tbuckley/cabot-search huggingface dataset:
The Natural Processes of Healing in Pulmonary Tuberculosis.
Journal: JAMA (1927)

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 P3-06-11: Understanding resistance mechanisms of PIK3a inhibition in breast cancer
Authors: X Le, F Luo, D Treacy, G Wulf, L Garraway
Journal: Cancer Research (2016)

Abstract Breast cancer is the most common non-cutaneous cancer in women worldwide. PIK3CA is the most frequently mutated oncogene in all invasive breast cancers, with about one third of cases harboring activating mutations. Small molecule therapeutics targeting PI3K pathway has been developed and investigated for a decade. Everolimus (an mTOR inhibitor) is now successfully used in conjunction with hormonal therapy in patients with metastatic hormone-receptor positive breast cancers. Inhibitors of PI3Kα have shown promise as a single agent as well as in combination with hormonal therapies. The high rate of primary and acquired resistance; however, limits clinical usage of this class of drugs. There is an urgent need to understand the resistance mechanisms of PI3K inhibition and develop strategies to overcome the resistance in breast cancer. We took a genome-scale functional screening approach to identify resistance mechanisms to PI3K inhibition in breast cancer. We performed a whole-genome lentiviral open-reading frame (ORF) overexpression screen in a breast cancer cell line (T47D) in the presence of a PI3Kα inhibitor. We screened a total of 15,590 ORFs and identified 75 genes whose overexpression confers resistance to PI3K inhibition. Once we validate the hits, we plan to determine the mechanisms by which the genes confer resistance. We also plan to perform RNA-sequencing in patient samples with PI3Ka resistance to evaluate the clinical relevance of these genes and pathways. Citation Format: Le X, Luo F, Treacy D, Wulf G, Garraway L. Understanding resistance mechanisms of PIK3a inhibition in breast cancer. [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 P3-06-11.
Abstract B31: Establishment of a 5-fluorouracil-resistant esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase gene amplification
Authors: Osamu Kikuchi, Kiichiro Baba, Shinya Ohashi, Manabu Muto
Journal: Cancer Research (2016)

Abstract 5-Fluorouracil (5-FU) is the key drug for the treatment of esophageal squamous cell carcinoma (ESCC), however, resistance to 5-FU remains a critical limitation to the clinical use. To clarify the mechanisms of 5-FU resistance in ESCC, we have established a 5-FU-resistant ESCC cell line TE-5R from parental TE-5 cells, by treatment with the step-wise continuous increasing concentrations of 5-FU. The half maximal inhibitory concentration of 5-FU showed that TE-5R cells were 15.6-fold resistant to 5-FU in comparison with TE-5 cells. Intracellular 5-FU concentration was significantly lower in TE-5R cells than in TE-5 cells. TE-5R cells showed regional copy number amplification of chromosome 1p including the DPYD gene, as well as high mRNA and protein expressions of dihydropyrimidine dehydrogenase (DPD), an enzyme involved in 5-FU degradation, whereas copy number of the other 5-FU metabolism-related genes in TE-5R cells did not changed from TE-5 cells. Gimeracil, a DPD inhibitor, sharply restored 5-FU resistance and increased intracellular 5-FU concentration in TE-5R cells. Next, to investigate whether other 5-FU metabolism-related genes contributed to 5-FU resistance in TE-5R cells, we added microarray gene expression assay and no significant differences in the expression of 5-FU metabolism-related genes were detected. These results indicate that 5-FU resistance in TE-5R cells is based on a DPD-dependent rapid degradation of 5-FU. Taken together, we established novel 5-FU-resistant TE-5R cells, which may have obtained 5-FU resistance with DPD copy number amplification and consequent overexpression, providing a critical insight to explore a new strategy against 5-FU-resistant ESCC using DPD inhibitor. Citation Format: Osamu Kikuchi, Kiichiro Baba, Shinya Ohashi, Manabu Muto. Establishment of a 5-fluorouracil-resistant esophageal squamous cell carcinoma cells with dihydropyrimidine dehydrogenase gene amplification. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B31.
Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups
Authors: MV Ragni, DA Amato, ML LoFaro, V DeGruttola, C Van Der Horst, ME Eyster, CM Kessler, GF Gjerset, M Ho, DM Parenti
Journal: Blood (1995)
Calcium Ionophores at Concentrations Mitogenic to Normal Murine T Cells Inhibit the Proliferation of Tumor Cells In Vitro
Authors: M Nagarkatti, P S Nagarkatti
Journal: Cancer Communications (1989)

