tbuckley/cabot-search huggingface dataset:
Abstract 5121: Immunomodulating cytokine profiling of docetaxel-treated human prostate cancer specimens
Authors: Debapriya G. Mehrotra, Nilesh Brijwani, Biplab Tewary, Vasathkumar Sekar, Abhishek Krishnan, Dency D. Pinto, Muthusamy Oliyarasi, Biswanath Majumder, Saravanan Thiyagarajan, Padhma Radhakrishnan, Pradip K. Majumder
Journal: Cancer Research (2016)

Abstract Prostate cancer is one of the leading malignancies in adult males worldwide and existing therapies often result in treatment failure and emergence of castration resistant prostate cancer (CRPC). Outcome of some recent clinical trials highlighted the benefit of Docetaxel as a part of initial therapy in CRPC. However, a significant number of patients still remain chemoresistant. Context dependent response profiling using a clinically oriented functional platform would further improve this scenario. Here, we elucidated the role of different immune cells and type 1 and type 2 cytokines in improving Docetaxel sensitivity to prostatic carcinoma. We tested Docetaxel sensitivity in prostate tumors (n = 10) using CANScriptTM platform, a personalized next generation functional testing tool (Majumder B et al. Nat. Commun 2015, Goldman A et al. Nat. Commun. 2015). Of these 10 tumors, 4 were found to be sensitive to Docetaxel and 6 were insensitive. The immune profiling of these tumors suggested that despite preferential CD45, CD8 and CD4 levels in majority of the responders both responders and non responders display modest numbers at baseline. We also observed similar heterogeneity in CD69 (T cell activation marker) in these two groups. Altered expression of cytokines was observed in Docetaxel sensitive and resistant tumors upon their co-culture with peripheral blood mononuclear cells (PBMC), suggesting a defined role of these cytokines in Docetaxel response. We extended the study further by testing the efficacy of PD-1/ PD-L1 inhibitors in Docetaxel resistant tumors. Our results provide the basis for validation of immune phenotypes and cytokines as therapeutic response biomarkers in Docetaxel treated prostatic tumors. 1. Majumder B et al. Nat. Commun.6:6169 (2015). 2. Goldman A et al. Nat. Commun. 6:6139 (2015). Citation Format: Debapriya G. Mehrotra, Nilesh Brijwani, Biplab Tewary, Vasathkumar Sekar, Abhishek Krishnan, Dency D. Pinto, Muthusamy Oliyarasi, Biswanath Majumder, Saravanan Thiyagarajan, Padhma Radhakrishnan, Pradip K. Majumder. Immunomodulating cytokine profiling of docetaxel-treated human prostate cancer specimens. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5121.
A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia
Authors: Daniel A. Lichtenstein, Andrew W. Crispin, Anoop K. Sendamarai, Dean R. Campagna, Klaus Schmitz-Abe, Cristovao M. Sousa, Martin D. Kafina, Paul J. Schmidt, Charlotte M. Niemeyer, John Porter, Alison May, Mrinal M. Patnaik, Matthew M. Heeney, Alec Kimmelman, Sylvia S. Bottomley, Barry H. Paw, Kyriacos Markianos, Mark D. Fleming
Journal: Blood (2016)
Annual screening for prostate cancer did not reduce mortality from prostate cancer
Authors: Steven E Canfield
Journal: Annals of Internal Medicine (2009)

ACP Journal Club16 June 2009Annual screening for prostate cancer did not reduce mortality from prostate cancerSteven E. Canfield, MDSteven E. Canfield, MDUniversity of Texas Medical School at Houston, Houston, Texas, USA (S.E.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-12-200906160-02004 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationAndriole GL, Crawford ED, Grubb RL 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310-9. https://pubmed.ncbi.nlm.nih.gov/19297565Clinical Impact RatingsGIM/FP/GP: Oncology: References1 Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤ 4.0 ng per milliliter. N Engl J Med. 2004;350:2239-46. [PMID: 15163773] Google Scholar2 Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71-96. [PMID: 18287387] Google Scholar3 Johansson JE, Andrén O, Andersson SO, et al. Natural history of early, localized prostate cancer. JAMA. 2004;291:2713-9. [PMID: 15187052] Google Scholar4 Draisma G, Boer R, Otto SJ, et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst. 2003;95:868-78. [PMID: 12813170] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Medical School at Houston, Houston, Texas, USA (S.E.C.)This article was published at Annals.org on 2 June 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPeriodic screening with prostate-specific antigen testing reduced mortality from prostate cancer Steven E. Canfield Metrics 16 June 2009Volume 150, Issue 12Page: JC6-4KeywordsAntigensCancer screeningCancer treatmentDigital rectal examinationForecastingLikelihood ratioLung and intrathoracic tumorsMortalityProstate cancerRelative risk ePublished: 16 June 2009 Issue Published: 16 June 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 2961: deBouganin conjugated to trastuzumab overcomes multiple mechanisms of T-DM1 drug resistance
Authors: Rachelle L. Dillon, Shilpa Chooniedass, Arjune Premsukh, Gregory P. Adams, Joycelyn Entwistle, Glen C. MacDonald, Jeannick Cizeau
Journal: Cancer Research (2016)

