tbuckley/cabot-search huggingface dataset:
Abstract 5407: T-type Ca2+ channel inhibitors sensitize ovarian cancer to carboplatin through downregulation of survivin gene expression
Authors: Barbara Dziegielewska, Eli V. Casarez, Wesley Z. Yang, Jaroslaw Dziegielewski, Jill K. Slack-Davis
Journal: Cancer Research (2015)

Abstract Recent studies by our group and others have shown that T-type Ca2+ channels play a reinforcing role in cancer cell proliferation, cell cycle progression and apoptosis evasion. We have demonstrated drug cooperativity between T-type Ca2+ channel inhibitor, mibefradil and carboplatin in vivo in ovarian cancer xenografts. To investigate the molecular mechanism by which T-type Ca2+ channels affect tumor growth, we used a panel of ovarian cancer cell lines together with mibefradil or small interfering RNA (siRNA) to silence the T-channels gene expression. Inhibition of T-type Ca2+ channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer with simultaneous increase in apoptosis and decrease in expression of the anti-apoptotic gene survivin (BIRC5). Combining carboplatin with mibefradil resulted in increased apoptosis. Analysis of intracellular signaling revealed T-type Ca2+ channel inhibitors induced changes in the levels of FOXO proteins, which regulate BIRC5 gene expression. Mibefradil treatment caused greater nuclear retention of FoxO1 and FoxO3a, two transcription factors that repress BIRC5 expression, while protein expression of the transcription factor that activates BIRC5 expression, FoxM1, decreased. Chromatin immunoprecipitation of FOXO proteins from mibefradil treated ovarian cancer cells demonstrated binding of FoxM1 and FoxO1 within the BIRC5 (survivin) promoter. Together, the data show that T-type Ca2+ channels support ovarian cancer cell cycle, proliferation and regulate pro-survival pathways through the FOXO-survivin signaling axis, which has been reported to be deregulated in ovarian cancer. Moreover, our results provide the rationale for future use of T-type antagonists as sensitizing agents in combination with standard chemotherapeutics. Citation Format: Barbara Dziegielewska, Eli V. Casarez, Wesley Z. Yang, Jaroslaw Dziegielewski, Jill K. Slack-Davis. T-type Ca2+ channel inhibitors sensitize ovarian cancer to carboplatin through downregulation of survivin gene expression. [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 5407. doi:10.1158/1538-7445.AM2015-5407
Dehydroepiandrosterone in metastatic castration-resistant prostate cancer: Preliminary results from the SU2C-PCF West Coast Dream Team (WCDT).
Authors: Won Kim, Charles J. Ryan, Li Zhang, Jack Youngren, John Wilton, Joshi J. Alumkal, Tomasz M. Beer, Robert Baertsch, Josh Stuart, Kim N. Chi, Martin Gleave, Matthew Rettig, Robert Evan Reiter, Primo Lara, Christopher P. Evans, Eric Jay Small
Journal: Journal of Clinical Oncology (2016)

179 Background: Aberrant androgen receptor (AR) phenotypes (e.g. splice variants, amplification) are strongly correlated with abiraterone (Abi) and enzalutamide (Enz) resistance. Low serum dehydroepiandrosterone (DHEA) is also associated with poor outcomes to AR-targeted therapy. Here, we investigate the relationship between serum DHEA, AR phenotype, and treatment efficacy in the WCDT. Methods: Patients (pts) with progressive mCRPC enrolled to the WCDT from UCSF, OHSU, UCLA, UBC, and UCD were included in this analysis. Serum DHEA was analyzed via high-pressure liquid chromatography and tandem mass spectrometry. Limit of quantitation (LQ) of DHEA was 0.2ng/mL. Full-length AR (AR-FL) and AR-v7 expression, obtained via RNAseq of metastatic tumor biopsies, was expressed as total reads mapped to gene. PSA response (PSAr) was defined as ≥ 50% PSA decline. Results: 35 pts were included in this analysis: 15 had treatment-naïve mCRPC, and 20 had prior AR-targeted therapy (14 Abi, 6 Enz). All pts were docetaxel-naïve. 11 pts had DHEA &lt; LQ; of these, 10 had received prior AR-targeted therapy. 12 pts received subsequent chemotherapy, and 23 received subsequent Abi/Enz (7 Abi, 16 Enz). In pts with DHEA &lt; LQ, 4/5 (80%) chemotherapy-treated pts had PSAr, while 1/6 (17%) Abi/Enz-treated pts had PSAr. In pts with DHEA ≥ LQ, 2/7 (27%) chemotherapy-treated pts had PSAr, while 9/16 (56%) Abi/Enz-treated pts had PSAr. The relationship between DHEA and PSAr was significantly different between the treatment groups (p = 0.0285). DHEA was higher in patients with PSAr to Abi/Enz versus those without PSAr (median, 0.871 versus 0.275ng/mL, p = 0.006). In an analysis of 27 pts with RNAseq data, the AR-v7/AR-FL ratio was significantly higher in those with DHEA &lt; LQ (median ratio 8.91, versus 3.38 in DHEA ≥ LQ, p = 0.032). Conclusions: In this exploratory analysis, there is a significant difference in the relationship between DHEA and PSAr in chemotherapy- versus Abi/Enz-treated patients. DHEA &lt; LQ was also associated with a higher AR-v7/AR-FL ratio, a potential avenue for further exploration of tumor biology. These results support a larger study to evaluate DHEA as a potential biomarker in mCRPC. Clinical trial information: NCT02432001.
Nosocomial outbreak of scabies in a hospital in Spain
Authors: A. Larrosa, M Cortés-Blanco, S. Martinez, C Clerencia, L  J Urdaniz, J Urban, J Garcia
Journal: Eurosurveillance (2003)

