tbuckley/cabot-search huggingface dataset:
Impact of risk-reducing oophorectomy on quality of life in women at risk for ovarian cancer
Authors: H. L. McArthur, M. Hensley, C. L. Brown, D. S. Chi, K. Offit, K. Hurley, Y. Li, M. L. Gemignani, M. E. Robson, R. R. Barakat
Journal: Journal of Clinical Oncology (2007)

1520 Background: Factors associated with quality of life (QOL) changes after risk-reducing salpingo-oopherectomy (RRSO) have not been clearly defined. We report the results of a prospective QOL study among women undergoing RRSO at the Memorial Sloan-Kettering Cancer Center. Methods: 101 women undergoing RRSO between April 2000 and April 2004 were included. Participants completed questionnaires evaluating perceived risk, symptoms, cancer-related worries/distress, sexual function and QOL at baseline, and at 6 and 12 months after RRSO. All questionnaires were adapted from validated, standardized instruments. Instrument score changes over time were evaluated by GLM repeated measures analysis. Results: The median age of the participants was 48y; 62.4% were post- menopausal; 47.5% had a deleterious BRCA mutation; 46.5% had a family history of OC; 73.3% had a personal history of breast cancer. 74.1% reported a perceived lifetime OC risk =25%. Mean total symptom and depression scores at baseline did not differ by menopausal status, BRCA mutation status, personal breast cancer history or OC family history. Menopausal subscale scores were significantly lower at baseline among pre-menopausal women. Baseline mean anxiety/distress scores and cancer-specific distress scores were significantly higher among mutation carriers than non-carriers. Among women who completed all 3 questionnaires (n=60), overall QOL measured by SF36 did not change over time. There was a significant interaction of menopausal status at surgery with the changes in total symptom and menopause subscale scores. There was a significant interaction between mutation status and post-operative decline in anxiety/distress scores. At 6 and 12 months, 24 (36.4%) and 22 (42.3%) of women, respectively, reported a worsened sex life and approximately 15% were dissatisfied with their decision to undergo RRSO. Conclusions: Most women perceived themselves at increased risk of OC and were satisfied with their decision to undergo RRSO. Mutation carriers demonstrated significant baseline OC-specific anxiety, but experienced a significant reduction post-RRSO. A significant increase in symptomatology was reported after RRSO, particularly among pre-menopausal women; however, there was no significant overall change in QOL. No significant financial relationships to disclose.
Metabolism, Covalent Binding, and Mutagenicity of Aflatoxin B&lt;sub&gt;1&lt;/sub&gt; by Liver Extracts From Rats of Various Ages&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Jayaraj, J P Hardwick, T W Diller, A G Richardson
Journal: JNCI Journal of the National Cancer Institute (1985)

The ability of S-9 fractions isolated from the livers of 4-, 12-, and 26-month-old male inbred F344 rats to activate and metabolize the hepatocarcinogen aflatoxin B1 [(AFB1) CAS: 1162-65-8] was studied. The following observations were made: 1) The activation of APB1 to compounds that are mutagenic in the Ames Salmonella-microsome test and to compounds that covalently bind DNA in vitro was similar for liver S-9 from 4- and 12-month-old rats. A 30–50% decrease in the activation of AFB1 occurred in rats between 12 and 26 months of age. 2) The in vitro metabolism of AFB1 to chloroform-soluble and water-soluble metabolites was similar for 4- and 12-month-old rats and decreased significantly in rats after 12 months of age. 3) The proportion of most of the chloroform-soluble metabolites of AFB1 formed by liver S-9 from 4-, 12-, and 26-month-old rats was similar. However, the proportion of aflatoxicol (CAS: 29611-03-8) produced by liver S-9 increased approximately twofold in rats between 12 and 26 months of age. 4) The cytochrome P450 content and the NADPH cytochrome c reductase activity of liver microsomes decreased 40–45% in rats between 12 and 26 months of age. However, the activities of UDPglucuronyltransferases and most forms of glutathione S-transferase did not change significantly with increasing age in liyer microsomes and cytosol, respectively.
Augmentation of Mouse Natural Killer Cell Activity by a Streptococcal Preparation, Ok-432&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: K Oshimi, S Kano, F Takaku, K Okumura
Journal: JNCI Journal of the National Cancer Institute (1980)