The Ca2+ ionophores, A23187 and ionomycin, when used alone at 0.3-5 microM concentrations, were mitogenic to normal resting murine T cells. At these doses, the Ca2+ ionophores inhibited DNA synthesis and growth of a T cell lymphoma and several murine transformed cell lines. Treatment of tumor cells with either ionophore caused a rapid increase in intracellular Ca2+ [( Ca2+]i) followed by a decline and, thereafter, maintenance of a steady level that was slightly above the preactivation levels of [Ca2+]i. Cell cycle analysis revealed that each of the Ca2+ ionophores inhibited tumor cell transition from the G1 phase to the S phase of the cell cycle and, possibly, arrested cells already in the S-phase. These data suggest that an early activation signal such as increased [Ca2+]i may initiate surface to nuclear signals that are different in normal T cells than in transformed cells that may receive opposite effects. Our studies suggest that non-specific activation of tumor cells by various stimuli may provide a useful approach to treat tumors in vivo.
Adjuvant therapy for breast cancer: understanding the overview. International Breast Cancer Study Group.
Authors: R D Gelber, A Goldhirsch, A S Coates
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.3.580 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8445434 Adjuvant therapy for breast cancer: understanding the overview. International Breast Cancer Study Group. R D GelberxR D GelberSearch for articles by this author , A GoldhirschxA GoldhirschSearch for articles by this author , A S CoatesxA S CoatesSearch for articles by this author Show More Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115. https://doi.org/10.1200/JCO.1993.11.3.580 First Page PDF © 1993 by American Society of Clinical Oncology
Abstract 4099: IGF1R signaling connects DNp73-mediated EMT with the acquisition of cancer stem cell properties
Authors: Claudia Meier, Marc Steder, Philip Hardtstock, Vijay Alla, Brigitte M. Pützer
Journal: Cancer Research (2015)

