tbuckley/cabot-search huggingface dataset:
Has Marijuana Legalization Increased Marijuana Use Among US Youth?
Authors: Wayne Hall, Megan Weier
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
The search continues: Looking for predictive biomarkers for response mTOR inhibition in endometrial cancer.
Authors: L. A. Meyer, B. M. Slomovitz, B. Djordjevic, J. M. Galbincea, T. A. Johnston, M. Munsell, J. K. Burzawa, M. Huang, R. Broaddus, D. A. Iglesias, R. L. Coleman, D. M. Gershenson, T. W. Burke, J. Wolf, K. H. Lu
Journal: Journal of Clinical Oncology (2011)

5016 Background: Everolimus is an oral rapamycin analog that selectively inhibits mTOR. PTEN mutations occur in 40-60% of endometrial cancer (EC). Although PTEN loss leads to constitutive activation of AKT and up-regulation of mTOR, it is not clear which EC patients will benefit from this targeted therapy. PS6K is a downstream marker of mTOR activation. Prior studies suggest KRAS mutations are associated with resistance to everolimus. We evaluated primary tumor specimens to determine if expression of biomarkers in the mTOR pathway or KRAS mutations would predict response to therapy. Methods: Correlative studies evaluating PTEN and PS6K expression by immunohistochemistry (IHC) and KRAS mutational analysis were performed from tissue blocks of primary tumor. Response to therapy was estimated with Fisher’s exact test. Positive predictive value (PPV) for each variable was calculated. Tumor from patients enrolled in a single institution, open-labeled, single arm, Phase II study in pretreated patients with recurrent EC of endometrioid histology was utilized. Patients received everolimus (10 mg PO daily/28 day cycles) until progression or toxicity. Results: 6 of 28 (21%) evaluable patients had CBR, with prolonged stable disease at 20 weeks. 24/28 specimens were evaluated for PTEN. Loss of PTEN expression by IHC did not predict response to Everolimus (p=0.62) and had a PPV of 0.13. 5/6 (83%) of patients with SD maintained PTEN expression. 28/28 specimens were evaluable for PS6K expression. PS6K expression by IHC also did not predict response (p=0.65) with a PPV 0.14. 23/28 specimens were evaluable for KRAS mutations. KRAS mutations did not predict response (p=1) with a PPV of 0.14. Interestingly, 80% (4/5) of those with SD were KRAS wildtype. Conclusions: Loss of PTEN expression, PS6K expression and KRAS mutational status did not significantly correlate with response to therapy. However, the trend seen in other studies of KRAS as a marker of resistance to mTOR inhibitors such as everolimus was supported by our findings and deserves further study. In addition, discovery of new predictive biomarkers is needed to identify subsets of patients who will benefit from therapies targeting the mTOR pathway.
Intra-articular Corticosteroids and Knee Osteoarthritis
Authors: David T. Felson
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 575: Identification of response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors
Authors: Jonathan Strosberg, Mauro Cives, Marjorie Brelsford, Michael Black, Alan Meeker, Masoumeh Ghayouri
Journal: Cancer Research (2015)

Capecitabine and temozolomide are active in the treatment of metastatic pNETs, with response rates ranging from 30% to 70%. Several small retrospective series have suggested that MGMT deficiency may predict response to temozolomide, however expression of MGMT has not been validated as a predictive biomarker. Cytotoxic chemotherapy is thought to be most active in aggressive tumors, however the ki-67 index has not been formally evaluated as a predictive factor. It is unclear whether chromosomal instability (which correlates with alternate lengthening of telomeres) predicts response. 144 patients with pNET who underwent treatment with cape/tem were retrospectively evaluated for radiographic response. The predictive role of ki-67% and MGMT by IHC as well as ALT activation by FISH was assessed on up to 59 evaluable archival specimens. Frequently altered genes in pNETs were also sequenced and their status was correlated to the radiographic response. The ORR was 63%. Response to treatment was significantly higher in tumors with ki-67>5% (n = 28) as compared to tumors with ki-67≤5% (n = 31) (ORR: 64% vs 29%; p = 0.006). MGMT status (p = 0.358) and ALT pathway activation (p = 0.174) were not predictive of response. pNETs with ki-67 >5% are more likely to respond to cape/tem. MGMT status appears to have no correlation with response.Citation Format: Jonathan Strosberg, Mauro Cives, Marjorie Brelsford, Michael Black, Alan Meeker, Masoumeh Ghayouri. Identification of response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. [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 575. doi:10.1158/1538-7445.AM2015-575
Synthetic Retinoid Am80 Ameliorates Chronic Graft-Versus-Host Disease.
Authors: Hisakazu Nishimori, Haruko Sugiyama, Koichiro Kobayashi, Yoshiko Yamasuji, Eisei Kondo, Katsuji Shinagawa, Mitsune Tanimoto, Kengo Takeuchi, Yoshinobu Maeda
Journal: Blood (2009)
Intra-articular Corticosteroids for Osteoarthritis of the Knee
Authors: Bruno R. da Costa, Roman Hari, Peter Jüni
Journal: JAMA (2016)