Abstract DeBouganin is a T-cell epitope-depleted variant of the type I Ribosome Inactivating Protein (RIP) plant toxin Bouganin. DeBouganin binds and deadenylates the sarcin/ricin loop of the 28S subunit of the ribosomal RNA leading to protein synthesis inhibition and apoptosis. To demonstrate the potential advantages of deBouganin over current small molecule payloads, deBouganin was randomly chemically conjugated to trastuzumab with a DAR of approximately 2 and compared to T-DM1 both in vitro and in vivo. The trastuzumab-deBouganin conjugate (T-deB) demonstrated a tighter IC50 range of killing and an overall greater potency in vitro against most cells lines with high levels of Her2 expression as compared to T-DM1. In addition, unlike T-DM1, T-deB was unaffected by inhibitors of multidrug resistance (MDR) and overexpression of Bcl-2 family members. Moreover, T-deB potency was unchanged by Her2-Her3 dimerization in the presence of heregulin. Contrary to T-DM1 which showed only minimal cytotoxicity, T-deB was highly potent in vitro against tumor cells with cancer stem cell (CSC) properties by preventing the formation of tumorspheres. Furthermore, in a BT-474 xenograft study, T-deB was more efficacious than T-DM1 resulting in increased survival of the T-deB treated mice. Overall, the results demonstrate the potency and efficacy of deBouganin and emphasize the importance of using payloads with different MOAs. The data suggest that deBouganin used alone or in combination with other payloads could be a highly effective cancer therapeutic that would provide prolonged clinical benefit. Citation Format: Rachelle L. Dillon, Shilpa Chooniedass, Arjune Premsukh, Gregory P. Adams, Joycelyn Entwistle, Glen C. MacDonald, Jeannick Cizeau. deBouganin conjugated to trastuzumab overcomes multiple mechanisms of T-DM1 drug resistance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2961.
Abstract 5261: Novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1 and VEGF expressions and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model
Authors: Dong Hwan Kim, Min Jeong Kim, Bokyung Sung, Yong Jung Kang, Seong Yeon Hwang, Na Lam Hwang, Nam Deuk Kim
Journal: Cancer Research (2016)

Abstract Taking phytochemicals provide various benefits for human health. Among them, resveratrol, from the blueberry, is well known for its beneficial effects for human. However, resveratrol has photosensitive and easily decomposition by digestive enzyme. Thus we synthesized several synthetic analogues of resveratrol with potent activity. One of them, 4-(6-hydroxy-2-naphtyl)-1, 3-benzenediol (HS-1793) treatment showed potent antitumor activity in various human cancer cells. In this study, we investigated the effects of a novel analogue of resveratrol, HS-1793 on the expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in MCF-7 with MDA-MB-231 human breast cancer cells. We found that HS-1793 inhibited hypoxia (1.0% oxygen) induced HIF-1α protein level and its downstream target, vascular endothelial growth factor (VEGF) expression dose-dependently in both cell lines. Decreased HIF-1α by HS-1793 modulated through 26S proteasome pathway. We also found that HS-1793 suppressed tumor growth in tumor xenograft mice model. Treatment with 10 mg/kg of HS-1793 suppressed Ki-67 and CD31 expressions in tumor tissues. Above all, HS-1793 shows more powerful effects than resveratrol. Taken together, these results implied that HS-1793, a novel analogue of resveratrol might be a new potent chemopreventive agent and anticancer therapy in human breast cancer. Citation Format: Dong Hwan Kim, Min Jeong Kim, Bokyung Sung, Yong Jung Kang, Seong Yeon Hwang, Na Lam Hwang, Nam Deuk Kim. Novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1 and VEGF expressions and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5261.
Differences in sexual practices and their role in gender, age, and racial disparities in HPV-positive HNSCC.
Authors: Carole Fakhry, Kevin J. Cullen, Janice Bowie, Roland Thorpe, Gypsyamber D'Souza
Journal: Journal of Clinical Oncology (2013)