Streptococcal immunopotentiator OK-432 (NSC-B116209) augmented the natural killer (NK) cell activity of peritoneal exudate cells (PEC) in inbred C57BL/6 mice given ip injections of 0.1 mg OK-432 per mouse. The cytotoxic activity of PEC increased as early as 1 day after inoculation, reached its peak on day 3, and gradually declined thereafter, YAC-1, K562, and MOLT-4 target cells were more sensitive to PEC than were EL 4 and P815 target cells. The elimination of adherent cells by a nylon wool column enriched the proportion of cytotoxic cells among PEC. Nylon wool column-passed PEC were resistant to treatment with anti-Thy 1.2 antibody plus complement and sensitive to anti-asialo GM1 serum plus complement. Because 1:40-diluted rabbit antiserum against glycosphingolipid asialo GM1 is capable of eliminating mouse NK cell activity and is not cytotoxic to killer T-cells, the above results strongly suggest that OK-432 augments the NK cell activity in mice.
Effects of Tumor Promoters and Cocarcinogens on Growth and Differentiation of Cultured Human Esophageal Epithelial Cells
Authors: K Sasajima, J C Willey, S P Banks-Schlegel, C C Harris
Journal: JNCI Journal of the National Cancer Institute (1987)

The acute effects of 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 56937-68-9], T-2 toxin (CAS: 21259-20-1), capsaicin (CAS: 404-86-4), cigarette smoke condensate (CSC), and ethanol (CAS: 3807-77-0) were examined in secondary cultured human esophageal epithelial cells in serum-free LHC-8 medium. Effects were evaluated by morphology and measurement of clonal growth rate (population doublings per day), cross-linked envelope (CLE) formation, and the enzymatic activities of ornithine decarboxylase (ODC) and plasminogen activator (PA). All compounds tested were inhibitory to clonal growth; concentrations causing 50% growth inhibition were estimated as 10 nM TPA, 6 nM T-2 toxin, 40 microM capsaicin, 8 micrograms CSC/ml, 540 mM ethanol, and 0.8 microgram CSC/ml with 220 mM ethanol. None of the compounds tested induced CLE formation, although calcium ionophore (A23187) could induce CLE in at least 60% of the cells. TPA (10 and 100 nM) decreased the ODC activity of cells, and capsaicin (100 microM) induced ODC by 220%. TPA (1-100 nM) and capsaicin (100 microM) also induced PA activity. Slight increases in ODC activity by CSC (10 micrograms/ml), CSC (1 microgram/ml) with ethanol, and T-2 toxin (1 nM) were observed, but PA activity was not affected by these compounds. The results indicated that the response of human esophageal epithelial cells to TPA is both similar to and different from that reported for human epidermal and bronchial cells in vitro. Enhancement of PA activity and decrease in ODC by TPA are found in all three human epithelial cell types. However, these changes are not associated in esophageal cells with increased CLE formation as reported in studies with the use of bronchial and epidermal epithelial cells. The results from these acute studies provide the basis for designing in vitro carcinogenesis investigations using these agents.
THU0137 Denosumab, with and without Biologic Therapy and the Risk of Infection in Patients with Rheumatoid Arthritis
Authors: B. Haraoui, D. Choquette, A. Adjo'o Zo'o, L. Coupal
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The use of biologic agents (BA) in the treatment of rheumatoid arthritis have increased the risk of all types of infections, non-opportunistic as well as opportunistic. The introduction of denosumab, monoclonal antibody targeting the rank ligand, has been associated with a possible increased risk of infection during the pre-clinical phase. As denosumab has a different therapeutic objective, specifically prevention of bone loss, it may be used in conjunction with other biologic agents raising the risk of infections in patient with RA. <h3>Objectives</h3> To evaluate the risk of infection in patients with rheumatoid arthritis (RA) treated with denosumab alone or concomitantly with a biologic agent (BA). <h3>Methods</h3> Patients with RA followed at the Institut de Rhumatologie de Montréal and who were prescribed denosumab were followed prospectively between february 2005 and july 2014. Baseline demographics, co-morbidities, co-medication and infectious events were recorded in the RHUMADATA® database. Patients were divided in 2 groups, the first received denosumab concomitantly with a biologic agent (BA) and the second group took only denosumab without ever taking a biologic agent. The rate of infection was evaluated one year prior to the initiation of the denosumab and compared to the rate of infection during the exposure to denosumab in both groups. The data were analyzed using the SAS statistical software (Version 9.3). <h3>Results</h3> A total of 63 patients were ever prescribed denosumab, 20 concomitantly with a BA and 43 without a BA. Patients were on average 70.3 years of age, 92% were women, and had a mean (SD) RA disease duration of 18.6 (13.5) years. Exposure to denosumab was on average 1.9 years for Group 1 and 1.6 years for Group 2. No differences were noted for co-morbidities or co-medication between the 2 groups. For Group 1, the rates of infections per 100 pt.-years were respectively 35.0 in the year preceding the start of denosumab and 15.7 during the concomitant use with a BA (p=0.16). For Group 2 the rates were respectively 18.6 prior to denosumab use and 25.0 during denosumab use (p=0.49). <h3>Conclusions</h3> In this cohort of RA patients whose baseline characteristics were similar, the risk of any infection was not increased by denosumab given alone or in combination with a biologic agent. <h3>Disclosure of Interest</h3> None declared
The Hsp32/HO-1-targeted drug SMA-ZnPP counteracts the proliferation and viability of neoplastic cells in solid tumors and hematologic neoplasms
Authors: K. V. Gleixner, M. Mayerhofer, A. Vales, A. Gruze, W. F. Pickl, E. Lackner, C. Sillaber, C. C. Zielinski, H. Maeda, P. Valent
Journal: Journal of Clinical Oncology (2007)

