entinostat were observed to have high objective response rates of 88% and 33% in MMTV-Neu and C3-Tag, respectively. The combination with cyclophosphamide provided significant improvements in the C3-Tag mice over either agent alone, with 11 of 17 mice achieving a CR or PR, and an extension of overall survival (98 days vs 33 days); Entinostat (42d, p=0.002) and Cytoxan (47d, p=0.001). Conclusions. Entinostat showed anti-tumor activity in vitro and in vivo, and was synergistic with cyclophosphamide in the Basal-like C3-Tag mouse model. The upregulation of MHC genes induced by Entinostat at RNA level suggested the interaction with immune response, which is currently under study and will be presented. Citation Format: Tanioka M, Usary J, Darr DB, Harrell CJ, Perou CM. Genomic analysis and efficacy of entinostat in basal-like and HER2-overexpressing models. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-03-05.
Nutrition and Metabolism in Fields Collateral to Tissue Culture&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: André Lwoff
Journal: JNCI Journal of the National Cancer Institute (1957)

Nutrition and Metabolism in Fields Collateral to Tissue Culture Get access André Lwoff André Lwoff Institut Pasteur, Paris, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 4, October 1957, Pages 511–538, https://doi.org/10.1093/jnci/19.4.511 Published: 01 October 1957 Article history Received: 28 May 1957 Published: 01 October 1957
DISLOCATION OF THE SACRO-ILIAC JOINT
Authors: Z B Friedenberg
Journal: JAMA (1921)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Survival of patients with cystic fibrosis.
Authors: U Brook, D Fried
Journal: BMJ (1989)

cardiorespiratory arrest (the cause for which was not established).During her resuscitation she was dragged across a floor and received severe full thickness lacerations to the purpuric and atrophic areas of skin on both arms and both legs.The skin loss on her right leg required grafting.She was discharged seven weeks after admission.Subsequently she had pain and discomfort in areas of scar tissue.She required beclomethasone 1-1 5 mg daily for her asthma.While she was stabilised on a dose of 1 mg beclomethasone daily a short tetracosactrin test showed borderline impairment of her adrenal function (basal plasma cortisol concentration 150 nmol/l, 30 minutes after tetracosactrin 0-25 mg intramuscularly 531 nmoL/l).Although senile purpura and corticosteroid purpura resemble each other closely,4 this patient's age, the location of bruising on her legs4 and the appearance of the bruising some months after taking higher doses of inhaled beclomethasone suggest that her purpura was induced by the steroid.Doctors should continue to be aware of the possibility of appreciable systemic side effects of this form of treatment.
Port Huron
Authors: Janet M. Torpy
Journal: JAMA (2012)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abstract IA10: Extracellular RNA: A next frontier of biomarker research for precision medicine
Authors: Muneesh Tewari
Journal: Clinical Cancer Research (2016)

Abstract Development of effective, minimally invasive biomarker approaches for cancer is critical for enabling precision oncology. Whereas circulating tumor DNA (ctDNA) is one such approach that is now beginning to reach the clinic after an extended period of development, circulating extracellular RNA (exRNA) is a more recent discovery and represents a new frontier for precision medicine biomarker development. I will review the recent history of extracellular circulating RNA, beginning with the discovery of circulating microRNAs and extending to consider other classes of RNA found in human plasma. I will compare and contrast ctDNA and exRNA approaches, and highlight current challenges as well as possibilities for development of circulating exRNAs as biomarkers for precision oncology. Citation Format: Muneesh Tewari. Extracellular RNA: A next frontier of biomarker research for precision medicine. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA10.
Abnormal prolactin response to haloperidol challenge in men with schizophrenia
Authors: N A Keks, D L Copolov, B S Singh
Journal: American Journal of Psychiatry (1987)

Fourteen drug-free male patients with schizophrenia had a smaller and slower prolactin response to 0.5 mg of intravenous haloperidol than 14 normal age- and sex-matched control subjects. This finding supports the presence of dopaminergic dysfunction in schizophrenia.
Cocktail Therapy of 177Lu-PSMA-617 and 177Lu-EDTMP in Patients With mCRPC
Authors: Chandrasekhar Bal, Madhav Prasad Yadav, Sanjana Ballal
Journal: Clinical Nuclear Medicine (2016)

Prostate cancer is the second most common primary tumor affecting men worldwide. Among them, 10–20% develop castration resistant prostate cancer (CRPC). 68Ga-PSMA-PET/CT is an important theranostic agent for the evaluation of CRPC to assess the feasibility of treatment with 177Lu-PSMA-617 which is a novel therapeutic agent. Interestingly, in certain cases, we have observed non–PSMA-avid lesions despite raised sPSA levels. In this regard, we present a case of cocktail therapy applied using 177Lu-PSMA-617 and 177Lu-EDTMP therapy in a 38-year-old male CRPC patient with both soft tissue and extensive skeletal metastases.
Adjuvant therapy of lung cancer.
Authors: J Merk, G Leschber
Journal: BMJ (1977)

To improve outcome of patients with lung cancer, the leading cause of cancer mortality worldwide, a multidisciplinary approach is required. Only approximately 30% of all lung cancer patients present with early stage disease (IA-IIIA). For non-small cell lung cancer (NSCLC) complete surgical resection is currently considered to be the optimal treatment, but high rates of recurrence even after complete resection require to investigate regimes of additional therapy. In the last years, evidence for adjuvant chemotherapy in stage II and III of NSCLC was shown, supported by large clinical trials and meta-analyses, while for stage IB disease the role of adjuvant chemotherapy remains controversial. Further there is actually no evidence to support the routine use of adjuvant radiation or radio-chemotherapy in completely resected patients. For small cell lung cancer (SCLC) a multimodality adjuvant approach is feasible in early stages, his definitive value however should be evaluated in further randomized trials. Current efforts are directed toward identification of prognostic and predictive markers to individualize treatment stratification, a realistic goal for the future. The current status and future perspectives of adjuvant therapy in lung cancer are reviewed in this manuscript.
Differences in neuropsychological and academic achievement between adolescent delinquents and status offenders
Authors: R Famularo, T Fenton, R Kinscherff, R Barnum, S Bolduc, D Bunschaft
Journal: American Journal of Psychiatry (1992)

This study sought to determine whether neurocognitive factors could discriminate delinquents brought before a juvenile court in a large urban area from nondelinquent status offenders brought before the same court.Psychological tests were administered to 216 adolescents, aged 13-15 years, presenting to a large urban juvenile court. One hundred ten delinquents (65 male and 45 female) were compared to 106 high-risk nondelinquents (65 male and 41 female) on the WISC-R subtests, the Wide Range Achievement Test, and the Memory for Designs Test.Discriminant analysis revealed that the male delinquents could not be discriminated from the comparison group of male status offenders on the basis of scores on any of the measures. Among the female subjects, scores on reading, arithmetic, digit span, and picture completion subtests and the Memory for Designs Test differed significantly between groups, with some of the findings favoring status offenders and others favoring delinquents.Overall, the findings did not support the hypothesis that inferior intelligence is an independent risk factor for delinquent behavior.