6032 Background: Human papillomavirus associated head and neck cancers (HPV-HNC) have been steadily rising in the U.S., while HPV-unassociated HNCs have declined due to reductions in tobacco use. The trend of increasing HPV-HNC has been attributed to the sexual revolution, but not well explored. Individuals with HPV-HNC tend to be younger, white, and male and HPV-HNC is strongly associated with sexual behaviors. Methods: This analysis included 2270 men and 2261 womenfrom the 2009-10 National Health and Nutrition Examination Survey (NHANES) who answered a survey on demographic and behavioral risk factors. Participants also provided an oral rinse and gargle sample for HPV DNA analysis. Prevalence of sexual behaviors and oral HPV infection were calculated by gender, age cohort (18-29, 30-44, 45-59, 60-69), and race using NHANES samples weights to provide unbiasedestimates for the US population. Results: Men (85%) and women (83%) were similarly likely to have ever performed oral sex, but men had more lifetime oral and vaginal sexual partners and higher oral HPV16 prevalence (each p&lt;0.001).Ever having performed oral sex was less common among 60-69 than 30-44 year old men (74% vs. 92%, p&lt;0.001) and women (71% vs. 91%, p&lt;0.001). Older individuals also had less lifetime sexual partners, but marginally higher oral HPV16 prevalence. Whites were more likely than blacks (90%vs69%, p&lt;0.001) to have ever performed oral sex, to have more lifetime oral sex partners and higheroral HPV16 prevalence(each p&lt;0.001). Prevalence ratios of ever performing oral sex for men vs. women (PR=1.03), 45-59 vs 60-69 year olds(PR=1.25), and whites compared to blacks (PR=1.32) were modest relative to more striking prevalence ratios for oral HPV infection andHPV-HNC(each PR&gt;1.5). Conclusions: There are significant gender, age-cohort, and racial differences in oral sexual practices in a representative sample of the U.S population. Although men, younger age-cohorts, and whites have higher exposures to sexual behaviors of interest, the magnitude of these behavioral differences does not appear large enough to explain the observed disparities in oral HPV infection and HPV-HNC.
Abstract 2056: Development of quaternary amine linkers for ADCs: Application to auristatin E and tubulysin
Authors: Patrick J. Burke, Joseph Z. Hamilton, Thomas A. Pires, Jocelyn R. Setter, Joshua H. Hunter, Julia H. Cochran, Brian E. Toki, Peter D. Senter, Robert P. Lyon, Scott C. Jeffrey
Journal: Cancer Research (2016)

Abstract The recent clinical success of antibody-drug conjugates (ADCs) has spawned an increased effort to identify new technologies, and the development of new drug-linker chemistry is vital to expand the scope of conjugatable payloads. The tertiary amine functional group is a common structural motif present in many bioactive compounds, including antimitotics of the auristatin and tubulysin classes. Traditionally, conjugation of tertiary amines required drug derivatization or modification to remove an N-alkyl group, thus creating a readily conjugatable secondary amine. However, identifying appropriate modifications that do not compromise the activity of the drug is frequently time consuming and often unsuccessful. To eliminate the need for such structural modifications, we sought a method for stable conjugation and facile release through the tertiary amine functional group by creating linkers with a quaternary amine point of attachment. To validate the linker strategy, quaternary amine-based cleavable linkers bearing auristatin E were synthesized and evaluated as ADCs. The conjugates were stable in rodent plasma, and were potent and immunologically specific both in vitro and in vivo in a Hodgkin lymphoma xenograft model. A second application of this technology has been demonstrated with tubulysins, another class of potent antimitotics containing a tertiary amine at the N-terminus. A cleavable quaternary amine linker containing a tubulysin analog was synthesized and ADCs were prepared and evaluated. The tubulysin conjugates were potent and immunologically specific across a panel of cancer cell lines, including multiple MDR-positive lines. Furthermore, the tubulysin conjugate displayed ‘bystander activity’ in an in vitro co-culture assay. The quaternary amine linkers represent an advance in linker technology and will enable the evaluation of drug classes previously inaccessible as ADCs. Citation Format: Patrick J. Burke, Joseph Z. Hamilton, Thomas A. Pires, Jocelyn R. Setter, Joshua H. Hunter, Julia H. Cochran, Brian E. Toki, Peter D. Senter, Robert P. Lyon, Scott C. Jeffrey. Development of quaternary amine linkers for ADCs: Application to auristatin E and tubulysin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2056.
Activation of B-Cell Maturation Antigen (BCMA) on Human Multiple Myeloma Cells by a Proliferation-Inducing Ligand (APRIL) Promotes Myeloma Cell Function in the Bone Marrow Microenvironment.
Authors: Merav Leiba, Jiangchun Xu, Weihua Song, Xian-Feng Li, Peter Burger, Jennifer Kordich, Linda Cassiano, Klaus Podar, Dharminder Chauhan, Teru Hideshima, Nikhil C. Munshi, Paul Richardson, Kenneth C. Anderson, Yu-Tzu Tai
Journal: Blood (2007)
Histological transformation to diffuse large B-cell lymphoma in patients with Waldenström macroglobulinemia
Authors: Jorge J. Castillo, Joshua Gustine, Kirsten Meid, Toni Dubeau, Zachary R. Hunter, Steven P. Treon
Journal: American Journal of Hematology (2016)