14122 Background: Heat shock protein 32 (Hsp32) is a stress-related survival factor that is overexpressed in various neoplastic cells. Recently, specific Hsp32- targeting drugs such as styrene maleic acid encapsulated zinc protoporphyrin (SMA-ZnPP) have been developed. Methods: We examined the effects of SMA-ZnPP on proliferation and survival of various tumor cell-lines, including U97MG (glioblastoma), A549 (lung cancer), MDA-MB-231 (breast cancer), BxPC-3 (pancreatic), HepG2 (hepatocellular), Colo201, Colo320DM, DLD-1 (colon), OvCar3 (ovarian carcinoma), KG1, U937, HL60, K562 (myeloid leukemias), RAJI, NALM-6 (lymphatic leukemias), RPMI 8226, U266 (multiple myeloma) as well as on primary neoplastic cells. Moreover, Ba/F3 cells with doxycycline-inducible expression of oncoproteins (RAS-G12V, BCR/ABL, KIT-D816V) were analyzed. Expression of Hsp32 mRNA was examined by RT-PCR and Northern blotting, and expression of the Hsp32 protein by Western blotting. To silence Hsp32 in neoplastic cells, we used specific siRNA as well as SMA-ZnPP. Proliferation was analyzed by 3 H-thymidine uptake and apoptosis by light microscopy. Results: All neoplastic cells tested were found to express Hsp32 mRNA and the Hsp32 protein in a constitutive manner. In Ba/F3 cells, induction of RAS-G12V, BCR/ABL, or KIT D816V enhanced the expression of Hsp32. The Hsp32 siRNA was found to lead to a reduced viability and induction of apoptosis. Treatment of malignant cells with SMA-ZnPP resulted in a significant decrease in proliferation and induction of apoptosis. The effects of SMA- ZnPP on primary neoplastic cells and cell lines were dose-dependent and occurred at pharmacologic concentrations (IC 50 1–30 μM). Moreover, SMA-ZnPP was found to synergize with various anti-neoplastic drugs (cisplatin, cytarabine, tyrosine kinase inhibitors, bortezomib) in producing growth-inhibition in neoplastic cells. Conclusions: The Hsp32-targeting drug SMA-ZnPP counteracts malignant cell growth and sensitizes neoplastic cells against various other targeted or conventional antineoplastic drugs. Hsp32-targeting drugs may represent an interesting new aproach to inhibit malignant cell growth in solid tumors and leukemias. No significant financial relationships to disclose.
A meta-analysis of individual patient data from randomized trials assessing chemotherapy with and without estramustine in patients with castration-refractory prostate cancer
Authors: K. Fizazi, G. R. Hudes, W. R. Berry, W. K. Kelly, J. C. Eymard, C. Logothetis, A. Le Maitre, J. P. Pignon, S. Michiels
Journal: Journal of Clinical Oncology (2006)

