tbuckley/cabot-search huggingface dataset:
Le paludisme en Autriche de 1990 à 2000
Authors: R Strauss, C Pfeifer
Journal: Eurosurveillance (2003)

En Autriche, de 1990 a 2000, 924 cas de paludisme lies aux voyages ont ete notifies (moyenne = 84/an), sans tendance significative a la baisse ou a la hausse. La majorite des cas etaient infectes par P. falciparum (n = 517; 55,9%) suivi de P. vivax ou ovale (n = 321; 34,7%) et P. malariae (n = 29; 2,2%). Les infections ont ete contractees lors d'un voyage dans des regions fortement impaludees (n = 686; 74,2%), les etats federaux les plus peuples rapportant le plus grand nombre de cas : Vienne (n = 336, 36,4%), Styrie (n = 156, 16,8%) et Basse-Autriche (n = 151, 16,3%). Douze deces ont ete notifies, principalement lies a P.falciparum (n = 9,75%; taux de letalite : 1,9%). Les donnees sur la chimioprophylaxie etaient disponibles pour 752 cas (81,4%) mais seuls la moitie ont fourni des details sur les medicaments pris (n=367, 48,8%). Les donnees sur l'observance etaient disponibles pour 45,4% des cas et seuls 60% avaient entierement suivi le traitement prophylactique.
Abstract 1352: High-throughput matrix screening reveals synergistic chemotherapeutic combinations with blockade of CD47 to enhance cytotoxicity in breast cancer
Authors: David D. Roberts, Ashley Smith, John M. Sipes, Adam Wilson, Lesley Mathews-Griner, Rajarshi Guha, Craig J. Thomas, Marc Ferrer, David R. Soto-Pantoja
Journal: Cancer Research (2016)

Abstract CD47 is a widely expressed cell surface receptor that serves as a counter-receptor for SIRPα in recognition of self by the innate immune system. On the other hand CD47 also serves as a signaling receptor for the matricellular protein thrombospondin-1 (TSP-1), regulating cell growth and survival. Clinical studies consistently show that increased expression of CD47 is an independent poor prognosis factor in several types of cancer, including breast cancer. Moreover elevated expression of CD47 is associated with development of resistance to chemotherapy by inhibiting cell death pathways. Therefore, agents targeting CD47 are attractive to overcome therapeutic resistance in breast cancer. Using a high-throughput assay in a 1536-well microplate format we screened a comprehensive set of approved and late stage development oncology drugs in combination with an anti-CD47 morpholino to find combinatorial strategies that are more cytotoxic against breast cancer cells. Potency and efficacy measurements during the primary screen identified compounds that synergized with anti-CD47 to augment their cytotoxicity effect. One of the compound groups that demonstrated increased synergism with CD47 were the anthracycline family of drugs. We further validated these results in a syngeneic model of breast cancer and demonstrated that blockade of CD47 in combination with doxorubicin improves chemotherapeutic response when compared to mice administered doxorubicin alone. Furthermore the anti-tumor response with anti-CD47 combination is associated with a reduction in glycolytic flux and a selective up regulation of mitophagy. Overall this indicates that blockade of CD47 in the clinic may synergize with chemotherapeutic strategies to improve patient curative responses. Citation Format: David D. Roberts, Ashley Smith, John M. Sipes, Adam Wilson, Lesley Mathews-Griner, Rajarshi Guha, Craig J. Thomas, Marc Ferrer, David R. Soto-Pantoja. High-throughput matrix screening reveals synergistic chemotherapeutic combinations with blockade of CD47 to enhance cytotoxicity in breast cancer. [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 1352.
Prognostic indicators for survival in head and neck squamous cell carcinomas: Analysis of a series of 651 cases and implication in the development of new therapeutic strategies
Authors: C. Le Tourneau, M. Velten, G.-M. Jung, G. Bronner, H. Flesch, C. Borel
Journal: Journal of Clinical Oncology (2004)