Histological transformation to diffuse large B‐cell lymphoma (DLBCL) rarely occurs in patients with Waldenström Macroglobulinemia (WM). We identified 20 patients out of a cohort of 1,466 WM patients who experienced histologic transformation. The 5, 10, and 15‐year cumulative incidence rates were 1, 2.4, and 3.8%, respectively. Approximately half of the patients were naive to nucleoside analogues, and a quarter were previously untreated for WM at the time of transformation. More than 80% of patients presented with extranodal involvement, 65% with high IPI scores. DLBCL cells did not express CD10 but expressed BCL6 and BCL2. All patients were treated with chemoimmunotherapy. The median survival from histological transformation was 2.7 years. The median overall survival was shorter for transformed patients versus those who did not transform (estimated 9 vs. 16 years; P = 0.09). Histological transformation to DLBCL is rare, and is associated with inferior survival in WM. Am. J. Hematol. 91:1032–1035, 2016. © 2016 Wiley Periodicals, Inc.
IMPACT of Therapeutic Strategy and Time to Therapy Initiation on Clinical Evolution of Patients with NEWLY Diagnosed Chronic Myelomonocytic Leukemia. a Report from Erasme Study
Authors: Brayan Marcel Merchan Ruiz, Teresa Bernal, Montserrat Arnan, Mar Tormo, Jose Angel Hernandez Rivas, Maria Calbacho, Rosa Coll, Rafael Romero, Andres Insunza, Joan Bargay, David Valcarcel, Montse Rafel, Regina Garcia
Journal: Blood (2014)
Shared decision-making tools for patients with hematologic malignancies.
Authors: Thomas William LeBlanc, David Rizzieri, Peter Martin, Valerie Mayorga, Katie Deering, Brad Schenkel
Journal: Journal of Clinical Oncology (2016)

e19007 Background: Shared decision-making (SDM) empowers patients to take more responsibility for their health care while ensuring a patient is fully informed of their treatment options. Patient decision aids (PDAs) following criteria set forth by the International Patient Decision Aid Standards (IPDAS) Collaboration have been shown to improve the quality of care delivered and health outcomes. The objective of this project was to develop two patient-centered decision aids to enable previously treated chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients to make an informed treatment decision in collaboration with their healthcare provider (HCP). Methods:: Both PDA development processes followed the IPDAS model which includes: determining the content and design; development of a prototype and testing with patients to check comprehensibility and acceptability; field testing the final version with patients and HCPs to assess usability; and production of a final version. In addition, multidisciplinary advisory committees were formed with four HCPs and a CLL/MCL patient to guide the development and evaluation of the PDAs. Results: During the content development process, interviewed patients and HCPs thought patients should be involved in treatment decisions and preferred an online PDA. Patients identified efficacy, quality of life, and dosing schedule as their foremost decision drivers. HCPs felt patients’ foremost decision drivers were quality of life, toxicity, and efficacy. Based on feedback, online prototypes were designed with patient-friendly graphics and audio. Direct patient feedback on the PDAs showed that patients thought they were helpful and informative. In response to testing, language was incorporated into the final PDAs highlighting that each treatment is not right for every patient and every patient responds differently. The final PDAs discuss and present evidence about the risks and benefits of different treatment options helping patients weigh available evidence along with their individual preferences and values. Conclusions: Guided by the IPDAS model, both PDAs will facilitate quality decision-making and be valuable SDM tools for patients with previously treated CLL/MCL and their HCPs.
Jak1–STAT3 Signals Are Essential Effectors of the USP6/TRE17 Oncogene in Tumorigenesis
Authors: Laura Quick, Robert Young, Ian C. Henrich, Xiaoke Wang, Yan W. Asmann, Andre M. Oliveira, Margaret M. Chou
Journal: Cancer Research (2016)

