tbuckley/cabot-search huggingface dataset:
Pegylated liposomal doxorubicin in recurrent high-grade glioma: Comparison of clinical trial results and compassionate use
Authors: M. Glas, H. Koch, B. Hirschmann, T. Jauch, A. Steinbrecher, U. Bogdahn, P. Hau
Journal: Journal of Clinical Oncology (2007)

2073 Background: Results from prospective clinical studies may not always be reproduced in clinical practice. Therefore it is important to compare data from clinical trials with data from compassionate use of the same treatment. Here, we present patients with relapsed high-grade glioma treated outside a clinical trial with liposomal pegylated doxorubin (PEG-DOX). Methods: This data was documented prospectively and compared to our earlier published study results. Forty-nine patients with recurrent high-grade glioma (WHO III: n=18; IV: n=31) were treated with PEG-DOX (days 1 and 14/28, 20 mg/m 2 ) alone or in combination therapy with temozolomide (TMZ) (days 1 to 5/28, 200 mg/m 2 ). The clinical response rate, time to progression, progression free survival and overall survival were evaluated. Results: The overall response rate including disease stabilization was 53% (WHO III: 61; IV: 48). PFS-6 was 27% (WHO III: 33%; IV: 23%). The median OS after initiation of PEG-DOX was 35 weeks (WHO III: 68; IV: 31). Comparison of PEG-DOX monotherapy and combination therapy revealed no significant difference. Both regimens were well tolerated, with the main side effect being hematologic toxicity (grade 1–2: 8%, grade 3–4: 18%). Conclusion: These data compare favorably with published data and underline the potential of PEG-DOX in this setting. In addition, the prolonged median OS after initiation of PEG-DOX for grade III-tumors (68 weeks) merits additional focus. No significant financial relationships to disclose.
A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer
Authors: Zhaoling Dan, Haiqiang Cao, Xinyu He, Zhiwen Zhang, Lili Zou, Lijuan Zeng, Yan Xu, Qi Yin, Minghua Xu, Dafang Zhong, Haijun Yu, Qi Shen, Pengcheng Zhang, Yaping Li
Journal: Theranostics (2016)

Cancer metastasis is the leading reason for the high mortality of breast cancer.Herein, we report on a pH-responsive host-guest nanosystem of succinobucol (PHN) with pH-stimuli controlled drug release behavior to improve the therapeutic efficacy on lung metastasis of breast cancer.PHN was composed of the host polymer of β-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (βCD-DPA), the guest polymer of adamantyl end-capped methoxy poly(ethylene glycol) (mPEG-Ad), and the active agent of succinobucol.PHN comprises nanometer-sized homogenous spherical particles, and exhibits specific and rapid drug release in response to the intracellular acidic pH-stimuli.Then, the anti-metastatic efficacy of PHN is measured in metastatic 4T1 breast cancer cells, which effectively confirms the superior inhibitory effects on cell migration and invasion activities, VCAM-1 expression and cell-cell binding of RAW 264.7 to 4T1 cells.Moreover, PHN can be specifically delivered to the sites of metastatic nodules in lungs, and result in an obviously improved therapeutic efficacy on lung metastasis of breast cancer.Thereby, the pH-responsive host-guest nanosystem can be a promising drug delivery platform for effective treatment of cancer metastasis.
DNA Demethylation Activity Over Time and Safety Of 3 Different Dose-Escalation Regimens Of SGI-110, a Novel Subcutaneous (SQ) Hypomethylating Agent (HMA), In The Treatment Of Relapsed/Refractory Patients With MDS and AML
Authors: Gail J. Roboz, Jean-Pierre Issa, David Rizzieri, Wendy Stock, Casey O'Connell, Karen Yee, Raoul Tibes, Elizabeth A. Griffiths, Katherine Walsh, Eric J. Feldman, Ellen Ritchie, Arati V. Rao, Richard A. Larson, Guillermo Garcia-Manero, Farhad Ravandi, Elias Jabbour, Jorge E. Cortes, Aaron Schimmer, Ruben A. Mesa, William Blum, Woonbok Chung, Sue Naim, Pietro Taverna, Yong Hao, Gavin Choy, Mohammad Azab, Hagop M. Kantarjian
Journal: Blood (2013)
Pazopanib and lapatinib in patients with relapsed malignant glioma: Results of a phase I/II study
Authors: S. N. Frentzas, M. D. Groves, J. Barriuso, D. Harris, D. Reardon, M. C. Curtis, A. B. Suttle, B. Ma, J. J. Lager, J. S. de Bono
Journal: Journal of Clinical Oncology (2009)