5551 Background: Whereas there is increasing interest in adjuvant radio-chemotherapy in head and neck squamous cell carcinomas (HNSCC), the prognostic indicators which allow the therapeutic indications to be established are not yet clearly defined. Thus, we decided to study the influence of pT stage, pN stage, tumor volume and number of lymph nodes invaded on survival of HNSCC in order to improve therapeutic indications. Methods: In this retrospective survival study, 651 patients who were operated on for HNSCC by the same surgical team between 1990 and 1997 and who underwent lymph node clearance were included. The site of the primary cancer was the buccal cavity (109), the oropharynx (291), the larynx (70) and the hypopharynx (181). 445 patients who had lymph node metastases, diseased resection margins or a tumour of large size received adjuvant radiotherapy. Results: From a univariate analysis of overall survival, the statistically significant prognostic histological indicators were the pT stage (p<0.0001), the pN stage (p<0.0001), capsule rupture (p<0.0001), the number of lymph nodes invaded (0, 1–3, 4–9, =10) (p<0.0001) and the total tumor volume (=5, 5–20, 20–50, >50 cm3) (p<0.0001). Cox survival models after adjusting for age, sex, and site of the primary cancer found the independent statistically significant prognostic indicators for overall survival to be pT stage (p<0.0001), pN stage (p<0.0001) and the total tumor volume (p<0.04). When, instead of the pN stage, the number of lymph nodes invaded was considered, it emerged as a statistically independent prognostic indicator. Conclusions: pT and pN stages but also the number of lymph nodes invaded and total tumor volume should be considered as essential prognostic indicators and any clinical trial developed in this field should stratify accordingly. No significant financial relationships to disclose.
Outcomes in Adolescents and Young Adults (AYA) with Hodgkin Lymphoma (HL) Treated on US Cooperative Group Protocols: An Adult Intergroup (E2496) and Children's Oncology Group (COG AHOD0031) Comparative Analysis
Authors: Tara O Henderson, Susan K Parsons, Kristen Wroblewski, Lu Chen, Fangxin Hong, Sonali M. Smith, Jennifer McNeer, Ranjana Advani, Randy D. Gascoyne, Louis Constine, Sandra J Horning, Nancy L Bartlett, Bijal D. Shah, Joseph M. Connors, John P. Leonard, Brad S. Kahl, Kara M. Kelly, Cindy Schwartz, Debra L. Friedman, Leo I. Gordon, Andrew M. Evens
Journal: Blood (2015)
Abstract 1581: Crosstalk of androgen sensitive prostate cancer cells and insensitive prostate cancer cells
Authors: Yuta Takezawa, Atsushi Mizokami, Kazuaki Machioka, Kouji Izumi, Hiroaki Iwamoto, Maolake Aerken, Natsagdorg Ariunbold, Mikio Namiki
Journal: Cancer Research (2016)

Abstract [Background] The mechanisms that prostate cancer (PCa) progresses to castration-resistant PCa (CRPC) are adaptation and clonal selection. We hypothesized that PCa proliferated while each mechanism cooperated when PCa recurred. [Materials and Methods] After LNCaP cells were transfected with luciferase reporter driven by PSA promoter, LNCaP were cocultured with androgen-insensitive DU145 or PC-3. Then DHEA or DHT were added to the medium and luciferase assay was performed. Also, we added DHEA or DHT in the medium and measured various androgens level by LC-MS/MS. As for proliferation, LNCaP were cocultured with DU145 or PC -3 in 2-layer chamber and number of LNCaP were counted. DU145 and PC-3 were also cocultured with LNCaP cells for 4 days. We also checked migration by using 2-layer chamber and migrated cells were counted. [Results] Whereas DHEA was converted into DHT in DU145 and induced PSA promoter activity in LNCaP, the effect was not found in PC-3. Moreover, DU145 elevated DHT-induced PSA promoter activity. DU145 promoted LNCaP proliferation stimulated by DHT and DHEA, but PC-3 did not. LNCaP also promoted proliferation of DU145 and PC-3. LNCaP promoted migration of PC-3, but not DU145. [Conclusion] Cross-talk between androgen-sensitive PCa cells and androgen-insensitive PCa cells might regulate progression of CRPC. Citation Format: Yuta Takezawa, Atsushi Mizokami, Kazuaki Machioka, Kouji Izumi, Hiroaki Iwamoto, Maolake Aerken, Natsagdorg Ariunbold, Mikio Namiki. Crosstalk of androgen sensitive prostate cancer cells and insensitive prostate cancer cells. [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 1581.
Abstract 1756: Marijuana use and serum testosterone concentrations among U.S. males
Authors: Katherine A. McGlynn
Journal: Cancer Research (2016)

