tbuckley/cabot-search huggingface dataset:
Randomized phase II study comparing 4 monthly doses of ipilimumab (MDX-010) as a single agent or in combination with a single dose of docetaxel in patients with hormone-refractory prostate cancer
Authors: E. Small, C. Higano, N. Tchekmedyian, O. Sartor, B. Stein, R. Young, J. Vestal, W. Moseley, S. Fischkoff, I. Lowy
Journal: Journal of Clinical Oncology (2006)

4609 Background: Ipilimumab is a fully human anti-CTLA-4 IgG1 monoclonal antibody that blocks CTLA-4 and augments immune responses. The current study evaluated the safety and activity of ipilimumab alone or with a single dose of docetaxel in hormone-refractory prostate cancer (HRPC). Methods: 43 chemotherapy naïve patients (pts) with HRPC, were treated; 23 were in arm A (ipilimumab at 3 mg/kg q 4 weeks × 4 doses) and 20 in arm B (ipilimumab as in Arm A and one dose of 75 mg/m 2 of docetaxel on day 1). Results: Six pts, 3 in each arm, demonstrated a decrease in PSA of &gt; 50%. Three pts, 2 in arm A, and 1 in arm B had confirmed PSA responses with durations of 79+ days, 169+ days, and 280 days, respectively. There were no radiologic responses with these PSA responses. Thirty-six (84%) of the 43 pts experienced 1 or more adverse events considered to be related to treatment with ipilimumab. The most common adverse events included fatigue (44%), pruritus (26%), nausea (19%), rash (12%), constipation (12%), and weight loss (12%). Serious adverse events (SAEs) occurred in 18 patients (42%), who experienced 52 SAEs. The majority (42 out of 52, 81%) were judged by the Investigator to be unrelated or unlikely to be related to treatment with ipilimumab. Five of the 52 SAEs reported in 3 pts were considered to be possible immune breakthrough events (IBEs), associated with drug exposure and consistent with an immune-based mechanism of action. These were adrenal insufficiency (1), diarrhea, colitis, and melena (all in one patient) and colitis (1). One of these pts had a confirmed PSA response. Conclusions: Ipilimumab was well tolerated in this group of pts with HRPC. Three pts overall (6%) experienced an IBE, a phenomenon that has been correlated in other studies with efficacy. There were several confirmed responses as assessed by PSA, one of which was correlated with an IBE. There was no apparent enhancement of activity by coadministration of a single dose of docetaxel. Further studies exploring ipilimumab in prostate cancer are warranted, either as monotherapy at higher doses, or in combination with immune modulators or vaccines. [Table: see text]
Combining Epigenetic and Immunotherapy to Combat Cancer
Authors: Katherine B. Chiappinelli, Cynthia A. Zahnow, Nita Ahuja, Stephen B. Baylin
Journal: Cancer Research (2016)

The most exciting recent advance for achieving durable management of advanced human cancers is immunotherapy, especially the concept of immune checkpoint blockade. However, with the exception of melanoma, most patients do not respond to immunotherapy alone. A growing body of work has shown that epigenetic drugs, specifically DNA methyltransferase inhibitors, can upregulate immune signaling in epithelial cancer cells through demethylation of endogenous retroviruses and cancer testis antigens. These demethylating agents may induce T-cell attraction and enhance immune checkpoint inhibitor efficacy in mouse models. Current clinical trials are testing this combination therapy as a potent new cancer management strategy. Cancer Res; 76(7); 1683-9. ©2016 AACR.
Central obesity in India is no longer confined to wealthier people, survey finds
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

More than a third of over 50s in India have a midriff bulge, and this is more common in women, the results of a nationally representative survey have shown.1

The findings also showed that obesity was not confined to India’s prosperous elite: although half (51%) of wealthier people had excess weight around their middle, over a quarter (28%) of people on low or middling incomes were also found to have central adiposity.