4561 Background: Estramustine phosphate is a mustard-estradiol conjugate, with evidence of both hormonal and non-hormonal effects. In phase II trials, the response rates of microtubule inhibitors are increased when combined with estramustine. Morbidity includes notably thrombosis in about 7% of cases. Whether combining estramustine with chemotherapy increases survival in castration-refractory prostate cancer (CRPC) is still controversial. Methods: Data from all published and unpublished prospective randomized trials assessing chemotherapy + estramustine versus chemotherapy alone in CRPC were sought using electronic database searching, hand searching, and by contacting experts in the field. The primary endpoint was overall survival (OS). The analysis was performed on an intention-to-treat basis. The stratified logrank test was used and an overall hazard ratio (HR) was computed using a fixed effect model. χ 2 heterogeneity tests were used to test for statistical heterogeneity. All p-values were two-sided. Multivariate analysis was performed using a Cox model stratified by trial. Results: Individual data were obtained from all 5 randomized trials conducted in the PSA era that had been identified (n = 610). The control arms consisted of docetaxel (1), paclitaxel (1), ixabepilone (1), and vinblastine (2). With a median follow-up of 2.8 years, 510 deaths had occurred. OS was significantly better in the estramustine arm (HR = 0.82 [95% CI: 0.69–0.97]; p = 0.02). Overall, the risk reduction (RR) of death related to estramustine was 18% (± 8). There was no significant interaction (p = 0.66) between the RR of trials using vinblastine (RR = 15% [± 12]) and in those using taxanes or ixabepilone (RR = 21% [± 11]). The estimated 1-year OS rate was 57% and 50% in the estramustine arm and in the control arm, respectively. The 18-months OS rate was 43% and 35%, respectively. There was no interaction between the effect of estramustine and age, performance status, or serum PSA in the Cox model. Conclusions: Combining estramustine with chemotherapy increases OS over chemotherapy alone in patients with castration-refractory prostate cancer. [Table: see text]
Occupational HIV Transmission Among Male Adult Film Performers — Multiple States, 2014
Authors: Jason A. Wilken, Christopher Ried, Pristeen Rickett, Janet N. Arno, Yesenia Mendez, Robert J. Harrison, Dan Wohlfeiler, Heidi M. Bauer, M. Patricia Joyce, William M. Switzer, Walid Heneine, Anupama Shankar, Karen E. Mark
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 2014, the California Department of Public Health was notified by a local health department of a diagnosis of acute human immunodeficiency virus (HIV) infection* and rectal gonorrhea in a male adult film industry performer, aged 25 years (patient A). Patient A had a 6-day history of rash, fever, and sore throat suggestive of acute retroviral syndrome at the time of examination. He was informed of his positive HIV and gonorrhea test results 6 days after his examination. Patient A had a negative HIV-1 RNA qualitative nucleic acid amplification test (NAAT)(†) 10 days before symptom onset. This investigation found that during the 22 days between the negative NAAT and being informed of his positive HIV test results, two different production companies directed patient A to have condomless sex with a total of 12 male performers. Patient A also provided contact information for five male non-work-related sexual partners during the month before and after his symptom onset. Patient A had additional partners during this time period for which no locating information was provided. Neither patient A nor any of his interviewed sexual partners reported taking HIV preexposure prophylaxis (PrEP). Contact tracing and phylogenetic analysis of HIV sequences amplified from pretreatment plasma revealed that a non-work-related partner likely infected patient A, and that patient A likely subsequently infected both a coworker during the second film production and a non-work-related partner during the interval between his negative test and receipt of his positive HIV results. Adult film performers and production companies, medical providers, and all persons at risk for HIV should be aware that testing alone is not sufficient to prevent HIV transmission. Condom use provides additional protection from HIV and sexually transmitted infections (STIs). Performers and all persons at risk for HIV infection in their professional and personal lives should discuss the use of PrEP with their medical providers.
High-dose busulfan in patients with myeloma.
Authors: J Mansi, F da Costa, C Viner, I Judson, M Gore, D Cunningham
Journal: Journal of Clinical Oncology (1992)