<h3>Clinical Question</h3> Are intra-articular corticosteroids associated with improvement in pain and physical function compared with sham injection or no intervention in patients with knee osteoarthritis? <h3>Bottom Line</h3> Intra-articular corticosteroids may be associated with moderate improvement in pain and a small improvement in physical function up to 6 weeks after injection. However, the quality of the evidence is low.
Abstract 996: Retinoic acids activate autophagy in breast cancer cells through the FOXO3A-RARA pathway and blocking autophagy enhances retinoic acid-mediated cell death
Authors: Anna M. Schlaefli, Enrico Garattini, Mario P. Tschan
Journal: Cancer Research (2015)

Abstract A series of pre-clinical studies showed promising anti-cancer effects of retinoic acids (RA) in breast cancer models. However, clinical studies were mostly disappointing possibly also due to the trial design and emerging resistances. One way to confer resistance to a given treatment is activation of protective autophagy. Autophagy is a cellular recycling mechanism that is characterized by the formation of double-membraned autophagosomes. Autophagosomes engulf bulk cytoplasm or selected contents thereof and transfer them to lysosomes for degradation. Activation of autophagy upon anti-cancer treatment may allow prolonged survival of the tumor cells. We therefore asked if autophagy is activated by all-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, in mammary tumor cells and if autophagy might protect the cells from the pro-apoptotic effects of ATRA. We found that ATRA induces autophagic flux in ATRA-sensitive SKBR3 but not in -resistant MD-MBA- 453 human breast cancer cells as seen by increased LC3B-II protein abundance and turnover of long-lived proteins. Moreover, using RA receptor alpha (RARA), RARB and RARG agonists as well as RARA knockdown breast cancer cells we demonstrated that activation of autophagy by RA depends on RARA expression. RA-treatment also caused induction of the transcription factor FOXO3A, a known transcriptional target of RARA. Since the expression of several autophagy genes namely the ATG8 family members, Beclin-1 and PI3KC3 are controlled by FOXO3A, we tested if FOXO3A might link ATRA-mediated signaling to autophagy activation. Indeed, depleting FOXO3A in SKBR3 cells resulted in significantly decreased autophagic activity and autophagy gene expression upon RA treatment. Importantly, blocking autophagy by knocking down the key autophagy genes ATG5 or ATG7 in breast cancer cells resulted in significantly increased apoptosis under ATRA treatment. Of note, inhibition of autophagy also attenuated cyto-differentiation similarly to the phenotype seen in RARA knockdown breast cancer cells. In summary, our data demonstrate for the first time that retinoic acids induce autophagy in breast cancer cells via the FOXO3A-RARA axis. Furthermore, inhibition of autophagy results in enhanced ATRA-mediated apoptosis representing a potential new treatment strategy for a selected group of breast cancer patients. Citation Format: Anna M. Schlaefli, Enrico Garattini, Mario P. Tschan. Retinoic acids activate autophagy in breast cancer cells through the FOXO3A-RARA pathway and blocking autophagy enhances retinoic acid-mediated cell death. [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 996. doi:10.1158/1538-7445.AM2015-996
A Phase I Trial of Autologous Dendritic Cell Therapy for Chronic Myelogenous Leukemia.
Authors: Mark Robert Litzow, Allan B. Dietz, Peggy A. Bulur, Greg W. Butler, Stephanie R. Fink, Louis Letendre, Sarah F. Paternoster, Ayalew Tefferi, Antje Hoering, Stanimir Vuk-Pavlovic
Journal: Blood (2004)
Dexamethasone (D), High Dose Ara-C (HA) and Carboplatin (DHAC) with or without Rituximab (R) Is an Effective Salvage Regimen for Patients with Relapsed/Refractory B-Cell Lymphoma in Preparation for Autologous Stem Cell Transplantation.
Authors: Raymond Cruz, Myron S. Czuczman, Francisco Hernandez, Ajay Kanra, Swaminathan Padmanabhan
Journal: Blood (2006)
Abstract 4803: BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma
Authors: Olivier Harismendy, Hakan Alakus, Shawn Yost, Brian Woo, Randall French, Grace Y. Lin, Kristen Jepsen, Kelly A. Frazer, Andrew M. Lowy
Journal: Cancer Research (2015)