An outbreak of scabies occurred in a ward of a local hospital in Barbastro (Huesca, Spain), between November 2002 and January 2003. The outbreak was linked to a patient infested with mites when he was admitted to the ward on 1 November 2002. The first case had onset of symptoms on 5 November and the last one on 5 January 2003. Seventeen cases were reported: 11 healthcare workers (HCWs) and six patients.The outbreak was attributed to a delay in diagnosis, and lack of individual protection measures by caregivers. The use of short-sleeved coats is an habitual risk practice in this ward. Contact with fomites, animals, infested clothes or intimate contact with people other than their usual partners were dismissed as risk factors for the infestation. The different groups of caregivers in this ward presented a similar risk of becoming infested, and the mechanism of transmission was probably person to person contact. The implementation of specific guidelines for scabies prevention and treatment, as well as an active surveillance system, were fundamental to the control of this outbreak.
Germ cell tumors: there is still plenty to learn.
Authors: G J Bosl
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.1998.16.4.1244 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9552021 Germ cell tumors: there is still plenty to learn. G J BoslxG J BoslSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.4.1244 First Page PDF © 1998 by American Society of Clinical Oncology
Website of the week: Risk of cardiovascular disease
Authors: Douglas Carnall
Journal: BMJ (2000)

This week the BMJ revisits the issue of coronary risk, publishing no fewer than three instruments designed to support doctors' decision making in situations of cardiovascular risk. The consensus is that absolute risk, rather than any one risk factor, is what needs to be managed. Underpinning it all is the longitudinal data from the Framingham study. Its authors have produced similar charts to those published in this week's BMJ, and you can download them as lightweight (10 kb) PDFs at www.nhlbi.nih.gov/about/framingham/riskabs.htm.
Mechanical ventilation in ARDS
Authors: E. Roupie, M. Dambrosio, H. Mentec, A. Carneiro, F. Lemaire, L. Brochard, M. R. P. Amato, C. S. V. Barbas, D. M. Medelros, C. A. Lin, C. R. R. Carvalho, K. Lewandowski, K. J. Falke, R. Rossaint, K. Slama, D. Pappert, B. Kuhlen, F. Lopez, T. Grüning, K. Falke, Jm Dubois, Ph Gaussorgues, M. Sirodot, Jm Sab, G. Chatte, B. Langevin, D. Robert, R. Boiteau, T. Lherm, H. Hmouda, A. Tenaillon, E. Valente, N. Bloch, M. Rousset
Journal: Intensive Care Medicine (1992)
Impact of complete molecular response on survival in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Nicholas J. Short, Elias Jabbour, Koji Sasaki, Keyur Patel, Susan M. O’Brien, Jorge E. Cortes, Rebecca Garris, Ghayas C. Issa, Guillermo Garcia-Manero, Rajyalakshmi Luthra, Deborah Thomas, Hagop Kantarjian, Farhad Ravandi
Journal: Blood (2016)
Sequentially Alternating Hormone Chemotherapy with High-Dose Medroxy-Progesterone Acetate and Low-Dose Epirubicin for the Treatment of Hormone-Resistant Metastatic Prostatic Cancer
Authors: M Kontturi, M Sotarauta, T Tammela, O Lukkarinen, M L Romppainen, P Gröhn
Journal: European Urology (1988)
Abstract B44: Acquisition of meiotic DNA repair regulators maintain genome stability in glioblastoma
Authors: Maricruz Rivera, Qiulian Wu, Petra Hamerlik, Anita Hjelmeland, Shideng Bao, Jeremy Rich
Journal: Cancer Research (2015)