PURPOSE To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance &lt; 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.
Tumors of the Urinary Bladder: An Analysis of the Occupations of 1,030 Patients in Leeds, England&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Honor M. Anthony, M.B., Ch.B., Gretta M. Thomas, M.D.
Journal: JNCI Journal of the National Cancer Institute (1970)

The whole-life occupational histories of 1,030 patients (812 men and 218 women) with papilloma and carcinoma of the bladder were analyzed. Bladder tumor patients whose smoking habits were known were matched with surgical control patients (340 men and 50 women) and with other cancer patients (312 men and 39 women) for sex, age decade, habitat, and smoking habits. Numbers in the matched pairs in different occupations (Registrar General's Classification of Occupations, 1966) were compared for predominant occupation, occupied at any time, and for 20 years or more. Results were confirmed from the distribution of occupations among the unmatched bladder tumor patients (429 men and 161 women) and from a comparison of expected and observed numbers in different occupations for the patients living in the City of Leeds (519 men and 146 women). The results confirmed the risk to dye workers and revealed risks to medical workers (mainly nurses), to tailors, tailors' pressers, and some groups of engineers and textile workers (associated with long-term employment only), and possibly also to hairdressers and tailors' cutters. Tumor occurred at younger ages in men who had been employed as dye workers, tailors' cutters (P = < 0.025), or hairdressers (not significant), but not in the other suspect occupations. Over 20% of bladder tumors in men in this series could be occupational in origin.
Preclinical antitumour activity and animal toxicology studies of rhizoxin, a novel tubulin-interacting agent
Authors: H R Hendriks, J Plowman, D P Berger, K D Paull, H H Fiebig, O Fodstad, H C Dreef-van der Meulen, R E Henrar, H M Pinedo, G Schwartsmann
Journal: Annals of Oncology (1992)
Activation of Pim Kinases Is Sufficient to Promote Resistance to MET Small-Molecule Inhibitors
Authors: Ningfei An, Ying Xiong, Amanda C. LaRue, Andrew S. Kraft, Bo Cen
Journal: Cancer Research (2015)

Abstract Mesenchymal-epithelial transition (MET) blockade offers a new targeted therapy particularly in those cancers with MET amplification. However, the efficacy and the duration of the response to MET inhibitors are limited by the emergence of drug resistance. Here, we report that resistance to small-molecule inhibitors of MET can arise from increased expression of the prosurvival Pim protein kinases. This resistance mechanism was documented in non–small cell lung cancer and gastric cancer cells with MET amplification. Inhibition of Pim kinases enhanced cell death triggered by short-term treatment with MET inhibitors. Pim kinases control the translation of antiapoptotic protein Bcl-2 at an internal ribosome entry site and this mechanism was identified as the basis for Pim-mediated resistance to MET inhibitors. Protein synthesis was increased in drug-resistant cells, secondary to a Pim-mediated increase in cap-independent translation. In cells rendered drug resistant by chronic treatment with MET inhibitors, genetic or pharmacologic inhibition of Pim kinases was sufficient to restore sensitivity in vitro and in vivo. Taken together, our results rationalize Pim inhibition as a strategy to augment responses and blunt acquired resistance to MET inhibitors in cancer. Cancer Res; 75(24); 5318–28. ©2015 AACR.