tbuckley/cabot-search huggingface dataset:
Phase II Study of Oral Platinum Drug JM216 as First-Line Treatment in Patients With Small-Cell Lung Cancer
Authors: E. Fokkema, H. J.M. Groen, J. Bauer, D. R.A. Uges, C. Weil, I. E. Smith
Journal: Journal of Clinical Oncology (1999)

This multicenter phase II trial was performed to determine tumor efficacy and tolerance of the oral platinum drug JM216 in patients with small-cell lung cancer (SCLC).Patients with SCLC limited disease unfit for intensive chemotherapy or those with extensive disease received JM216 120 mg/m(2)/d for 5 consecutive days every 3 weeks. Individual dose escalation to 140 mg/m(2)/d was allowed if toxicity was </= grade 2 according to the National Cancer Institute Common Toxicity Criteria. Tumor response was evaluated according to World Health Organization criteria.Twenty-seven patients were assessable for toxicity and 26 for tumor response. Eighty-eight cycles were administered. Common Toxicity Criteria grade 3 and 4 hematologic toxicities were neutropenia in 15.9% and 3.7%, lymphocytopenia in 47.6% and 17.1%, and thrombocytopenia in 19.5% and 10.3% of cycles, respectively. One patient suffered from neutropenic fever. Nausea, vomiting, and diarrhea were the most common nonhematologic toxicities. Except for grade 4 diarrhea in one patient, no grade 4 nonhematologic toxicity was observed. No severe neurotoxicity or nephrotoxicity was observed. Tumor response rate was 10 of 26 (38%; 95% confidence interval, 19% to 58%), excluding five unconfirmed partial responses. No complete responses were observed. Median overall time to progression was 110 days (range, 5 to 624 days). Median overall survival time was 210 days (range, 5 to 624 days).Oral JM216 is active in previously untreated patients with SCLC and shows mild toxicities.
Depression in teenagers can be identified with three questions, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Asking three simple questions can accurately detect depression in adolescents aged 14 to 16, a Scandinavian primary care study has shown,1 demonstrating that the questions had comparable sensitivity to a current “gold standard” written questionnaire for diagnosing depression.

Depression can have serious consequences for the health and lives of teenagers, but validated tools for GPs to diagnose depression in this age group are currently limited.

Researchers investigated whether three short questions that have been validated for detecting depression in adults in general practice were also valid for identifying mild, moderate, and major depression in adolescents.

The researchers interviewed 296 adolescents aged 14 to 16 (including 145 from Denmark and 149 from …
Efficacy and tolerability of fentanyl buccal tablet (FBT) in opioid-tolerant cancer patients with neuropathic pain
Authors: R. Thakur, J. A. Vaughan, J. Messina, F. Xie, D. R. Taylor
Journal: Journal of Clinical Oncology (2007)

19549 Background: Fentanyl buccal tablet (FBT), a new formulation recently approved by the FDA for opioid-tolerant patients with cancer-related breakthrough pain (BTP), provides rapid-onset analgesia. Neuropathic pain is the primary pain pathophysiology in a significant proportion of patients with chronic cancer pain; therefore, the efficacy and safety of FBT was studied in this subpopulation. Methods: The efficacy and safety of FBT in the treatment of BTP in opioid-tolerant cancer patients with neuropathic pain were evaluated as a sub-analysis of two randomized, double-blind, placebo-controlled studies. Of the 45 patients in the sub-analysis (50% male, 86% white, mean age 56 years), 30 identified an effective FBT dose during open-label titration and were randomly assigned to double-blind crossover dose sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) and pain relief (PR) were recorded at intervals after dosing. The primary efficacy measures were the sum of pain intensity differences (PIDs) for the first 30 (SPID 30 ) and 60 minutes (SPID 60 ); secondary efficacy measures included PIDs, PR, and total pain relief (TOTPAR). Use of supplemental BTP medication and adverse events (AEs) were recorded. Results: Combined data (all values mean ±SD) favored FBT vs placebo for SPID 30 (3.35±3.11 vs 1.88±2.58) and were significant for SPID 60 (9.90±7.19 vs 5.51±6.06; 95% CI, 2.99, 5.81). There was a greater reduction in PI following FBT vs placebo at 10 minutes (PID, 0.55±0.89 vs 0.24±0.48), which continued through observation periods of up to 2 hours (3.43±2.44 vs 1.95±1.99). Higher PR scores were noted following FBT vs placebo at 10 minutes (0.43±0.39 vs 0.21±0.28), which continued for up to 2 hours (1.99±0.72 vs 1.36±0.60). TOTPAR was better following FBT vs placebo at 15 (0.88±0.89 vs 0.48±0.73), 30 (2.42±1.85 vs 1.40±1.65), 45 (4.29±2.90 vs 2.61±2.68), and 60 minutes (6.34±4.02 vs 3.94±3.81). Patients were more than twice as likely to require supplemental opioids for BTP episodes following placebo vs FBT. AEs were typical for opioids; e.g., headache (23%), nausea (18%), dizziness (18%), vomiting (14%), and fatigue (11%). Conclusions: FBT was effective and well tolerated in a subgroup of cancer patients with BTP in association with chronic neuropathic pain. No significant financial relationships to disclose.
Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents.
Authors: C. De Lorenzo, G. Riccio, C. Fedele, G. Esposito, E. Di Pietro, G. Schiattarella, C. Coppola, R. V. Iaffaioli, N. Maurea, G. D'Alessio
Journal: Journal of Clinical Oncology (2010)