Abstract Background: Testicular germ cell tumors (TGCT) of young men can be histologically divided into nonseminomas and seminomas. Although TGCTs are thought to be hormonally-related, very few risk factors have been identified. Recently, however, marijuana use has been linked to risk of nonseminoma, which has peak incidence at a younger age (25 years) than does seminoma (35 years). Whether marijuana may be related to nonseminoma via an effect on testosterone concentrations is unknown. Thus, an analysis of U.S. males was conducted, using data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) of the NCHS, CDC. Methods: Data from 2409 males aged &amp;gt;20 years were included in the analysis. Serum total testosterone (T) concentrations, determined using liquid chromatography-tandem mass spectrometry, were log transformed for statistical analyses. Marijuana use was categorized as: never, current (use on at least one day in prior 30 days) and past (no use within prior 30 days). Regular use was defined as use at least once a month for &amp;gt; 1 year. Covariates included age, body mass index, race/ethnicity, cigarette smoking status and time of day of phlebotomy. Adjusted mean T concentrations were compared among marijuana use categories using weighted multiple linear regression analysis accounting for the complex sample design of NHANES. In addition to the overall analysis, models were stratified by age (20-30 years, &amp;gt;30 years). Results: Mean T concentration did not differ between never- and ever-users of marijuana (p = 0.62), but did differ between never-users and regular-users (2.56 ng/mL vs 2.59 ng/mL, p = 0.03) and between never-users and current-users (2.60 ng/mL, p = 0.007). In the analysis restricted to men &amp;gt;30 years of age, significant differences in mean T concentration were evident among never-users and current-users (2.55 ng/mL vs 2.60 ng/mL, p = 0.003). Significant differences were also seen with increasing duration of use as mean T concentrations were higher among men who used marijuana regularly for &amp;gt;5 years. In the analysis of men 20-30 years of age, no significant differences in mean T concentration by marijuana use were seen. Conclusion: These results suggest that regular use and current use of marijuana are associated with higher T concentrations among U.S. men, particularly men &amp;gt; 30 years of age. As nonseminomas are more common in younger men than in older men, the results may indicate that the association between marijuana use and nonseminoma is not due to an effect of marijuana on circulating T concentrations. Citation Format: Katherine A. McGlynn. Marijuana use and serum testosterone concentrations among U.S. males. [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 1756.
Abstract 3572: AZ5576, a novel potent and selective CDK9 inhibitor, induces rapid cell death and achieves efficacy in multiple preclinical hematological models
Authors: Justin Cidado, Minhui Shen, Michael Grondine, Scott Boiko, Haiyun Wang, Alexandra Borodovsky, Anne Marie Mazzola, Alan Wu, Deborah Lawson, Douglas Ferguson, Beirong Gao, Andy Cui, Celina D’Cruz, Lisa Drew
Journal: Cancer Research (2016)

Abstract Cyclin-dependent kinase 9 (Cdk9) is a serine/threonine kinase that regulates elongation of transcription through phosphorylation of RNA polymerase II at serine 2 (pSer2-RNAPII). Mcl1, an anti-apoptotic protein that has been linked to increased survival and chemotherapy resistance in various cancers, can be indirectly modulated through transient inhibition of Cdk9 due to it having a short-lived transcript and being a labile protein. Transient inhibition of Cdk9, therefore, represents a potential therapeutic opportunity in tumors dependent on Mcl1 for survival, including various hematological malignancies. AZ5576 is a potent, highly selective, and orally bioavailable inhibitor of Cdk9 that inhibits Cdk9 enzyme activity with an IC50 &amp;lt;5nM and decreases phosphorlyation of Ser2-RNAPII in cells with an IC50 of 96nM. In the MLL-fusion containing acute myeloid leukemia (AML) line, MV411, short-term treatment with AZ5576 led to a rapid dose-dependent decrease in pSer2-RNAPII with concomitant loss of Mcl1 mRNA and protein, resulting in the cleavage and activation of caspase 3 and loss of cell viability. However, protein expression of other Bcl2 family members (e.g. Bcl2, BclxL, Bim) remained unchanged. Further, AZ5576 induced rapid caspase activation and loss of viability in a diverse set of hematological cancer cell lines, including those from acute myeloid leukemia (16/20), multiple myeloma (10/19), and diffuse large B-cell lymphoma (8/13). In vivo efficacy with intermittent dosing of AZ5576 was also demonstrated in multiple xenograft models from each hematological tumor type. Finally, AZ5576 was still able to induce loss of viability in various multiple myeloma lines cultured in the presence of cytokines or bone marrow stromal cells that represent potential protective effects of the tumor microenvironment. Together, these results highlight the therapeutic potential for selective CDK9 inhibition in the treatment of hematological malignancies. Citation Format: Justin Cidado, Minhui Shen, Michael Grondine, Scott Boiko, Haiyun Wang, Alexandra Borodovsky, Anne Marie Mazzola, Alan Wu, Deborah Lawson, Douglas Ferguson, Beirong Gao, Andy Cui, Celina D’Cruz, Lisa Drew. AZ5576, a novel potent and selective CDK9 inhibitor, induces rapid cell death and achieves efficacy in multiple preclinical hematological models. [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 3572.
Abstract 3066: Anti-angiogenic properties of PM060184
Authors: Carlos M. Galmarini, Maria J. Guillen, Juan F. Martinez-Leal, Marta Martinez-Diez, Pablo Aviles
Journal: Cancer Research (2016)

