tbuckley/cabot-search huggingface dataset:
Abstract 07: Using copy number alterations to identify targeted therapies in a preclinical model of osteosarcoma
Authors: Marcus R. Breese, Leanne C. Sayles, Alejandro Sweet-Cordero
Journal: Clinical Cancer Research (2016)

Abstract Osteosarcoma (OS) is an aggressive bone malignancy affecting approximately 400 pediatric patients in the United States annually. Compared with other pediatric cancers, OS has a low 5-year overall survival rate. There are few treatment options for patients that progress on standard therapy, making it important to identify new therapeutic targets for these high-risk patients. At the genomic level, OS is characterized by significant genomic instability, resulting in numerous copy number alterations (CNA) and structural variations (SV). Unfortunately, many of the CNAs and SV events are non-recurrent, making each disease highly patient-specific. We hypothesized that CNAs may be drivers of OS and that we could use patient-specific CNA profiles to identify actionable targets in OS. In order to test this in a preclinical setting, we have developed a robust program for generating and maintaining patient-derived xenografts (PDX) from patients with OS. In a pilot study of 3 patients, we used a combination of tumor/normal whole-genome sequencing (WGS) and commercial gene panel testing to identify potentially druggable targets using CNA. For samples tested with WGS, gene-level CNA was assessed for a number of clinically actionable genes. For each gene, CNA was determined using the normalized ratio of sequencing reads mapped to the gene in the tumor versus the normal sample. The degree of CNA was used to help prioritize potential targets. For the commercially tested samples, genes were either reported as amplified or not. Using these results to inform target selection, we treated each PDX with a drug matched to its corresponding CNA predicted target. In each sample, we saw a significant reduction in the growth rate of the PDX compared to vehicle or a non-matched drug. This suggests that using the patient-specific CNAs to identify drug targets may be an effective strategy in the treatment of OS. Citation Format: Marcus R. Breese, Leanne C. Sayles, Alejandro Sweet-Cordero. Using copy number alterations to identify targeted therapies in a preclinical model of osteosarcoma. [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 07.
Implications of the efficacy of thiothixene and a chlorpromazine- imipramine combination for depression in schizophrenia
Authors: R E Becker
Journal: American Journal of Psychiatry (1983)

The ineffectiveness of antidepressants, and the effectiveness of neuroleptics alone, in the treatment of depressed schizophrenic patients is evidence that a pharmacologically definable depression cannot be demonstrated in schizophrenia. The author reports findings from a double-blind 1-month study of 52 anergic and depressed schizophrenic patients given thiothixene-placebo or chlorpromazine-imipramine. These findings support DSM-III, which does not diagnose intercurrent, secondary depression in the presence of schizophrenia. Consistent with most of the clinical literature, this study also supports the use of a single neuroleptic rather than neuroleptic-antidepressant combinations to treat depressive symptoms secondary to schizophrenia.
CD44 standard isoform expression is associated with diffuse large B cell lymphoma of non-germinal center B cell-like types
Authors: W. Kim, Y. Oh, C. Park
Journal: Journal of Clinical Oncology (2007)

18531 Background: Diffuse large B cell lymphoma (DLBCL) can be subdivided into germinal center B cell-like (GCB) and non- germinal center B cell-like (Non-GC) types by immunohistochemical profiling. Previous studies showed better survival rate for the GCB groups. CD44 is necessary for tumor spread and metastasis and its expression is generally associated with unfavorable prognosis. We analyzed the expression and prognostic significance of standard isoform CD44s and its variant isoform CD44v6 in DLBCL types. Methods: Tissue microarray blocks were created from 52 nodal DLBCL with control tissue. Immunohistochemical staining for CD10, Bcl-6, MUM-1, CD44s, and CD44v6 were performed. The median follow-up period was 44 months. Results: Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl6+/MUM1+, n=17 (33%)] and non-GC subgroups [CD10-/Bcl6- or CD10-/Bcl6+/MUM1+, n=35 (67%)]. CD44s expression appeared more on non-GC cases of DLBCL (p=0.04). CD44s and CD44v6 did not result in any difference according to tumor stage, IPI scores, LDH levels. Upon survival analysis, CD44s and CD44v6 expression did not show any statistical correlation. Conclusions: CD44s expression may play a role during lymphomatogenesis of non-GC type DLBCL. No significant financial relationships to disclose.
Management of patients with ovarian cancer.
Authors: M H Tattersall, H J Solomon
Journal: Journal of Clinical Oncology (1986)