Abstract Metastatic spread is the major cause of cancer-associated mortality and induced in primary tumor cells by the acquisition of mesenchymal features. Emerging evidence suggests that metastasis-initiating cancer cells undergoing epithelial-mesenchymal transition (EMT) possess stem cell-like traits. In this study, we demonstrate that oncogenic DNp73, an inhibitor of p53 tumor suppressor family members, has a fundamental role in driving both, transition into a mesenchymal state and providing cancer cells with stem cell-like properties through constitutive activation of IGF1R signaling. In patient melanoma tissues, DNp73 expression correlates with increased Breslow depth and is enriched in skin cancer metastases. Knockdown of endogenous DNp73 in highly metastatic cell lines abolishes the aggressive phenotype, whereas tumor xenografts overexpressing DNp73 possess significantly greater capacity to invade the surrounding tissue and form metastatic lesions. Transition from an epithelial to a motile mesenchymal phenotype is accompanied by a drastic reorganization of the cytoskeleton and modulation of cell-cell adhesion molecules. Importantly, regulation of EMT by DNp73 is induced through activation of IGF1R-AKT signaling followed by an increase of Slug and loss of E-cadherin. Additionally, we identified a novel interplay between DNp73 and IGF1R in the development of cancer stemness. Tumor spheres derived from metastatic melanoma cells with endogenously high DNp73 display a strong capacity for self-renewal and tumor growth after subcutaneous injection in mice compared to DNp73-depleted cancer stem cells. Our results clearly demonstrate that DNp73-driven stemness involves IGF1R activation. Selective inhibition of IGF1R blocks DNp73-mediated upregulation of Nanog, Oct4 and CD133, which is accompanied by a decrease in spheroid formation and tumor invasiveness. Taken together, our findings show for the first time that DNp73 is crucial to endow cancer cells with mesenchymal properties and the ability to self-renew, which is responsible for malignant progression and tumor dissemination. Moreover, we establish IGF1R as driving force for a DNp73-induced aggressive cancer phenotype, highlighting the DNp73-IGF1R cascade as promising therapeutic target to selectively prevent metastasis initiation. Citation Format: Claudia Meier, Marc Steder, Philip Hardtstock, Vijay Alla, Brigitte M. Pützer. IGF1R signaling connects DNp73-mediated EMT with the acquisition of cancer stem cell properties. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4099. doi:10.1158/1538-7445.AM2015-4099
Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non–Small Cell Lung Cancer, and Other Solid Tumors
Authors: Amita Patnaik, Lee S. Rosen, Sara M. Tolaney, Anthony W. Tolcher, Jonathan W. Goldman, Leena Gandhi, Kyriakos P. Papadopoulos, Muralidhar Beeram, Drew W. Rasco, John F. Hilton, Aejaz Nasir, Richard P. Beckmann, Andrew E. Schade, Angie D. Fulford, Tuan S. Nguyen, Ricardo Martinez, Palaniappan Kulanthaivel, Lily Q. Li, Martin Frenzel, Damien M. Cronier, Edward M. Chan, Keith T. Flaherty, Patrick Y. Wen, Geoffrey I. Shapiro
Journal: Cancer Discovery (2016)

We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Dose-limiting toxicity was grade 3 fatigue. The maximum tolerated dose was 200 mg every 12 hours. The most common possibly related treatment-emergent adverse events involved fatigue and the gastrointestinal, renal, or hematopoietic systems. Plasma concentrations increased with dose, and pharmacodynamic effects were observed in proliferating keratinocytes and tumors. Radiographic responses were achieved in previously treated patients with breast cancer, NSCLC, and melanoma. For hormone receptor-positive breast cancer, the overall response rate was 31%; moreover, 61% of patients achieved either response or stable disease lasting ≥6 months.Abemaciclib represents the first selective inhibitor of CDK4 and CDK6 with a safety profile allowing continuous dosing to achieve sustained target inhibition. This first-in-human experience demonstrates single-agent activity for patients with advanced breast cancer, NSCLC, and other solid tumors. Cancer Discov; 6(7); 740-53. ©2016 AACR.See related commentary by Lim et al., p. 697This article is highlighted in the In This Issue feature, p. 681.
Abstract B16: Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated ovarian cancers.
Authors: Benjamin Bitler, Ie-Ming Shih, Rugang Zhang
Journal: Clinical Cancer Research (2016)

Abstract ARID1A, a chromatin remodeler, shows one of the highest mutation rates across many cancer types. Notably, ARID1A is mutated in ~50% of ovarian clear cell carcinomas and ~30% of ovarian endometrioid carcinomas. To date, clinically applicable targeted cancer therapy based on ARID1A mutational status has not been described. Here we show that inhibition of the EZH2 methyltransferase acts in a synthetic lethal manner in ARID1A mutated ovarian cancer cells. ARID1A mutational status correlates with response to the EZH2 inhibitor. We identified PIK3IP1 as a direct ARID1A/EZH2 target, which is upregulated by EZH2 inhibition and contributes to the observed synthetic lethality by inhibiting PI3K/AKT signaling. Significantly, EZH2 inhibition causes regression of ARID1A mutated, but not wild-type, ovarian tumors in vivo. Together, these data demonstrate for the first time a synthetic lethality between ARID1A mutation and EZH2 inhibition. They indicate that pharmacological inhibition of EZH2 represents an urgently needed, novel treatment strategy for ARID1A mutated ovarian cancers. Citation Format: Benjamin Bitler, Ie-Ming Shih, Rugang Zhang. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated ovarian cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B16.
The vaccination campaign against 2009 pandemic influenza A(H1N1) and its continued importance in view of the uncertainty surrounding the risk associated with the pandemic
Authors: S Tsiodras, V Sypsa, A Hatzakis
Journal: Eurosurveillance (2010)