The …
Treatment of chemotherapy-induced breakthrough nauea and vomiting
Authors: R. M. Navari, S. E. Gray
Journal: Journal of Clinical Oncology (2009)

e20536 Background: Patients may experience breakthrough nausea and vomiting (BNV) despite adequate prophylaxis for chemotherapy-induced nausea and vomiting (CINV). BNV presents a difficult situation as treatment of ongoing nausea and vomiting is challenging. We investigated three different drug classes for the treatment of BNV: phenothiazines (prochlorperazine)(Pro), dopamine-serotonin receptor antagonists (metoclopramide) (Meto), and a corticosteroid-thiobenzodiazepine combination (dexamethasone plus atypical antipsychotic olanzapine) (Dex-Olan). Methods: Adult patients, receiving moderately emetogenic chemotherapy and CINV prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist and Dex pre-chemotherapy and Dex post-chemotherapy according to ASCO guidelines, who experienced BNV during the five days post-chemotherapy were randomized to receive Pro, 10 mg IV, and 10 mg, po, bid for three days; Meto, 20 mg IV, and 10 mg, po, bid for 3 days; or Dex, 20 mg IV and Olan, 5 mg, po, bid for three days. All patients also received at least one liter of IV fluids during the IV phase of their treatment. Patients were excluded if they had undergone rescue therapy with any of the study agents. Beginning with the first day of treatment for BNV (day 1) and daily through day 5, patients recorded episodes of vomiting/retching, nausea, other symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of any additional rescue therapy. One hundred six patients (median age 61, range 37 - 85, 60 males, ECOG performance status ≤ 2) consented to the protocol and 100 were evaluable. Results: A complete response (no emesis, no additional rescue) for the five days post-initiation of BNV treatment was recorded for 7 of 35 patients (20%) in the Pro regimen, 12 of 33 patients (36%) receiving the Meto regimen, and 21 of 32 patients (66%) receiving the Dex-Olan regimen. There were no Grade III or IV treatment related toxicities. Conclusion: The combination of Dex-Olan was an effective treatment for BNV and was significantly more effective than Pro or Meto alone. No significant financial relationships to disclose.
Crimes against discharged mental patients in board-and-care homes
Authors: A F Lehman, L S Linn
Journal: American Journal of Psychiatry (1984)

A survey of 278 persons discharged from mental hospitals who were living in board-and-care homes showed that one-third of them had been victims of crime during the preceding year. In a comparison of nonvictims, victims of theft, and victims of violence, it was found that victims of violence were younger, were more active socially, reported more psychopathology and less satisfaction with their lives, and engaged in more criminal behaviors themselves than the other groups. Both victim groups used emergency mental health services more than nonvictims did during the preceding year. Strategies for future research and interventions are discussed.
Photodynamic therapy with methyl aminolaevulinate 80 mg g<sup>−1</sup>for severe facial acne vulgaris: a randomized vehicle-controlled study
Authors: D.M. Pariser, L.F. Eichenfield, M. Bukhalo, G. Waterman, M. Jarratt
Journal: British Journal of Dermatology (2015)