Abstract Glioblastoma (GBM), the most prevalent type of primary intrinsic brain cancer in adults, remains universally fatal despite maximal therapy, including radiotherapy and chemotherapy. Cytotoxic therapy generates double stranded DNA breaks (DSBs), most commonly repaired by homologous recombination (HR). We hypothesized that cancer cells coopt meiotic repair machinery as DSBs are generated during meiosis and repaired by molecular complexes distinct from genotoxic responses in somatic tissues. Indeed, we found that gliomas express meiotic repair genes and their expression informed poor prognosis. We interrogated the function of Disrupted Meiotic cDNA1 (DMC1), a homolog of RADiation sensitive51 (RAD51), the primary recombinase used in mitotic cells to search and recombine with the homologous DNA template. DMC1, whose only known function is as an HR recombinase, was expressed by GBM cells and induced by radiation. While targeting DMC1 in non-neoplastic cells minimally altered cell growth, DMC1 depletion in GBM cells decreased proliferation, induced activation of Checkpoint kinase 1 (CHK1) and expression of p21CIP1/WAF1, and increased replication protein A (RPA) foci, suggesting increased replication stress. Combining loss of DMC1 with ionizing radiation (IR) inhibited activation of DNA damage responses and increased radiosensitivity. Furthermore, loss of DMC1 reduced tumor growth and prolonged survival in vivo. Our results suggest that cancers coopt meiotic genes to augment survival under genotoxic stress, offering molecular targets with high therapeutic indices. Citation Format: Maricruz Rivera, Qiulian Wu, Petra Hamerlik, Anita Hjelmeland, Shideng Bao, Jeremy Rich. Acquisition of meiotic DNA repair regulators maintain genome stability in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B44.
Nutrition and Infection.
Authors: R Rakotoarimanana
Journal: Annals of Internal Medicine (1966)

Undernutrition leads to a global immune deficiency. What is the influence of undernutrition on the occurence and development of an infectious disease? How does an infection act on nutritional state of a patient? Is it possible to improve nutritional state by treating an infection and inversely, is it possible to prevent the arrival of an infectious disease by improving nutritional state? This article summarizes answers to these questions and takes up the subject of infectious complications related to nutritional treatment and parenteral nutrition in particular. Some exemples of pharmaconutrition are also mentioned.
Ancient Retrovirus Targeted by Engineered T Cells in Melanoma—Letter
Authors: John M. Grange, Bernd Krone
Journal: Clinical Cancer Research (2015)

Krishnamurthy and colleagues have described the production, by genetic engineering, of cytotoxic T cells that specifically recognize and lyse melanoma cells expressing a retroviral envelope protein HERV-K-ENV, thereby providing a potential novel therapeutic strategy (1). In this context, studies conducted by the Febrile Infections and Melanoma (FEBIM) group of the European Organization for Research and Treatment of Cancer have shown that vaccination with Bacille Calmette–Guérin (BCG) and/or vaccinia early in life afforded a significant level of protection against the development of melanoma later in life (2). It was also found that the prognosis of patients with melanoma was significantly enhanced in those who had previously received one or both of these vaccines (3). A postulated mechanism for this protection is the presence of epitopes homologous to the “satellite” peptide HERV-K-MEL in these vaccines, thereby facilitating the generation of cross-reacting immune responses (4).It was also shown that protection is afforded by certain serious but increasingly uncommon infectious diseases caused by pathogens likewise expressing HERV-K-MEL homologs (2), suggesting a role for infections in driving the evolution of immune surveillance mechanisms. It also suggests an association between the increase in the prevalence of melanoma in several industrially developed countries and the decreasing incidence of the relevant infectious diseases, cessation of vaccinia vaccination, and the diminishing use of BCG vaccination.Accordingly, there is evidence that the expression of “ancient” retroviruses on tumors can be harnessed for therapeutic intervention but also, by use of available vaccines, namely, BCG and possibly yellow fever 17D vaccine (5), to induce a useful level of long-lasting cross-reactive immune protection against melanoma and, perhaps, other cancers, including certain breast tumors that are known to express HERV-encoded epitopes.B. Krone is listed as a co-inventor on a patent on immune prevention of melanoma that is owned by the University Goettingen, Germany. No potential conflicts of interest were disclosed by the other author.
Abstract P4-09-27: ABC transporter expression: Clues into chemoresistance of triple negative breast cancers
Authors: R Feldman, B Abbott, S Reddy, Z Gatalica, M Castro
Journal: Cancer Research (2016)