Abstract Vascular supply of tumors is one of the main targets for cancer therapy. Different studies have shown that most of the microtubule-binding agents present antiangiogenic and vascular-disrupting effects. PM060184 is a new marine-derived drug that binds to a new site in β-tubulin inhibiting tubulin polymerization. The compound is currently being evaluated in phase 1/2 studies in patients with advanced malignancies. The present study describes the antiangiogenic and vascular-disrupting properties of PM060184. Treatment of HUVEC endothelial cells with PM060184 resulted in depolymerization of the microtubule network. Differently from untreated cells, PM060184-treated cells showed a rounded morphology with a well-developed actin filament structure and plasma membrane blebs. Using transwell chambers pre-coated with matrigel™ or collagen matrix, we showed that PM060184 inhibited migration and invasion of HUVEC endothelial cells. We finally found that PM060184 interfered with the correct formation of the HUVEC capillary network grown on matrigel™; moreover, drug treatment also resulted in a significant disruption of the previously formed capillary-like network. This rapid collapse of the endothelial tubular network in vitro occurred in a concentration-dependent manner and was observed at concentrations lower than those affecting cells survival. These in vitro findings were confirmed in nude mice bearing MDA-MB-231 (breast) xenografts: after the administration of a single dose of PM060184 (at its MTD, 16 mg/kg,) a very strong reduction in the number of vessels was quantified in serial tumor sections stained with H&amp;E. Moreover, nude mice xenografted with H-460 (NSCLC) tumors and treated with a single dose of either 2 or 16 mg/kg of PM060184, experienced a strong and dose-dependent decrease of the intratumoral fluorescence after the administration of Angiosense™ 680, a fluorescence vascular imaging probe. Altogether, these data suggest that an anti-vascular mechanism is also contributing to the anti-tumor activities of PM060184. Citation Format: Carlos M. Galmarini, Maria J. Guillen, Juan F. Martinez-Leal, Marta Martinez-Diez, Pablo Aviles. Anti-angiogenic properties of PM060184. [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 3066.
Abstract 1643: p53 family and oncogenic signaling in cancer metastasis
Authors: Zhi-Xiong Xiao, Tao Lv, Yang Wan, Johann Bergholz, Yujun Zhang
Journal: Cancer Research (2016)

Abstract The tumor suppressor protein p53 is mutated in over 50% of human cancers. Multiple lines of evidence have shown that mutant p53 not only loses its ability to inhibit tumorigenesis, but also gains pro-metastatic functions. However, the molecular mechanisms underlying these effects are still not totally understood. In this study, we demonstrate that the p53 hotspot point mutant, p53(R273H), potently induces cell spreading, migration, and invasion. At the molecular level, p53(R273H) regulates the DLX2-NRP2 pathway in promoting cancer cell migration in vitro and metastasis in vivo. Interestingly, p53(R273H) strongly inhibits tumor cell growth in vitro and in xenograft nude mice model. In addition, we show that p53-related p63 inhibits Erk2 signaling in regulating cell migration/invasion. Citation Format: Zhi-Xiong Xiao, Tao Lv, Yang Wan, Johann Bergholz, Yujun Zhang. p53 family and oncogenic signaling in cancer metastasis. [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 1643.
Abstract 62: Functional analysis of endometrial cancer mutants of the E3 ubiquitin ligase adaptor protein, SPOP
Authors: Fred Lozy, Mary Ellen Urick, Meghan Rudd, Deena Maurer, Daphne W. Bell
Journal: Cancer Research (2016)