2040 Background: Pazopanib (paz) is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-kit; and lapatinib (lap) is an oral tyrosine kinase inhibitor of EGFR (ErbB1) and HER-2 (ErbB2). Combination of VEGFR, PDGFR, and ErbB1 inhibitors may provide synergistic antitumor activity in malignant glioma. Phase I determined the optimally tolerated regimen (OTR) of paz and lap when given with enzyme-inducing anticonvulsants (EIACs). Phase II, which evaluated the efficacy of daily paz/lap (400 mg/1000mg) in relapsed grade 4 glioma without EIACs, was previously reported. Methods: Patients (pts) with grade 3 or 4 glioma, on EIACs, and with adequate organ function were eligible. Doses of paz and lap were escalated in a 3 + 3 design. OTR was defined as the highest dose of paz/lap at which no more than 1 of 6 pts had dose limiting toxicity (DLT) and target concentrations were achieved. Results: 32 pts have been enrolled at doses of paz/lap (mg, daily unless specified) of 200/1500 (N = 4), 800/1500 (N = 6), 800/500 bid (N = 5), 800/750 bid (N = 7), 800/1000 bid (N = 6), and 600 bid/1000 bid (N = 4). Data on 28 pts: the most common adverse events (AEs) were: fatigue (25%); diarrhea (25%); headache (21%); ALT increase (18%); nausea (18%); and insomnia (14%). Hepatobiliary lab abnormalities were reversible, uncomplicated, and included: AST elevation (11%), hyperbilirubinemia (7%), ALT elevation (36%; 7% Gr 3), and Alk phos elevation (14%). DLTs were elevated liver enzymes (800/1500; 1 pt), elevated lipase (800/750 bid; 1 pt) and thrombocytopenia, fatigue, diarrhea, confusion (800/1000 bid; 1 pt). 2 pts dose reduced and 3 pts had a dose interruption. At 600 bid/1000 bid, the target paz Cmin of 17.5 μg/mL was achieved; median lap Cmin of 0.447 μg/mL approached the target of 0.5 μg/mL. Phase I best response (MacDonald criteria) was PR in 3 pts (11%) and SD ≥ 8 weeks in 5 pts (18%). Two pts remain on the phase II, at 21 months (PR) and 23 months (CR) of therapy. Conclusions: The paz/lap combination has a manageable safety profile with a preliminary OTR with EIACs of paz 600 mg bid/ lap 1000 mg bid. EIACs decreased plasma paz and lap concentrations. Responses and lengthy periods without disease progression were seen in some pts in phase I and II. [Table: see text]
Demonstration of &lt;italic&gt;Herpesvirus saimiri&lt;/italic&gt;-Associated Antigens in Peripheral Lymphocytes From Infected Marmosets During &lt;italic&gt;In Vitro&lt;/italic&gt; Cultivation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lawrence A. Falk, Lauren G. Wolfe, John Hoekstra, Friedrich Deinhardt
Journal: JNCI Journal of the National Cancer Institute (1972)