Abstract Malignant mesothelioma (MM) arises from mesothelial cells that line the pleural, peritoneal and pericardial surfaces. The majority of MMs are pleural and have been associated with asbestos exposure. Previously, pleural MMs have been genetically characterized by the loss of BAP1 (40-60%) as well as loss of NF2 (75%) and CDKN2A (60%). The rare peritoneal form of MM occurs in ∼10% cases. With only ∼300 cases diagnosed in the US per year, its link to asbestos exposure is not clear and its mutational landscape unknown. We analyzed the somatic mutational landscape of 12 peritoneal MM of epitheloid subtype using copy number analysis (N = 9), whole exome sequencing (N = 7) and targeted sequencing (N = 12). Peritoneal MM display few copy number alterations, with most samples having less than 10 Mbp total changes, mostly through deletions and no high copy number amplification. Chromosome band 3p21 encoding BAP1 is the most recurrently deleted region (5/9), while, in contrast to pleural MM, NF2 and CDKN2A are not affected. We further identified 87 non-silent mutations across 7 sequenced tumors, with a median of 8 mutated genes per tumor, resulting in a very low mutation rate (median 1.3 10-6). BAP1 was the only recurrently mutated gene (N = 3/7). In one additional case, loss of the entire chromosome 3 leaves a non-functional copy of BAP1 carrying a rare nonsense germline variant, thus suggesting a potential genetic predisposition in this patient. Finally, with targeted sequencing of BAP1 in 3 additional cases, we conclude that BAP1 is frequently altered through copy number losses (N = 3/12), mutations (N = 3/12) or both (N = 2/12) sometimes at a sub-clonal level. Our findings suggest a major role for BAP1 in peritoneal MM susceptibility and oncogenesis and indicate important molecular differences to pleural MM as well as potential strategies for therapy and prevention. Citation Format: Olivier Harismendy, Hakan Alakus, Shawn Yost, Brian Woo, Randall French, Grace Y. Lin, Kristen Jepsen, Kelly A. Frazer, Andrew M. Lowy. BAP1 mutation is a frequent somatic event in peritoneal malignant mesothelioma. [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 4803. doi:10.1158/1538-7445.AM2015-4803
Long-Term Outcomes of Patients with Systemic Light Chain Amyloidosis (AL) Treated At Diagnosis with Risk-Adapted Stem Cell Transplant and Consolidation with Novel Agents.
Authors: Raymond L. Comenzo, Daniel E Fein, Hani Hassoun, Christina Bello, Joanne F Chou, Sean Devlin, Sergio A Giralt, Heather Landau
Journal: Blood (2012)
Cystoid Macular Edema after Descemet's Stripping Automated Endothelial Keratoplasty
Authors: Koji Kitazawa, Kanae Kayukawa, Koichi Wakimasu, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Kazuhiko Mori, Chie Sotozono, Shigeru Kinoshita
Journal: Ophthalmology (2016)
Abstract IA22: An oncogenic enhancer drives NOTCH1-induced leukemia.
Authors: Adolfo Ferrando
Journal: Clinical Cancer Research (2015)