e11054 Background: Herceptin (H), an anti-ErbB2 humanized antibody prescribed for treatment of ErbB2-positive breast cancer, has proved to be an essential tool in immunotherapy. However, large-scale clinical studies with H have shown that it engenders cardiomyopathy, particularly in patients treated either concurrently or previously with anthracyclines. Two novel human antitumor immunoconjugates were engineered in our laboratory by fusion of a human anti-ErbB2 scFv, Erbicin, with either a human RNase or the Fc region of a human IgG1, and thus called Erb- hRNase and Erb-hcAb (human anti-ErbB2-compact antibody), respectively. Both immunoagents are selectively cytotoxic for ErbB2-positive cancer cells in vitro and vivo. The Erbicin-derived immunoagents (EDIA) target on breast cancer cells an ErbB2 epitope different from that of H. We report that EDIA did not show in vitro cardiotoxic effects on rat and human cardiomyocytes, whereas H was strongly toxic. Methods: Methods for measuring cardiac function in M-mode with shortening fraction (FA) and in B-mode with ejection fraction are not very sensitive in detecting early myocardial damage. In this study we evaluated myocardial strain by speckle tracking technique (ST) by Color Doppler echocardiography (Visual sonic Vevo 2100) to identify early left ventricular dysfunction in mice treated with EDIA, doxorubicin (D), H, their associations and in a sham group. We measured ST and FA by assessing M-mode short axis projection in C57BL/6 mice at time 0, 2 and 6 days of daily administration. Results: EDIA did not impair cardiac function in vivo in a mouse model whereas H significantly reduced radial strain at 3 days of treatment and fractional shortening (% FS) at 6 days of treatment compared to the sham group in a fashion similar to D. Similarly, cardiac fibrosis, an index of collagen accumulation following cardiac muscle deterioration, was significantly attenuated in mice treated with either Erb-hcAb or Erb-hRNase as compared to those treated with H or D. Conclusions: These results suggest that the Erb-hcAb and the immuno RNase are immunoagents which can fulfil the therapeutic need of patients ineligible to H treatment due to cardiac dysfunction. No significant financial relationships to disclose.
Zika, and rapid diagnostic tests for malaria
Authors: Fiona Godlee
Journal: BMJ (2016)

A year ago few people outside French Polynesia had heard of Zika. Now few people in the world will not have heard of it. This relatively benign and largely asymptomatic infection has spread to 25 countries, apparently bringing with it microcephaly, a condition now haunting thousands of families in—and travelling from—Latin America, the Pacific islands, and elsewhere (Cape Verde).

As Daniel Lucey explains in his editorial (doi:10.1136/bmj.i781), the guidance is clear and unanimous on what precautions people should take to prevent transmission to an unborn child. But the absence of an effective diagnostic test bedevils efforts to contain …
Misunderstanding of prostate cancer (CaP) among African American (AA) men of lower socioeconomic status (Lo-SES)
Authors: E. M. Nelson, G. Fraser, A. F. Connors, M. J. Barry, M. Krahn, M. R. Conaway, R. Bashore, A. Wolf, K. L. Kilbridge
Journal: Journal of Clinical Oncology (2006)