Journal Article Photodynamic therapy with methyl aminolaevulinate 80 mg g−1 for severe facial acne vulgaris: a randomized vehicle‐controlled study Get access D.M. Pariser, D.M. Pariser Eastern Virginia Medical School Division of Dermatology, and Virginia Clinical Research Inc. 6161 Kempsville Circle Suite 200A Norfolk VA 23502 U.S.A Correspondence David M. Pariser. E‐mail: dpariser@pariserderm.com Search for other works by this author on: Oxford Academic Google Scholar L.F. Eichenfield, L.F. Eichenfield Rady Children's Hospital San Diego and University of California San Diego CA U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Bukhalo, M. Bukhalo Altman Dermatology Associates Arlington Heights IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar G. Waterman, G. Waterman Deaconess Clinic, Inc. Evansville IN U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Jarratt, M. Jarratt DermResearch, Inc. Austin TX U.S.A Search for other works by this author on: Oxford Academic Google Scholar on behalf of the PDT Study Group, on behalf of the PDT Study Group Search for other works by this author on: Oxford Academic Google Scholar A. Bhatia, A. Bhatia Search for other works by this author on: Oxford Academic Google Scholar D. Greenstein, D. Greenstein Search for other works by this author on: Oxford Academic Google Scholar F. Hamzavi, F. Hamzavi Search for other works by this author on: Oxford Academic Google Scholar J. Kantor, J. Kantor Search for other works by this author on: Oxford Academic Google Scholar ... Show more P.N. Speelman, P.N. Speelman Search for other works by this author on: Oxford Academic Google Scholar G.J. Murakawa, G.J. Murakawa Search for other works by this author on: Oxford Academic Google Scholar E. Tichy, E. Tichy Search for other works by this author on: Oxford Academic Google Scholar A. Zaengelin, A. Zaengelin Search for other works by this author on: Oxford Academic Google Scholar E. Frankel, E. Frankel Search for other works by this author on: Oxford Academic Google Scholar W. Werschler W. Werschler Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 4, 1 April 2016, Pages 770–777, https://doi.org/10.1111/bjd.14345 Published: 01 April 2016
Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)
Authors: Carlos Alfaro, Alvaro Teijeira, Carmen Oñate, Guiomar Pérez, Miguel F. Sanmamed, Maria Pilar Andueza, Diego Alignani, Sara Labiano, Arantza Azpilikueta, Alfonso Rodriguez-Paulete, Saray Garasa, Juan P. Fusco, Angela Aznar, Susana Inogés, Maria De Pizzol, Marcello Allegretti, Jose Medina-Echeverz, Pedro Berraondo, Jose L. Perez-Gracia, Ignacio Melero
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes. Experimental Design: MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) and advanced cancer patients (n = 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures. Results: IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset. Conclusions: IL8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control. Clin Cancer Res; 22(15); 3924–36. ©2016 AACR.
A Cooperative Assay of a Sample with Erythropoietic Stimulating Activity
Authors: GEOFFREY KEIGHLEY, PETER H. LOWY, HENRY BORSOOK, EUGENE GOLDWASSER, ALBERT S. GORDON, THEODORE C. PRENTICE, WALTER A. RAMBACH, FREDERICK STOHLMAN, DONALD C. VAN DYKE
Journal: Blood (1960)
Bryan Ross Kennedy
Authors: Iain Levack
Journal: BMJ (2016)

Bryan Ross Kennedy (“BRK”) from Fraserburgh Academy won a scholarship (bursary competition) to study medicine at the University of Aberdeen. He achieved distinctions in pharmacology and materia medica. After house jobs with Sydney Davidson and Tommy Morgan as chiefs, he embarked on a career in anaesthesia in Aberdeen. He passed the FFA when still a senior house officer and published clinical research in peer reviewed journals, which marked him …
Association Between Vaccine Refusal and Vaccine-Preventable Diseases in the United States
Authors: Varun K. Phadke, Robert A. Bednarczyk, Daniel A. Salmon, Saad B. Omer
Journal: JAMA (2016)