Abstract Most genetic abnormalities found in cancer are located in intergenic regions and their role in cancer development remains poorly understood. Here we report the identification of a long range enhancer driving NOTCH1-induced transformation in T-ALL. Using genome wide ChIPseq mapping of NOTCH1 binding and functional epigenetic marks in T-ALL we identified a NOTCH1-occupied enhancer located in a gene desert island in 8q24, +1,427 kb 3' from the MYC locus. This regulatory element named N-Me for NOTCH-bound MYC enhancer activates MYC reporter constructs in T-ALL cells and directly interacts with MYC promoter sequences via long range chromatin loops. Notably, high resolution aCGH analysis revealed recurrent focal duplications at chromosome 8q24 encompassing this enhancer in 8/160 (5%) T-ALL cases. Functional characterization of N-Me in T-cell development and transformation using N-Me knockout and conditional knockout mice revealed a major role for this enhancer during thymocyte development and in T-ALL. Thus N-Me null animals showed a marked and selective reduction in thymus size and cellularity and were completely resistant to NOTCH1-induced transformation. Moreover, secondary deletion of N-Me in established NOTCH1 induced leukemias from tamoxifen-inducible N-Me conditional knockout mice induced profound antileukemic effects with extended survival and almost complete suppression of leukemia initiating cell activity. Altogether, these results identify N-Me as a major downstream effector NOTCH1 critically required for MYC expression in T-cell development and leukemia. Citation Format: Adolfo Ferrando. An oncogenic enhancer drives NOTCH1-induced leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA22.
Abstract 1329: Identification of neoantigens recognized by autoantibodies in chemotherapy-treated pancreatic cancer patients
Authors: Giorgia Mandili, Emanuela Mazza, Michela Capello, Daniele Giordano, Paola Cappello, Francesco Novelli
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult cancer to treat, both for lack of effective screening method and for resistance phenomenon. At present surgical resection is the only potentially curative option, but the absence of early symptoms or clinical-pathological markers results in diagnosis at a late, inoperable stage in mostly of cases. Once diagnosed, a number of chemotherapy, radiation and combination therapy regimens are usually used to treat patients, but responses remain poor. However, chemotherapy is able to enhance tumor immunogenicity. Thus more immunogenic neo-antigens can be induced by chemotherapy and targeted by passive or active immunotherapy. We have previously identified a number of Tumor Associated Antigens (TAA) that are recognized by autoantibodies in PDAC patients. One of these, alpha-enolase, was found to have good antigen capability and immunization with DNA coding for alpha-enolase effectively enhanced the survival of genetically engineered mice that develop spontaneously PDAC. To discover neo-antigens that might be selected for immunotherapy, we have analysed antibody response in PDAC patients’ sera before and after chemotherapy. The reactivity of PDAC patients’ sera obtained before and after two rounds of chemotherapy was analysed on 2-dimensional gel electrophoresis proteome map of CF-PAC pancreatic cancer cell line and the antigens recognized by autoantibodies were identified by mass spectrometry. A number of antigens, mainly metabolic enzymes, proteins involved in transcription and structural proteins, were recognized by autoantibody only after one or two rounds of chemotherapy. The identification of common and individual antigens from chemotherapy treated-patients formed the platform for ongoing immunological studies aimed to assess the ability of these neo-antigens, compared to that identified before chemotherapy treatment, to induce specific helper and cytotoxic response to PDAC. A stronger and sustained immune response correlated to survival is expected to be induced by neo-antigens. Validation of these neo-antigens will allow to develop specific immunotherapy combined with chemotherapy. Citation Format: Giorgia Mandili, Emanuela Mazza, Michela Capello, Daniele Giordano, Paola Cappello, Francesco Novelli. Identification of neoantigens recognized by autoantibodies in chemotherapy-treated pancreatic cancer patients. [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 1329. doi:10.1158/1538-7445.AM2015-1329
Reflections on a Prenatal Diagnosis of Trisomy 21 Syndrome
Authors: Amanda Davis
Journal: JAMA Pediatrics (2017)

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
Activity of the Multi-Targeted Kinase Inhibitor, AT9283 on Imatinib-Resistant CML Models.
Authors: Ruriko Tanaka, Matthew S Squires, Shinya Kimura, Asumi Yokota, Kirsty Mallett, Tomoko Smyth, Neil T Thompson, Rina Nagao, Takahiro Yamauchi, Takashi Ushiki, John F Lyons, Taira Maekawa
Journal: Blood (2008)
Impact of Cytogenetics and Prior Therapy on Outcome of AML and MDS after Allogeneic Transplantation.
Authors: Philippe Armand, Haesook T. Kim, Daniel J. DeAngelo, Vincent T. Ho, Corey S. Cutler, Richard M. Stone, Jerome Ritz, Edwin P. Alyea, Joseph H. Antin, Robert J. Soiffer
Journal: Blood (2006)