6114 Background: CaP disproportionately affects AA men. The objective of this investigation was to assess understanding of the prostate and CaP among Lo-SES, predominantly AA men. Methods: We performed cross sectional, semistructured interviews of 105 men, age 40 and older, in two low-income medical clinics. CaP knowledge was assessed using a subset of questions by Mercer et al. Can J of Public Health 88(5):327, 1997. Patients were shown two male anatomic figures and asked to identify the prostate, bladder, bowels, and penis: 1) Please point to the _____ on the picture of the man. 2) What does the ____ do? Patients’ understanding of sexual, urinary, and bowel function was evaluated using semi-qualitative methods coded by two independent investigators. Demographic data were collected and literacy measured using REALM. Results: Patients’ median age was 58 and 87% self-identified their race as AA. Median annual household income was $16,000. Median reading level was 4th-6th grade. Although 87% of patients had heard of the prostate, only 24% could locate the prostate, and 3% could explain prostate function. Because many men learn about the prostate in the context of CaP screening during physical exam, 23% of patients thought the prostate was synonymous with prostate cancer, 15% of patients believed the prostate is located in the rectum and 4% confused prostate cancer with colorectal cancer. Prostate cancer knowledge was poor and the concept of a risk factor was not understood well. Only 7% could name a single risk factor for CaP including 3% who named race. Just 22% of men cited surgery or radiation therapy as treatments for CaP and 11% could name a side effect of early CaP treatment. Domain confusion was common: 43% of patients confused bowel function with urinary function, 21% confused urinary with sexual function, and 20% confused bowel with sexual function. Conclusions: Baseline understanding of CaP, anatomy, bowel, urinary, and sexual function is poor among older, lo-SES AA men. Substantial patient education is required for CaP screening and treatment efforts in this population with consideration for low literacy. [Table: see text]
Alphavirus immunotherapy of NPM/ALK+ anaplastic large cell lymphoma in a mouse model
Authors: M. N. Brackin, L. A. Miller, N. K. Hutson, S. W. Morris, G. H. MacDonald
Journal: Journal of Clinical Oncology (2004)

2574 Background: \(\underline{\mathrm{A}}\)naplastic \(\underline{\mathrm{L}}\)arge \(\underline{\mathrm{C}}\)ell \(\underline{\mathrm{L}}\)ymphoma (ALCL) is a non-Hodgkin's lymphoma. 2/3 of Kit+ (CD30) ALCL cases are associated with the expression of the fusion oncogene, NPM/ALK. Due to the effective immunogenicity of Venezuelan equine encephalitis virus replicon particles (VRP) expressing foreign antigens, we propose that VRP expressing a mutated form of NPM/ALK (NPM/ALK-VRP) will protect against tumor establishment and induce tumor regression in a murine model of ALCL. Methods: Stably transformed NPM/ALK pro-B cells inoculated intravenously into syngeneic immune competent mice resulted in tumor growth with 50–70% mortality at 2 months and a second phase of death at 4–6 months. To protect against tumor establishment, mice were inoculated in the footpad with NPM/ALK-VRP or GFP-VRP as an irrelevant antigen, boosted 3 weeks later and challenged with tumor cells. To test tumor regression, naive mice were transfused with tumor cells and 2-days later inoculated with either PBS, GFP-VRP or NPM/ALK-VRP, followed by a boost 3 weeks later. In both experiments, mice were scored for mortality (% survival) and morbidity; clinical ranking of 1–6 (6 = no symptoms and 1= death) and weight loss. Results: Immunohistological analysis confirmed the expression of NPM/ALK in tumors. Pre-treatment of mice with NPM/ALK-VRP compared to GFP-VRP significantly increased survival following tumor transfer (80%, 10%, respectively; Chi Square, P=0.0077). In addition, the NPM/ALK-VRP group had an overall higher clinical score and less weight loss compared to the GFP-VRP group. In the regression experiment, both NPM/ALK-VRP and GFP-VRP treated mice had significantly increased survival compared to the PBS group at 3 months post tumors (100%, 100% and 35%, respectively; Chi Square, P<0.0001), higher clinical scores and less weight loss. Conclusions: Pre-treatment of mice with NPM/ALK-VRP protected against tumor establishment. When administered after tumor transfer, treatment with VRP significantly reduced mortality and morbidity, regardless of the antigen expressed. No significant financial relationships to disclose.
Abstract 14883: Remodeling of the Mononuclear Phagocyte Network Underlies Chronic Inflammation and Disease Progression in Heart Failure: Importance of the Cardiosplenic Axis
Authors: Mohamed Ameen Mohamed Ismahil, Tariq Hamid, Shyam S Bansal, Justin R Kingery, Sumanth D Prabhu
Journal: Circulation (2013)