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.1986.4.4.612 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3514811 Management of patients with ovarian cancer. M H TattersallxM H TattersallSearch for articles by this author , H J SolomonxH J SolomonSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.4.612 First Page PDF © 1986 by American Society of Clinical Oncology
Practical Determination of the Site of the Anus Preternaturalis
Authors: W H BRUMMELKAMP
Journal: JAMA (1963)

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
Training psychotherapists to participate in psychotherapy outcome studies
Authors: M M Weissman, B J Rounsaville, E Chevron
Journal: American Journal of Psychiatry (1982)

The authors describe the issues involved in training experienced psychotherapists to participate in outcome studies. Potential areas of conflict among research goals, clinical goals, and therapists' expectations include the restrictions imposed by the research protocol, the therapists' feelings about being evaluated, and the restrictions of a defined psychotherapy. A training program that addresses these issues and an appropriate administrative structure can reduce these conflicts.
Abstract P2-05-12: Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in invasive breast cancer
Authors: N Yamashita, E Tokunaga, Y Inoue, K Tanaka, H Ueo, H Saeki, E Oki, Y Maehara
Journal: Cancer Research (2016)

Abstract Background: E-cadherin and vimentin are now regarded as major and conventional canonical markers of epithelial-mesenchymal transition (EMT). It is commonly assumed E-cadherin is uniformly lost during the process of EMT. We previously reported that the elevated expression of vimentin contributes to the aggressive phenotype in invasive breast cancer. On the other hand, the role of E-cadherin in breast cancer biology might be unclear and more complex. Although, cell cohesion during breast cancer invasion is often overlooked, accumulating evidences indicate breast tumor cells are typically cohesive and often display membrane-localized E-cadherin in both the primary tumor and distant metastases, termed collective invasion. Multiple mechanisms have emerged to address how epithelial breast tumors invade. Aims: The aim of this study is to reveal the clinical importance of the expression of E-cadherin and vimentin in breast cancer. Methods: The E-cadherin and vimentin protein expression were evaluated by immunohistochemistry (IHC) in 177 invasive breast cancer samples. Among these, E-cadherin and vimentin expression were evaluated in the set of primary breast cancer and metastatic lymph nodes in 65 cases. Results: The positive vimentin expression was highly correlated with poor disease-free survival (DFS) and overall survival (OS) (p=0.019 and p=0.0044), however, the E-cadherin expression alone did not correlate with prognosis. Interestingly, Both E-cadherin and vimentin positive tumor had the worst DFS and OS among all breast cancer (p=0.03 and p=0.0089). Vimentin expression was highly correlated between primary tumors and metastatic lymph nodes. However, E-cadherin expression levels were significantly elevated in metastatic lymph nodes (p=0.0017), Co-expression of E-cadherin and vimentin in the metastatic lymph nodes also showed worst DFS and OS (p=0.12 and p=0.027). Conclusions: Co-expression of E-cadherin and vimentin seems to be associated with the most aggressive phenotype and poorest prognosis in breast cancer, and positive E-cadherin expression may not always play roles for tumor suppression. Citation Format: Yamashita N, Tokunaga E, Inoue Y, Tanaka K, Ueo H, Saeki H, Oki E, Maehara Y. Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in invasive 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 P2-05-12.
Disease modifying drugs in rheumatoid arthritis
Authors: A Rahman, S Ahmed, M Underwood
Journal: BMJ (1997)