Preview this article: The vaccination campaign against 2009 pandemic influenza A(H1N1) and its continued importance in view of the uncertainty surrounding the risk associated with the pandemic, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/15/3/art19468-en-1.gif
Comparison of dual-probe CISH with FISH in the determination of HER2/chromosome 17 for patients with breast cancer in China.
Authors: G. Ren, Y. Bai, M. Han, B. Wang
Journal: Journal of Clinical Oncology (2010)

1149 Background: The aim of this investigation was to evaluate the clinical application of dual-probe chromogenic in situ hybridization (CISH) in the testing of HER2 gene status in patients with breast cancer by comparison with fluorescence in situ hybridization (FISH). The potential impact of chromosome 17 polysomy in the determination of HER2 status was also evaluated. Methods: We collected 146 paraffin-embedded tissue sections of breast cancer and determined HER2 gene and chromosome 17 copy numbers using CE approved commercial kits of dual-probe FISH (for 146 cases) and dual-probe CISH (for 73 cases), respectively. The results were interpreted based on either HER2 gene copy number or the ratio of HER2/chromosome 17 (ASCO/CAP, 2007). Results: Of the 73 cases measured by both FISH and CISH methods, the concordance between two methods for negative and positive results was 91.7% and 97.4%, respectively, while the overall concordance between the two methods was 95.9%. Of the 146 cases measured by FISH, 13 cases were interpreted as equivocal if only HER2 copies were counted, which was 1.6-fold (13/8) higher than the equivocal cases interpreted by counting the ratio of HER2/chromosome 17. Moreover, 3 of 63 (4.8%) HER2 positive cases determined by HER2 copies turned out to be HER2 negative determined by the ratio of HER2/chromosome 17, In CISH results, 1 of 33 (3.0%) positive cases was turned to negative by the comparison of two corresponding scoring methods. We also observed from FISH results that there were more chromosome 17 polysomy cases (63.5%, 40/63) in HER2 positive subgroup than those (37.3%, 28/75) in HER2 negative subgroup. (p=0.002). In addition, CISH method, which simultaneously shows HER2 signals and morphology, has obvious advantages in HER2 determination of one case with DCIS. Conclusions: Our HER2 results determined by dual-probe CISH method were almost perfect agreed with the corresponding results determined by FISH method, indicating dual-probe CISH is a reliable alternative to FISH in HER2 testing. This study also indicates that the diagnostic accuracy may be increased when HER2 and chromosome 17 are simultaneously tested and counted. No significant financial relationships to disclose.
Case 51-1966
Authors: Gerald S. Foster, Wallace A. Jones
Journal: New England Journal of Medicine (1966)

Presentation of Case First admission. A fifty-two-year-old woman entered the hospital because of pain in the chest.She had felt well until two months previously, when there was the onset of episodes of bandlike tightness in the precordial region, with radiation of pain to the upper portions of the arms. The attacks were accompanied by belching, occurred with increasing frequency and persisted for several hours. Three weeks before admission the stools were black for several days, but there was no passage of fresh blood or hematemesis. During the three days before entry she vomited on several occasions.At the . . .
Abstract A22: Functional long noncoding RNAs in castration-resistant prostate cancer
Authors: Teng Fei, Yiwen Chen, Xiaole Shirley Liu, Myles Brown
Journal: Cancer Research (2016)