Rationale:  The role of mononuclear phagocytes in chronic heart failure (HF) is unknown.   Objective:  To comprehensively evaluate monocytes/macrophages and dendritic cells (DCs) in HF and the contribution of the spleen to this network and to cardiac remodeling.   Methods and Results:  C57Bl/6 mice underwent coronary ligation and were evaluated after 8 weeks in the context of chronic HF. As compared with sham-operated controls, HF mice exhibited: 1) increased pro-inflammatory CD11b+F4/80+CD206– macrophages in the heart and pro-inflammatory CD11b+F4/80+Ly6C/Gr-1hi monocytes in peripheral blood, and a diminished CD11b+F4/80+Ly6C/Gr-1hi monocyte reservoir in the spleen, 2) significantly augmented CD11c+B220– classical DCs (cDCs) and CD11c+/lowB220+ plasmacytoid DCs (pDCs) in both the heart and spleen, increased cDCs in peripheral blood, and increased pDCs in the bone marrow, and 3) profound splenic remodeling with more abundant white pulp follicles, variability of follicular size, and markedly increased size of the marginal zone and germinal centers. Splenectomy in mice with established HF reversed long-term cardiac remodeling. Adoptive transfer of splenocytes from mice with HF, but not from sham-operated mice, induced long-term cardiac dilatation, dysfunction, and fibrosis in normal syngeneic recipient mice. Recipient mice also exhibited monocyte activation and splenic remodeling similar to HF mice.   Conclusions:  Activation of the mononuclear phagocyte network is central to the progression of cardiac remodeling in HF and heightened antigen processing in the spleen plays a critical role in this process. Splenocytes (presumably splenic monocytes and DCs) promote immune-mediated injurious responses in the failing heart, and retain this immune memory upon adoptive transfer.
Phase I trial of an implanted battery-powered, programmable drug delivery system for continuous doxorubicin administration.
Authors: N J Vogelzang, M Ruane, T R DeMeester
Journal: Journal of Clinical Oncology (1985)

A second generation, implantable drug administration device (DAD, Medtronic, Inc, Minneapolis) which contains a 20-mL drug reservoir, a lithium-thionyl-chloride battery, a peristaltic roller pump, a microprocessor circuit, and an acoustic transducer has entered clinical trials. After surgical placement, drug is entered into and removed from the DAD percutaneously through a Silastic "fill port" using a standard gauge needle and syringe. The pump is noninvasively programmed using a hand-held telemetry wand to administer the drug in a continuous infusion, bolus, or bolus-delay mode. Because of the apparent improved therapeutic index of continuous-infusion doxorubicin (CID), a phase I trial of the Medtronic DAD with CID was begun. Thirteen pumps in 13 patients have functioned for a median of 153 days (range, 11 to 395 days) with one pump still functioning. Four pumps ceased function at 170, 278, 331, and 370 days, respectively; there was a catheter-tip clot on one of the pumps that later malfunctioned. All other pumps functioned until the death of the respective patients. In 84 pump refills, without drug extravasation, the median drug delivery error (actual residual volume--calculated residual volume/calculated residual volume X 100%) was 14%. Doxorubicin was compatible with all components of the drug pathway and did not significantly decompose during two weeks in the drug reservoir. The starting dose of CID was 2.0 mg/m2/d and the maximum tolerated dose was 4.1 mg/m2/d (range, 3.5 to 5.5). A median cumulative doxorubicin dose of 244 mg/m2 per patient (range, 10 to 583 mg/m2) has been infused.(ABSTRACT TRUNCATED AT 250 WORDS)
指南--2型糖尿病的治疗：英国国家医疗卫生和临床技术优选研究所最新指南概要
Authors: Philip, Home, Jonathan, Mant, Jose, Diaz, Claire, Turner, 刘哲隆, 肖新华
Journal: BMJ (2008)