Abstract The purpose of this study is to functionally annotate endometrial cancer (EC) specific mutants of SPOP (Speckle-type POZ protein). SPOP is the substrate adaptor for the E3 ligase complex CUL3-SPOP-RBX1, which is responsible for mediating the ubiquitination, and subsequent proteasomal degradation of a number of protein substrates including the SRC3 (NCOA3/AIB1) oncoprotein. Our laboratory has previously shown that SPOP is frequently mutated in serous and clear cell ECs, two clinically aggressive subtypes of EC. Importantly, the vast majority of SPOP mutants localized within the MATH domain, which is responsible for substrate binding. We hypothesize that EC associated SPOP mutations encode loss-of-function mutants that abolish or attenuate substrate degradation. To test this hypothesis, we initially focused our attention on five SPOP mutations we uncovered in ECs (E47K, S80R, P94A, M117I and R121Q). HEK293 cells were transiently co-transfected with a HA-tagged SRC3-expressing construct and a MYC-tagged construct expressing either vector alone, wildtype SPOP, or mutant forms of SPOP. Protein lysates from transfected cells were subjected to Western blotting to measure exogenous levels of HA-SRC3 and MYC-SPOP. Cells exogenously expressing wildtype SPOP or the E47K, P94A, M117I or R121Q mutants exhibited lower levels of HA-SRC3 than cells expressing the vector control. In contrast, cells expressing the S80R mutant had elevated levels of HA-SRC3 compared to cells expressing either wildtype SPOP or the vector control. Co-immumoprecipitation experiments are being performed to assess the substrate binding capacity of SPOP mutants. Our findings indicate that the SPOP-S80R mutation, which is recurrent in EC, has an impaired ability to down-regulate SRC3 protein levels compared to wildtype SPOP. Ongoing and future studies aim to elucidate the mechanism that underlies the effect of SPOP-S80R, and to functionally annotate additional SPOP mutations in EC. Citation Format: Fred Lozy, Mary Ellen Urick, Meghan Rudd, Deena Maurer, Daphne W. Bell. Functional analysis of endometrial cancer mutants of the E3 ubiquitin ligase adaptor protein, SPOP. [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 62.
Abstract 4532: Deregulation of retinoic acid (RA) epigenetic control of sphingolipid signaling
Authors: Stefano Rossetti, Vincenzo Gagliostro, Nicoletta Sacchi
Journal: Cancer Research (2016)

Abstract All-trans retinoic acid (RA), the bioactive derivative of vitamin A, can paradoxically exert both anti-cancer and cancer-promoting actions. According to our studies, RA promotes breast cancer cell growth and invasion whenever it fails to exert its genome-wide epigenetic control of transcription via the RA receptor alpha (RARA). Factors that negatively affect RARA genomic function lead to genome-wide deregulation of the transcriptome epigenetically regulated by RA, including RARA-target genes controlling critical sphingolipid functions. We show here that functional inhibition of genomic RARA concomitantly leads to epigenetic repression of neutral sphingomyelinase 2 (nSMase2/SMDP3), a critical enzyme involved in the synthesis of pro-apoptotic ceramide, and upregulation of S1PR1, a key receptor of sphingosine-1-phosphate (S1P), a sphingolipid with pro-proliferative and pro-invasive activity. Selective activation of S1PR1 recapitulates RA pro-proliferative/pro-invasive action, while selective inhibition of S1PR1 counteracts it. Apparently, activation of the S1P-S1PR1 axis, combined with lack of RARA-mediated epigenetic control of SMPD3-ceramide axis, contributes to determine RA tumorigenic action. This study was supported by the NCI R01 CA127614 grant (NS). Citation Format: Stefano Rossetti, Vincenzo Gagliostro, Nicoletta Sacchi. Deregulation of retinoic acid (RA) epigenetic control of sphingolipid signaling. [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 4532.