Abstract Prostate cancer progression from an androgen-dependent state to an androgen-independent phase, which is also referred to castration-resistant prostate cancer (CRPC), not only results in cancer refractory to androgen deprivation therapy but also marks lethal prognosis. Androgen receptor (AR) plays central roles in both normal prostate development and prostate cancer progression. Aberrant androgen/AR signaling activity is often associated with the development of CRPC, such as increased synthesis of steroid hormone, increased expression of AR, emergence of specific AR variants etc. However, deeper understanding of detailed mechanism of CRPC development is still necessary in order to discover novel effective drug targets for the treatment of CRPC. Recent studies suggest that long non-coding RNA (lncRNA) can be extensively functional rather than just transcriptional noise and lncRNAs are also widely involved in the pathogenesis of different types of cancers including prostate cancer. To further investigate the potential role of lncRNAs during prostate cancer progression, we profiled lncRNA transcriptome using RNA-seq in prostate cancer cells in the presence or absence of androgen treatment. In combination with AR cistrome data, we identified a set of lncRNAs that are directly regulated by androgen/AR signaling. A specific lncRNA was identified as androgen/AR repressed target gene in androgen-dependent cells while showing significant higher expression in androgen-independent cells that mimics CRPC state. Interestingly, knockdown of this lncRNA specifically attenuates the growth of androgen-independent cells while has little effect on androgen-dependent cells. To understand the detailed mechanism, we identified the downstream target genes using RNA-seq upon silencing this lncRNA in either androgen-dependent or -independent cells. Moreover, this lncRNA is located in a region that is frequently amplified in CRPC and highly expressed in a subset of CRPC patients. We suggest that this lncRNA, along with other androgen/AR targets, may play a role during the development of CRPC and could serve as a potential drug target for the treatment of CRPC. Note: This abstract was not presented at the conference. Citation Format: Teng Fei, Yiwen Chen, Xiaole Shirley Liu, Myles Brown. Functional long noncoding RNAs in castration-resistant prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A22.
Abstract P1-10-12: Biopsychosocial concerns of adolescent young adults (AYA) with breast cancer
Authors: R Smith, J Mortimer, M Loscalzo, K Clark
Journal: Cancer Research (2016)

Abstract Background: The natural history of breast cancer in the AYAs with breast cancer is reported to be more aggressing than that observed in older women. We wanted to determine the level of biopsychological distress in this population compared with women in other age groups. Methods: All new patients seen at City of Hope complete a tablet-based self report biopsychosocial screening questionnaire (SupportScreen®). Patients are asked to score a series of problems on a 5-point Likert scale ("not a problem" to "very severe problem") and are asked if they are interested in obtaining help for that problem. Results: To date 1,159 women have undergone screening; 79 pts (6.9%) were age 18-39 yrs (AYA), 807 (69.6%) age 40-64 yrs, and 273 (23.6%) &amp;gt; 65 yrs. The concerns that were unique to the AYA population included: Ability to have children (p=0.001) and physical appearance (p=0.047 for 40-64 yrs and p=0.018 for age &amp;gt; 65 yrs). Older women were more concerned that AYAs or middle aged women about transportation (p=0.008), walking, climbing stairs (p=0.000). Compared to older women, those age 40-64 yrs were more likely to identify feeling anxious or fearful (p=0.032) and managing work, school or home life (p=0.018). In comparison to AYAs, those age 40-64 yrs had more distress related to recent weight change (p=0.034) and difficulty sleeping (p=0.006). Conclusions: Biopsychosocial concerns change over the continuum of age. Compared to other age groups, the AYA population was more concerned about their ability to have children and their physical appearance. In other domains of distress, they were comparable to women age 40-65 yrs. Citation Format: Smith R, Mortimer J, Loscalzo M, Clark K. Biopsychosocial concerns of adolescent young adults (AYA) with breast cancer. [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 P1-10-12.