<h3>Importance</h3> Parents hesitant to vaccinate their children may delay routine immunizations or seek exemptions from state vaccine mandates. Recent outbreaks of vaccine-preventable diseases in the United States have drawn attention to this phenomenon. Improved understanding of the association between vaccine refusal and the epidemiology of these diseases is needed. <h3>Objective</h3> To review the published literature to evaluate the association between vaccine delay, refusal, or exemption and the epidemiology of measles and pertussis, 2 vaccine-preventable diseases with recent US outbreaks. <h3>Evidence Review</h3> Search of PubMed through November 30, 2015, for reports of US measles outbreaks that have occurred since measles was declared eliminated in the United States (after January 1, 2000), endemic and epidemic pertussis since the lowest point in US pertussis incidence (after January 1, 1977), and for studies that assessed disease risk in the context of vaccine delay or exemption. <h3>Findings</h3> We identified 18 published measles studies (9 annual summaries and 9 outbreak reports), which described 1416 measles cases (individual age range, 2 weeks-84 years; 178 cases younger than 12 months) and more than half (56.8%) had no history of measles vaccination. Of the 970 measles cases with detailed vaccination data, 574 cases were unvaccinated despite being vaccine eligible and 405 (70.6%) of these had nonmedical exemptions (eg, exemptions for religious or philosophical reasons, as opposed to medical contraindications; 41.8% of total). Among 32 reports of pertussis outbreaks, which included 10 609 individuals for whom vaccination status was reported (age range, 10 days-87 years), the 5 largest statewide epidemics had substantial proportions (range, 24%-45%) of unvaccinated or undervaccinated individuals. However, several pertussis outbreaks also occurred in highly vaccinated populations, indicating waning immunity. Nine reports (describing 12 outbreaks) provided detailed vaccination data on unimmunized cases; among 8 of these outbreaks from 59% through 93% of unvaccinated individuals were intentionally unvaccinated. <h3>Conclusions and Relevance</h3> A substantial proportion of the US measles cases in the era after elimination were intentionally unvaccinated. The phenomenon of vaccine refusal was associated with an increased risk for measles among people who refuse vaccines and among fully vaccinated individuals. Although pertussis resurgence has been attributed to waning immunity and other factors, vaccine refusal was still associated with an increased risk for pertussis in some populations.
Carcinogenicity of 5-Nitrofurans and Related Compounds With Amino-Heterocyclic Substituents&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: S Cohen, E Ertürk, A Von Esch, A Corvetti, G Bryan
Journal: JNCI Journal of the National Cancer Institute (1975)

Carcinogenicity of eight 5-nitrofurans with heterocyclic substituents at the 2-position of the furan ring was investigated by feeding the chemicals to SpragueDawley female rats. N-[5-(5-nitro-2-furyl)-1,3,4-thiadiazol-2- yl]acetamide induced in 30 rats the highest incidence of tumors with the greatest number of tissues involved: forestomach squamous cell tumors (22), kidney pelvis transitional cell carcinomas (lS), pulmonary alveolar cell carcinomas (16), hemangioendothelialsarcomas (20) of the intestine, mesentery, liver, lung, and pancreas, and a few tumors of other tissues. 2-Amino-5-(5-nitro-2-furyl)-1,3,4- thiadiazole, 2-amino-5-(5-nitro-2-furyl)-1,3,4-oxadiazole, and trans-2-[(dimethylamino)methylimino]-5-[2-(5-nitro- 2-furyl)vinyl]-1,3,4-oxadiazole produced high incidences of mammary tumors. The other four 5-nitrofurans tested: N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamidej 2,2,2trifluoro- N-[4-(5-n itro-2-furyl)-2-thiazolyl]acetamide; 5-(5nitro- 2-furyl)-1,3,4-oxadiazol-2-ol and N-{[3-(5-nitro-2furyl)- l ,2,4-oxadiazol-5-yljmethyl} acetamide were associated with tumor incidences of 40–60%. Two other chemicals were also tested: 2-Amino-5-nitrothiazole caused a low incidence of breast and kidney pelvis tumors, and 2-amino-4-(p-nitrophenyl)thiazole induced a high incidence of breast and salivary gland adenocarcinomas and Iymphomas.
Combination of paclitaxel and two schedules of gefitinib in patients with metastatic breast cancer
Authors: S. Cresta, A. Perotti, L. Merlini, M. Mansutti, A. Marchianã, G. Grasselli, G. Bianchini, C. Ferrario, G. Capri, L. Gianni
Journal: Journal of Clinical Oncology (2006)