Rheumatoid arthritis (RA) is a systemic inflammatory disease whose major feature is a destructive peripheral polyarthritis. In this condition simple analgesics may relieve pain while non-steroidal anti-inflammatory drugs (NSAIDs) can reduce swelling and stiffness; neither however change the activity or rate of progression of the disease. 1 If these drugs fail to control symptoms, if there is radiological evidence of rapid or progressive joint damage, or if the patient has serious extra-articular manifestations of RA (e.g. lung disease, vasculitis, amyloidosis), it is usual to start a drug that might modify the disease or induce remission. This article discusses disease-modifying drugs (DMDs) and how to choose between them.
IKZF1 deletion is enriched in pediatric B-cell precursor acute lymphoblastic leukemia patients showing prednisolone resistance
Authors: T Imamura, M Yano, D Asai, A Moriya-Saito, S-I Suenobu, D Hasegawa, T Deguchi, Y Hashii, H Kawasaki, H Hori, K Yumura-Yagi, J Hara, K Horibe, A Sato
Journal: Leukemia (2016)
Prognostic significance of KRAS mutation rate in metastatic colorectal cancer patients
Authors: B. Vincenzi, C. Cremolini, A. Sartore-Bianchi, A. Russo, F. Mannavola, G. Perrone, F. Pantano, F. Loupakis, D. Rossini, E. Ongaro, E. Bonazzina, A. Zoccoli, G. De Maglio, G. Fontanini, A. Falcone, D. Santini, A. Onetti-Muda, S. Siena, G. Tonini, G. Aprile
Journal: Annals of Oncology (2015)
Abstract B28: BET bromodomain inhibitors antagonize Brd4-Mediator complexes to undermine the acute myeloid leukemia cell state
Authors: Anand S. Bhagwat, Jae-Seok Roe, Beverly A. Mok, Christopher R. Vakoc
Journal: Cancer Research (2016)

Abstract Acute myeloid leukemia (AML) is a hematologic malignancy with a 5-year survival rate of under 30%. We recently identified the bromodomain and extraterminal (BET) protein Brd4 as a therapeutic target in AML, and several trials are currently evaluating the clinical utility of BET inhibitors for this disease. BET inhibitors displace Brd4 from chromatin and subsequently reduce the expression of key oncogenes, such as Myc, leading to AML blast differentiation and cell death. However, the mechanism by which Brd4 maintains oncogene expression in AML is still unclear. We hypothesized that Brd4 functions by working with other coactivators in AML to promote expression of oncogenes. One such coactivator is the Mediator complex, which is comprised of ~30 subunits and directly contacts RNA Polymerase II to regulate its function. Initial purifications of Mediator from mammalian cells identified Brd4 as an associated factor. Using ChIP-seq analysis in AML cells, we show that Brd4 and Mediator closely co-localize across the genome. Moreover, chemical inhibition of Brd4 results in the displacement of Mediator from enhancer and promoter regions across the genome, an effect that occurrs within 30 minutes of treatment. While the genome-wide loss of Mediator occupancy is approximately 2-fold, a subset of promoters and enhancers exhibit dramatic loss of Mediator occupancy. Importantly, these regions are disproportionately associated with genes related to leukemia biology but only modestly overlap with super-enhancers. In addition, we show that shRNA-based knockdown of several Mediator subunits phenocopies the transcriptional and cellular effects of Brd4 inhibition without affecting levels of Brd4 in the cell. These effects include downregulation of Myc expression, induction of myeloid differentiation, and reduction of P-TEFb recruitment to chromatin. These findings support a model in which Brd4 functions in concert with the Mediator complex to maintain oncogenic gene expression programs in leukemia and shed light on the mechanisms of action underlying a promising new class of therapeutics for AML. Citation Format: Anand S. Bhagwat, Jae-Seok Roe, Beverly A. Mok, Christopher R. Vakoc. BET bromodomain inhibitors antagonize Brd4-Mediator complexes to undermine the acute myeloid leukemia cell state. [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 B28.
Safe and Immunocompatible Nanocarriers Cloaked in RBC Membranes for Drug Delivery to Treat Solid Tumors
Authors: Brian T. Luk, Ronnie H. Fang, Che-Ming J. Hu, Jonathan A. Copp, Soracha Thamphiwatana, Diana Dehaini, Weiwei Gao, Kang Zhang, Shulin Li, Liangfang Zhang
Journal: Theranostics (2016)