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive histological subtype with high rates of recurrence and metastatic disease. Intrinsic or acquired multidrug resistance facilitated by the over-expression of drug efflux pumps (ABC transporters: BCRP [ABCG2], MRP1 [ABCC1] and PGP [ABCB1]), may contribute to the aggressive nature of this disease. We examined the expression patterns of drug efflux pumps for insight on their potential role in chemoresistance of TNBC. Methods: 1393 TNBC patients molecularly profiled with a commercial assay (Caris Life Sciences) were evaluated retrospectively for expression of BCRP, MRP1 and PGP by immunohistochemistry. Antibodies used: PGP (C494), BCRP (6D171) and MRP1 (33A6). IHC threshold: positive = ≥1+ and ≥10%). This data set also included metachronous paired samples from 71 TNBC patients. JMP was used to ascertain distributional differences. Results: PGP and MRP1 positive expression rates were 8.4% (117/1393) compared to 78.2% (248/317), respectively, displaying an inverse association (p=0.0001). BCRP was over-expressed in 52% (90/173). Co-expression data for all three transporters was available for 153 patients. BCRP/MRP1 co-expression was most abundant, 39% (59/153), followed by MRP1/PGP at 4% (6/153) and BCRP/PGP at 2% (3/153). Furthermore, 12% (18/153) of TNBC exhibited positive expression for all three drug pumps (16/18 or 89% were from patients with metastatic disease) and 14% (22/153) exhibited negative expression for all three drug pumps (15/22 or 68% were from patients with metastatic disease). Interestingly, positive MRP1 status, but not BCRP or PGP, correlated with metastatic disease (p=0.0061). In the paired data analysis, PGP expression was absent in 77% (55/71) and retained lack of expression in subsequently profiled specimens, 3% (2/71) retained positive PGP status, 13% (9/71) lost expression of PGP and 7% (5/71) gained expression of PGP. 36/40 patients that lacked PGP expression and 8/9 patients that "lost" PGP expression, exhibited and retained expression of MRP1 in the initial and subsequently-profiled specimens. Conclusion: Biomarker expression patterns of drug efflux pumps may provide insight to the chemoresistance phenotype observed in TNBC. Expression of MRP1 is favored in TNBC and is correlated with metastatic disease status. Although PGP expression may be absent or lost during TNBC progression, MRP1 (and BCRP) expression are almost always retained. Utilization of chemotherapies that are substrates of PGP, but not MRP1, (based on expression status) may be worthy of future investigation. Citation Format: Feldman R, Abbott B, Reddy S, Gatalica Z, Castro M. ABC transporter expression: Clues into chemoresistance of triple negative breast cancers. [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 P4-09-27.
Croonian Lectures on Functional Derangements of the Liver
Authors: C. Murchison
Journal: BMJ (1874)

6. Vertigo; 7. Contvulsions; 8. Noises in Ears; 9. Sleeplessness ; Io.Depression of Spirits; II.Irritability; 12. Thze 71tp oaidl Stalte.T'itr facts an(d argtuients wvhich I have now brought under your notice hiave led me to the conicluision that functional derangement of the liver, by ilnterfering wx ith the normal disintegration of albuminous matter, and by tlle productioni of peccaist substances which are not readily eliimin- atedl, and w-hiclh, thcrcfore, accumulate in the system, may, in the long r-uni, lead to maoiy of the most serious maladies-both acute anti chronic- to wx hich our race is subject.I shall now proceed to consi(ler certain sylptoms, inldicatinng (lerangement of the different physiological systems, but not constituLting distinct diseases, which appear to result from func- tional disorder of the liver.-Deran gemezts of the Ogants oj Dizgestion.i. Thc Tongtue.-It is ell to remember that there may be consider- able functional deran gement of the liver, and yet the tongue may be perfectly clean an(d nolormal, or at most onily slightly coated in the morning- hut in many caSes, anid particularly if the derangement be of old stand- ing, the tongue preselnts the appearances commonly described as charac- teristic of "atonic dlyspepsia".It is large, pale, and flabby, and in- diented by the teeth at the edge of the anterior third, while its stirface is lwhite, and the papilire are often elongated, so as to produce a pilous ap- pearance.If the liver be somewvhat congested, with these appearances we may often observe the fungiform papilloe on the tip and edges larger and redder than natural.
Selective decontamination of the digestive tract
Authors: A Liberati
Journal: BMJ (1994)