Peripheral lymphocytes from white-lipped (Saguinus fuscicollis and S. nigricollis) marmosets infected with Herpesvirus saimiri (HVS) were separated from whole blood on Ficoll-Hypaque gradients. The cells were cultivated in vitro in suspension or with susceptible vero cells (a continuous line of African green monkey kidney cells) and were examined for infectious HVS and HVS-associated antigens. HVS antigens were not demonstrated in smears of lymphocytes immediately after removal from the marmosets, but lymphocyte smears examined after 24, 48, and 72 hours' cultivation showed that 1–5% of the lymphocytes contained stainable HVS antigens. Infectious HVS was not recovered from super-natants or cell-free extracts of lymphocyte suspensions after cultivation up to 120 hours, and herpes-type particles were not seen by electron microscopy in lymphocytes cultured up to 72 hours. HVS antigens developed in lymphocytes 24 hours after cocultivation with vero cells, and already a small percentage of lymphocytes had transferred the HVS genome in some form to the vero cells. HVS was recovered from supernatants and cell-free extracts of cocultivation cultures 48–72 hours after incubation.
Overall Survival Analysis of Stage Iv Non Small Cell Lung Cancer with Synchronous Isolated Metastasis in a Large Retrospective Cohort of 4935 Patients with Lung Cancer
Authors: A.C. Toffart, M. Duruisseaux, H. Nagy-Mignotte, L. Sakhri, P.Y. Brichon, J. Villa, D. Hoffmann, P. Guillem, J.F. Timsit, D. Moro-Sibilot
Journal: Annals of Oncology (2014)
Pathogenesis of Dimethylnitrosamine-Induced Hepatocellular Cancer in Hamster Liver and Lack of Enhancement by Phenobarbital&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: F Stenbäck, H Mori, K Furuya, G M Williams
Journal: JNCI Journal of the National Cancer Institute (1986)

The early stages of dimethylnitrosamine (CAS: 62-75-9)-induced liver cancer and the effect of administration of phenobarbital (CAS: 50-06-6) after dimethylnitrosamine were studied in Syrian golden hamsters. A single ip injection of 6 mg dimethylnitrosamine/kg (body wt) induced hepatocellular altered foci by 6 months. Most foci were composed mainly of large clear glycogen-containing cells, while smaller numbers were formed by cells with abnormally acidophilic or basophilic cytoplasms. Biliary cysts, but not biliary neoplasms, also occurred. A few neoplastic (hyperplastic) nodules and hepatocellular carcinomas developed by 12 months. gamma-Glutamyltranspeptidase activity was not present in any of the hepatocellular lesions, but foci of all types, neoplastic nodules, and carcinomas were characterized by a lack of iron accumulation. Phenobarbital at 0.05% in the diet for up to 12 months did not increase the number of lesions of any type, indicating a lack of promoting effect under these conditions.
Combination chemotherapy followed by chemoradiation for stage III pancreatic adenocarcinoma (PA)
Authors: S. Cereda, M. Reni, P. Passoni, A. Rognone, E. Mazza, R. Nicoletti, A. Zerbi, G. Balzano, V. Di Carlo, E. Villa
Journal: Journal of Clinical Oncology (2008)

15667 Background: Role and timing of chemotherapy and radiation for treating stage III PA remains controversial. This current study evaluated the outcome of sequential chemotherapy followed by chemoradiation. Methods: Treatment-naive patients (pts) with 18–75y, performance status >50 and stage III PA not amenable to curative resection according to National Comprehensive Cancer Network guidelines, were treated with either PEFG/PEXG (cisplatin, epirubicin, 5fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (same as above with docetaxel substituting epirubicin). Pts without evidence of progression (PD) after a maximum of 6 months of chemotherapy received chemoradiation (50–60 Gy) with concurrent F or X. Results: Between October 1997 and December 2006, 79 pts (44 males; 56%) were treated at a single institution. Median age was 63y, median PS 1. CA19.9 was higher than normal in 66 pts (84%). Fifty-six pts (70%) received planned chemoradiation, while 23 did not due to: PD (N=16 (20%); 4 isolated local failure) during or immediately after chemotherapy; refusal (6); pathologic complete remission (1). Median survival (OS) was 16.5 months; 2y and 5y OS was 19% and 5%. Median progression-free (PF) survival was 10.5 months: 10 pts (13%) were PF; isolated local failure was observed in 21 pts (27%); 12 pts (15%) had both local and distant failure; 25 pts (32%) developed extra-pancreatic metastases without local PD; site of recurrence was unknown in 11 (14%). Chemotherapy reduced CA19.9 by >89% in 26 pts (39%) and by 50–89% in 22 (33%). Partial response was observed in 38 pts (48%) and stable disease in 32 (41%). Median OS was 17.0 months for responders, 12.2 months for pts with stable disease (p=.01) and 6.0 months for those with PD. Among responders, 11 were submitted to radical surgery and had a significantly longer OS with respect to 27 pts who remained not amenable to resection (2y OS 58% versus 12%; p=.025). Conclusions: A strategy of combination chemotherapy with 4-drug regimens followed by chemoradiation showed promising results for treatment of stage III PA. Most pts developed extra-pancreatic metastases while isolated local failure during chemotherapy was a rare event. Radiological response predicted OS. No significant financial relationships to disclose.
If You Can’t Measure Performance, Can You Improve It?
Authors: Robert A. Berenson
Journal: JAMA (2016)