10599 Background: The epidermal growth factor receptor (EGFR) may be overexpressed in breast cancer. Inhibition of EGFR signaling by gefitinib (Iressa) enhances the in vitro antitumor activity of many cytotoxic drugs including paclitaxel. Methods: In this phase II study patients (pts) with measurable metastatic breast cancer and maximum prior exposure to two chemotherapies were randomized to paclitaxel (100 mg/m 2 on days 1, 8 q21) and continuous gefitinib, 250 mg daily for 21 days (arm A); or paclitaxel (100 mg/m 2 on days 8, 15 q21) with gefitinib 250 mg daily from day 1 to 15 (arm B). Therapy continued for at least 4 cycles after best response. After 6 cycles, responding pts continued with gefitinib monotherapy until progression or unacceptable toxicity. Results: 16 pts in arm A and 17 in arm B were enrolled; 25 had visceral disease (12 in arm A and 13 in arm B). Median age was 53 years (range 29–70). All but one pt received prior anthracyclines and 9 also prior taxanes. Overall 17 pts responded to therapy (intent to treat analysis; arm A: 62.5%, 95% CI: 35.4–84.8%; arm B: 41.2%, 95% CI: 18.4–67.1%). Disease control (CR+PR+SD) was achieved in 81.3% of pts in arm A and 76.5% in arm B, with 10 and 6 pts who continued with gefitinib monotherapy after completing the combination schedule. Median time to progression was 250 (arm A) and 204 days (arm B), while median response duration was 212 (arm A) and 285 days (arm B). Tolerability was good with either schedule of gefitinib. Diarrhea was frequent (68.8% and 64.7%) and of grade 3–4 severity in 6% of pts in arm A and in arm B. Grade 3–4 neutropenia affected 6% and 12% of pts respectively, and 6% of pts in both arms had a grade 3–4 increase of AST and ALT. Other grade 1–2 adverse events included acneiform rash (100% in arm A and 58.8% in arm B), sensory neuropathy (68.8% and 58.8%), anemia (50.0% and 52.9%), neutropenia (25.0% and 17.6%) and myalgia (37.5% and 41.2%). Conclusions: The combination of paclitaxel with gefitinib given continuously or for 2 out of every 3 weeks is feasible and well tolerated. The discontinuous schedule caused less skin toxicity. The good antitumor activity deserves further studies to identify sensitive subgroups and mechanisms of sensitivity. IRESSA is a trademark of the AstraZeneca group of companies. [Table: see text]
Effect of gender and age on overall survival in patients with esophageal cancer
Authors: R. S. Chhibar, D. Yang, W. Zhang, G. Lurje, A. Pohl, Y. Ning, A. El-Khoueiry, S. Iqbal, H. J. Lenz
Journal: Journal of Clinical Oncology (2009)

4541 Background: The American Cancer Society estimated that during 2008 approximately 16,470 new esophageal cancer cases would be diagnosed in the United States. Previous studies indicate that the incidence of esophageal cancer is more in males than females; however the influence of sex in the progression of esophageal cancer is not clearly understood. In vitro and in vivo models showed that administration of estradiol significantly inhibited the growth of ER-positive and AR-positive KSE-1 tumors in both males and females in conjunction with an increase in the estradiol levels and a decrease in the DHT levels in the serum. Thus we tested the clinical significance of sex in the overall survival of esophageal cancer using SEER data. Methods: A total of 21,584 patients with localized and metastatic esophageal cancer from 1988–2004 were screened using the SEER registry. The patients were divided into age at diagnosis, sex and ethnicity. The analysis for overall survival was based on the Cox proportional hazards model adjusted for marital status, site of primary tumor, treatment, histology and tumor grade and stratified by year of diagnosis and SEER registry site. Pairwise interactions (age and sex, age and race, and sex and race) were also examined. Results: Females with localized esophageal cancer had significantly longer overall survival compared to males (p&lt;0.001). In metastatic esophageal cancer, females seemed to have longer overall survival than males (p=0.054). Overall survival decreased with increasing age (p&lt;0.001). African Americans with localized esophageal cancer have worse median overall survival compared to Caucasians (p&lt;0.001). No significant difference was noted with respect to ethnicity in metastatic esophageal cancer (p=0.22). Also pairwise interactions did not have significant difference. Conclusions: This is the first and largest study showing gender as an independent prognostic factor in patients with localized and metastatic esophageal cancer. Females had a significant better overall survival than males in esophageal cancer suggesting that sex hormone pathways may have a potential impact on tumor progression. These data warrant further studies to explore the role of these pathways in the diagnosis and treatment of esophageal cancer. No significant financial relationships to disclose.