fingers was captured by a sculpture (fig 1).A useless armamentarium of crude instruments was presented in theatre (fig 2).Her fingers were freed when my variable speed Hobbydrill was used with its cutting attachment; the blade of tissue forceps was interposed to protect the tissues.This equip- ment helped save the child's fingers.She was allowed home the next day, and there was no sign of the injury at follow up six weeks later.
A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells
Authors: Andreas Reinisch, Daniel Thomas, M Ryan Corces, Xiaohua Zhang, Dita Gratzinger, Wan-Jen Hong, Katharina Schallmoser, Dirk Strunk, Ravindra Majeti
Journal: Nature Medicine (2016)
Activity of eribulin mesylate (E7389) in patients with soft tissue sarcoma (STS): Phase II studies of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC 62052).
Authors: P. Schoffski, I. L. Ray-Coquard, A. Cioffi, N. Bin Bui, S. Bauer, J. T. Hartmann, R. Sciot, J. Wanders, D. Druyts, P. Hohenberger
Journal: Journal of Clinical Oncology (2010)

10031 Background: Eribulin is a synthetic analogue of halichondrin B derived from marine sponges. It inhibits microtubule dynamics via a novel mechanism that is distinct from that of other tubulin-targeting agents, and induces cell cycle arrest and tumor regression in preclinical models. EORTC 62052 assessed the efficacy and safety of eribulin mesylate in 4 independent strata of pts with STS: leiomyo- (LMS,39 pts), adipocytic (ADI,38), synovial (SYN,19) and other (OTH,32) sarcomas. Methods: Pts with intermediate or high grade STS who had received no more than 2 lines of previous chemotherapy (up to 2 single agents or 1 combination) for advanced disease, with documented progression, good performance status and organ function were eligible. Eribulin 1.4 mg/m2 was given i.v. over 2-5 min days 1 and 8 q3w until intolerance or progression. The primary end point was the progression-free rate at 12 wks (PFR12wks) according to RECIST. Secondary end points included safety, response and survival. A Simon 2-stage design was applied (P1: 40%; P0: 20%; α=β=0.1) per stratum. Histopathology and responses were reviewed. Results: Grade 3-4 drug-related AEs occurring in >1 pat were leucopenia (33% of pts), neutropenia (50%), anemia (9%), fatigue (4%), febrile neutropenia, increases in ALAT, and infection without neutropenia (3% each). The PFR12wks was 32% (12/37 evaluable pts) in LMS, 45% (15/33) in ADI, 21% (4/19) in SYN and 19% (5/26) in OTH. The median PFS in LMS was 3 mo (95% confidence interval [CI] 2-5), the median OS 20 (CI 14-N) mo, with 70% of pts alive at 1 year. The PFS in ADI was 3 (CI 2-6) mo, the OS 10 (CI 8-16) mo, with 48% alive at 1 year. The PFS in SYN was 3 (CI 2-3) mo, the OS 11 (CI 7-15) mo, with 36% alive at 1 year. The PFS in OTH was 2 (CI 1- 3) mo, the OS 6 (CI 5-15) mo, with 30% alive at 1 year. Responses included CR, PR and stable disease. Conclusions: Eribulin mesylate is well tolerated in pretreated pts with STS. It deserves further study in well-defined subtypes of sarcoma, as the PFR12wks reached predefined statistical boundaries by the Simon 2-stage design in LMS and ADI. Responses and patient benefit were observed in various histotypes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai AAIrm, Novartis
467P Efficacy of cranial radiotherapy prior to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer patients with brain metastases
Authors: N. Tsushita, Y. Goto, H. Shiraishi, K. Tsuruoka, K. Yoshida, K. Itahashi, T. Asao, S. Kitahara, S. Kanda, H. Horinouchi, Y. Fujiwara, H. Nokihara, N. Yamamoto, Y. Ohe
Journal: Annals of Oncology (2015)