为什么阅读本概要？ 2型糖尿病的患病率迅速攀升。全球估计有超过240000000例糖尿病患者，2030年这个数字可能达到360000000例。糖尿病对健康的影响主要是心血管疾病，但随着发病年龄的年轻化和对心血管疾病预防措施的进步，糖尿病患者发生微血管损害的风险升高，如肾脏和眼部疾病。
Interstitial Lung Disease Associated with Erlotinib/Gemcitabine Therapy in Patients with Pancreatic Cancer
Authors: Shigeru Tanaka, Tomoya Shimokata, Hiroaki Tsukuura, Osamu Maeda, Ayako Mitsuma, Eizaburo Ohno, Hiroki Kawashima, Yoshiki Hirooka, Hidemi Goto, Yuichi Ando
Journal: Annals of Oncology (2014)
Parallel Phase I Studies of Daunorubicin Given With Cytarabine and Etoposide With or Without the Multidrug Resistance Modulator PSC-833 in Previously Untreated Patients 60 Years of Age or Older With Acute Myeloid Leukemia: Results of Cancer and Leukemia Group B Study 9420
Authors: Edward J. Lee, Stephen L. George, Michael Caligiuri, Ted P. Szatrowski, Bayard L. Powell, Sheila Lemke, Richard K. Dodge, Ruth Smith, Maria Baer, Charles A. Schiffer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The Cancer and Leukemia Group B conducted parallel phase I trials of cytarabine, daunorubicin, and etoposide (ADE) with or without PSC-833 (P), a modulator of p-glycoprotein–mediated multidrug resistance. PATIENTS AND METHODS: One hundred ten newly diagnosed patients ≥ 60 years of age with de novo acute myeloid leukemia (AML) were treated. All patients received cytarabine by continuous infusion for 7 days at 100 mg/m 2 /d. The starting dose of daunorubicin was 30 mg/m 2 /d for 3 days. Etoposide was administered at a dose of 100 mg/m 2 /d for 3 days, except in the last cohort administered ADEP, who received 60 mg/m 2 . PSC-833 was given intravenously with a loading dose of 1.5 mg/kg over 2 hours and a simultaneous continuous infusion of 10 mg/kg/d continued until 24 hours after the last dose of daunorubicin or etoposide. RESULTS: There was no toxicity attributed to the PSC-833. Dose-limiting toxicity was primarily gastrointestinal (diarrhea, mucositis in the ADEP group). The estimated maximum-tolerated doses, calculated using a logistic regression model, were daunorubicin 40 mg/m 2 /d for 3 days with etoposide 60 mg/m 2 for 3 days in the ADEP group and daunorubicin 60 mg/m 2 /d for 3 days and etoposide 100 mg/m 2 /d for 3 days in the ADE group. Twenty-one (48%) of 44 patients achieved complete remission with ADE, compared with 29 (44%) of 66 patients treated with ADEP. CONCLUSION: It is necessary to decrease the doses of daunorubicin and etoposide when they are administered with PSC-833, presumably because of the effect of the modulator on the pharmacokinetics of these agents. A phase III trial comparing the regimens derived from this phase I trial has recently begun.
Human placenta at mid-term gestation is a source of hematopoietic progenitors cells of unusual CD45-/CD34-phenotype.
Authors: Laure Croisille, Salomon Yap, Alison Logar, Mihaela Crisan, Bin Sun, Pang-Ning Teng, Eric Lagasse, Bruno Peault, Louis Casteilla
Journal: Blood (2006)
Excision repair cross complementing 6 (ERCC6) single nucleotide polymorphism (SNP) and outcome to gemcitabine (gem)/cisplatin (cis) or docetaxel (doc)/cis in stage IV non-small cell lung cancer (NSCLC) patients (pts)
Authors: O. Etxaniz, M. Provencio, J. Terrasa, A. Carrato, P. Lianes, I. Bover, M. Perez-Cano, J. Sanchez, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2007)

7605 Background: ERCC6 (alternate name CSB) is involved in both transcription coupled and base excision DNA repair, and the ERCC6 C-6530&gt;G SNP is involved in gene regulation. Different levels of ERCC6 mRNA expression have been observed in cells according to ERCC6–6530 genotype. Methods: We investigated the ERCC6 C-6530&gt;G SNP in 309 stage IV NSCLC pts treated with doc/cis (196 pts) and gem/cis (113 pts). DNA was extracted from peripheral lymphocytes and Taqman assay was used for SNP typing. Results: Distribution of ERCC6 genotypes was: CC 113 pts (36.6%); CG 157 pts (50.8%); GG 39 pts (12.6%). No differences in genotype were observed according to age, gender, performance status (PS), histology, chemotherapy regimen or second-line treatment. Overall time to progression (TTP) was 5.4 months (m) and median survival (MS) 9.9 m. No differences in TTP or MS were observed according to ERCC6 SNP types. However, when pts were broken down by chemotherapy regimen, TTP was 7 m for 31 CC pts treated with gem/cis and 5.4 m for 71 CC pts treated with doc/cis (P=0.04) ( Table ). MS was longer for CC pts treated with gem/cis (11 m) than for CC pts treated with doc/cis (8.9 m) (P=0.46). Differences were also observed in pts with PS 0 and in younger pts. Conclusions: ERCC6 C-6530&gt;G SNP may confer differential sensitivity to gem or doc in combination with cis. We hypothesize that ERCC6 6350 CC is a surrogate of ERCC6 transcript, where lower ERCC6 expression levels may increase the activity of gem/cis in comparison to doc/cis. No significant financial relationships to disclose. [Table: see text]