Abstract Bone and soft tissue tumors (BSTT) are relatively poorly understood, hampering the development of effective therapies. Here we report a critical effector pathway for the ubiquitin-specific protease 6 (USP6)/TRE17 oncogene, which is overexpressed upon chromosome translocation in various human tumors, including aneurysmal bone cyst (ABC) and the related benign lesion nodular fasciitis. Ectopic expression of USP6 is known to drive formation of tumors, which recapitulate key features of ABC and nodular fasciitis; however, the identity of USP6′s relevant substrates has been obscure. Here we report that the Jak1–STAT3 signaling pathway serves as an essential effector of USP6 in BSTT formation. We found that USP6 directly deubiquitinated Jak1, leading to its stabilization and activation of STAT3. The tumorigenic potential of USP6 was attenuated significantly by CRISPR-mediated deletion of Jak1 or STAT3, or by administration of a Jak family inhibitor. Analysis of primary clinical samples of nodular fasciitis confirmed the activation of a Jak1–STAT3 gene signature in vivo. Together, our studies highlight Jak1 as the first identified substrate for USP6, and they offer a mechanistic rationale for the clinical investigation of Jak and STAT3 inhibitors as therapeutics for the treatment of bone and soft tissue tumors along with other neoplasms driven by USP6 overexpression. Cancer Res; 76(18); 5337–47. ©2016 AACR.
Abstract 2676: Epithelial-mesenchymal transition does not require transcriptional repression of the epithelial program <i>in vivo</i>
Authors: Nicole M. Aiello, David Balli, Robert Norgard, Jinyang Li, Amine Sahmoud, Ben Z. Stanger
Journal: Cancer Research (2016)

Abstract Epithelial-mesenchymal transition (EMT), the process by which an epithelial cell loses its adhesion to neighboring cells and acquires a motile, fibroblast-like phenotype, is critical for many aspects of embryogenesis and has been strongly implicated in tumor cell invasion and metastasis. EMT is thought to be primarily regulated at the transcriptional level through repression of epithelial genes by transcription factors such as Snail, Zeb and Twist. To date, the mechanisms driving EMT have been parsed out almost exclusively in vitro under pre-defined conditions (ie, using TGFβ as an EMT inducer), but it remains to be seen whether the machinery that regulates in vitro EMT is physiologically relevant. Using a lineage labeled mouse model of pancreatic ductal adenocarcinoma (PDAC), we isolated tumor cells that have spontaneously undergone EMT to interrogate the molecular mechanisms driving this process in vivo. By comparing the transcriptomes of epithelial (E-cadherin+) and mesenchymal (E-cadherin-) tumor cells, we found that for a majority of PDAC tumors, EMT does not require transcriptional repression of the epithelial program. These cells were fully capable of upregulating a mesenchymal program, as evidenced by the increased expression of collagens, SPARC, MMP2, PDPN, and PRRX1; however, despite the loss of E-cadherin protein, we detected no change in transcript levels of E-cadherin or other epithelial genes after EMT. Our results suggest that in vivo, cells that undergo EMT retain epithelial gene transcription, which may confer the ability to rapidly oscillate between epithelial and mesenchymal states. Citation Format: Nicole M. Aiello, David Balli, Robert Norgard, Jinyang Li, Amine Sahmoud, Ben Z. Stanger. Epithelial-mesenchymal transition does not require transcriptional repression of the epithelial program in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2676.
Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis
Authors: Junjuan Wang, Jiaqiu Wang, Ping Lu, Youzhi Cai, Yafei Wang, Lan Hong, Hao Ren, Boon Chin Heng, Hua Liu, Jing Zhou, Hongwei Ouyang
Journal: Biomaterials (2015)