The therapeutic potential of nanoparticle-based drug carriers depends largely on their ability to evade the host immune system while delivering their cargo safely to the site of action. Of particular interest are simple strategies for the functionalization of nanoparticle surfaces that are both inherently safe and can also bestow immunoevasive properties, allowing for extended blood circulation times. Here, we evaluated a recently reported cell membrane-coated nanoparticle platform as a drug delivery vehicle for the treatment of a murine model of lymphoma. These biomimetic nanoparticles, consisting of a biodegradable polymeric material cloaked with natural red blood cell membrane, were shown to efficiently deliver a model chemotherapeutic, doxorubicin, to solid tumor sites for significantly increased tumor growth inhibition compared with conventional free drug treatment. Importantly, the nanoparticles also showed excellent immunocompatibility as well as an advantageous safety profile compared with the free drug, making them attractive for potential translation. This study demonstrates the promise of using a biomembrane-coating approach as the basis for the design of functional, safe, and immunocompatible nanocarriers for cancer drug delivery.
The state of the society: a year of continued growth.
Authors: R J Mayer
Journal: Journal of Clinical Oncology (1998)

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.1998.16.9.3192 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9738591 The state of the society: a year of continued growth. R J MayerxR J MayerSearch for articles by this author Show More Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. https://doi.org/10.1200/JCO.1998.16.9.3192 First Page PDF © 1998 by American Society of Clinical Oncology
Bibliography of the History of Medicine of the United States and Canada, 1939-1960.
Journal: Annals of Internal Medicine (1965)

Book Reviews to Danville for her operation.As he made the incision, he found her abdomen bruised from the pommel of the saddle.Five days later he found her making her own bed and twenty days later she remounted her horse and rode back the sixty miles through the woods to Greenburg and survived her surgeon by twelve years.The stories are intensely interesting and completely honest and authentic.Particu- larly interesting is the account of Warren's first experience in 1846 with ether anaes- thesia.Sim's struggle to cure the poor slave girl Lucy with her huge vesico-vaginal fistula makes a fascinating and heroic story as does Murphy's first arterial anastomosis in 1896.It is altogether one of the most readable and absorbing books ever produced, and illustrates the great contribution of American Surgery to the good of mankind.
STING contributes to anti-glioma immunity via triggering type-I IFN signals in the tumor microenvironment
Authors: Takayuki Ohkuri, Arundhati Ghosh, Akemi Kosaka, Jianzhong Zhu, Maki Ikeura, Michael David, Simon C Watkins, Saumendra N Sarkar, Hideho Okada
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts While type-I interferons (IFNs) play critical roles in antiviral and antitumor activity, it remains to be elucidated how type-I IFNs are produced in sterile conditions of the tumor microenvironment and directly impacts tumor-infiltrating immune cells. We report that both human and
Abstract IA11: Deciphering the immunobiology of ovarian cancer to create effective immunotherapy.
Authors: Daniel J. Powell
Journal: Clinical Cancer Research (2016)

Abstract Deep interrogations of the immunological landscape of human ovarian cancer has revealed the importance of the immune system in tumor control. In particular, the finding that intratumoral accumulation of tumor-infiltrating lymphocytes (TILs) is associated with improved survival in ovarian and various other cancer types supports the notions that spontaneously-arising T-cells with antitumor activity reside in cancer and control tumor outgrowth, and that this prognostic biomarker can be reinforced though administration of immunotherapy. Since this association was first described more than a decade ago, more sophisticated analyses have refined our understanding of the complex interplay between ovarian cancer cells and the host immune system. This includes the recent elucidation of a phenotypically-defined subset of ovarian cancer associated TILs that exhibit specific reactivity against autologous tumor cells, which represent a potential source for tumor-reactive T cell for use in the adoptive immunotherapy of ovarian cancer. Additionally, the discovery that the antigenic repertoire recognized by TILs is comprised of both shared tumor associated antigens and patient specific neo-antigens derived from mutated self-proteins uniquely expressed by the ovarian cancer cell has rationalized the clinical testing of highly personalized vaccines. While induction of patient-specific T cell responses holds significant promise, further analysis has revealed that the ovarian cancer microenvironment harbors a myriad of immunosuppressive factors that have the potential to thwart otherwise effective T cell responses. Ovarian cancer cells downregulate the expression of molecules associated with immune recognition and preferentially recruit inhibitory cells such as regulatory T cells to the tumor site. Ovarian cancer cells also express multiple negative immunoregulatory ligands that interact with reciprocal receptors expressed preferentially by the subset of tumor-reactive T cells and thereby limit their activity, however, with a new cadre of antibodies that effective block these axes of immunosuppression, clinical trials are underway to determine the efficacy of this form of passive immunomodulation and encouraging results are emerging. Taken together, detailed exploration of the immunobiology of the ovarian cancer microenvironment has increased our understanding of the roles of the cellular and molecular elements that influence tumor outgrowth. This knowledge serves as a roadmap for the rational development of effective immunotherapeutic approaches in ovarian cancer. Citation Format: Daniel J. Powell, Jr. Deciphering the immunobiology of ovarian cancer to create effective immunotherapy. [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 IA11.
Impact of p53, p21 and cell cycle check points in the response of pancreatic tumors to temozolomide and O6-Benzylguanine
Authors: Sathish Kumar Sabapathi, Seema Gupta, Xiaoyan Liu, Mansoor M. Ahmed, Demetrius M. Kokkinakis
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1378 

Pancreatic tumors are refractive to DNA alkylating agents due to their high O6-methylguanine-DNA methyltransferase (MGMT) activity. An impressive enhancement in the efficacy of carmustine (BCNU) and temozolomide (TMZ) has been demonstrated in p53 efficient human pancreatic tumor xenografts following inactivation of MGMT with O6-benzylguanine (BG). Here we report that mutant-p53 cell lines are markedly more resistant than wt-p53 cell lines to treatment with TMZ in the presence of BG and that induction of a p53 dependent G1/S followed by a p53 independent G2/M cell cycle arrest in response to TMZ induced DNA damage correlates with enhanced apoptosis. Accordingly, we postulate that the induction of p53/p21 dependent cell cycle arrest by TMZ and concomitant preservation of O6-methylguanine (O6MeG) adducts by continuous depression of MGMT levels are prerequisites for an optimal apoptotic response. In support of the above, we have determined that levels of p53, nuclear p21, BAX and BCL-2 proteins remain unchanged following treatment of the mut-p53 Capan-1 or MEF (p53 -/-) lines with TMZ plus BG. This contrasts with the response of Capan-2 and MEF(p53 +/+, +/−) lines to TMZ plus BG, where marked induction of p53, p21 and BAX correlate with a 5 fold increase in apoptosis over that observed in p53 deficient lines. Of significant importance in the toxicity of TMZ for p53 efficient lines is the early induction of the mismatch repair (MMR) proteins PMS 1 and 2 and MLH 1, which participate in the abortive repair of O6-MeG mismatches and the subsequent cell killing. The induction of these proteins and their expected contribution to the efficacy of MMR related toxicity may be additive to the early apoptotic response related to the p53 mediated G1/S arrest. The above demonstrate that p53/p21 induced cell cycle arrest not only induces a classic proapoptotic response by blocking G1/S progression, but it also may facilitate cell killing by upregulating the MMR response.