Coauthor Pinka Chatterji, PhD, said it appears that maternal depression related to having to return to work early is transitory.For some women, returning to work might actually relieve stress by providing structure, income, and even enjoyment, said Chatterji, an associate professor of economics at the University of Albany.However, "on average, mothers would benefit from having access to longer leave," she said.Although only a dream for most, 6 months seems to be the optimal maternity leave duration
Northern Ireland’s abortion law breaches human rights, court rules
Authors: Clare Dyer
Journal: BMJ (2015)

The virtual ban on abortion in Northern Ireland is a breach of the European Convention on Human Rights, a High Court judge has declared in a historic ruling.

Mr Justice Horner ruled that the law violated the convention in denying abortions in cases where the fetus had a fatal abnormality or where the woman or girl was pregnant as a result of rape or incest.

The ruling at the High Court in Belfast came after years …
Genetic Determinants of Drug Resistance in <i>Mycobacterium tuberculosis</i> and Their Diagnostic Value
Authors: Maha R. Farhat, Razvan Sultana, Oleg Iartchouk, Sam Bozeman, James Galagan, Peter Sisk, Christian Stolte, Hanna Nebenzahl-Guimaraes, Karen Jacobson, Alexander Sloutsky, Devinder Kaur, James Posey, Barry N. Kreiswirth, Natalia Kurepina, Leen Rigouts, Elizabeth M. Streicher, Tommie C. Victor, Robin M. Warren, Dick van Soolingen, Megan Murray
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of antituberculosis drugs.
Questions about a Placebo-Controlled Trial of Preventive Therapy for Tuberculosis in HIV-Infected Ugandans
Authors: M T Turner
Journal: New England Journal of Medicine (1998)

The study of HIV-seropositive and PPD-positive Ugandan adults included a placebo group of almost 500 persons.  The Journal apparently was influenced to publish this study despite reservations because it had been approved by the institutional review board of University Hospitals of Cleveland and Case Western Reserve University and all the patients gave informed consent.  It is hard to believe that a similar study of coinfected adults in Cleveland would ever have been approved by the same institutional review board.  Just what is it that makes such a study possible in Kampala Uganda?  The women in the study were of childbearing age and close to 70% of the participants were women.  There was a total of 31 cases of tuberculosis in the placebo group.  Not only were adults unnecessarily included in a placebo group but their children were also exposed and possibly infected as a necessary consequence of this ethically flawed study.  (full text)
Risk of atherosclerotic disease coronary artery lesions in childhood cancer survivors.
Authors: D. C. Landy, T. L. Miller, G. V. Lopez-Mitnik, S. R. Lipsitz, A. S. Hinkle, L. S. Constine, C. A. French, A. M. Rovitelli, M. J. Adams, S. E. Lipshultz
Journal: Journal of Clinical Oncology (2010)

e19586 Background: Increases in several traditional risk factors for atherosclerotic disease (AthD) such as cholesterol may partially explain the recently documented increased incidence of early cardiovascular disease (CVD) in survivors. The ability to aggregate these traditional risk factors into a single measure of AthD risk may not only help identify the cause of increased early CVD in survivors but also improve the interpretation of traditional risk factor testing. This has recently become possible using the NIH Pathobiological Determinants of Atherosclerosis Study's risk scoring system (PDAY) that predicts risk of an AthD coronary artery lesion in 15- to 34-yr olds. Methods: Risk factors were measured in a representative sample of 101 survivors and 31 siblings from 15-34 yrs old in an NCI prospective cohort study in Rochester, NY from 1999-2004. Risk factors were aggregated using PDAY, a weighted combination of age, sex, total cholesterol, HDL-cholesterol, smoking, systolic BP, hyperglycemia, and BMI. Survivors were compared to siblings after adjusting for age and sex. Results: Survivors were a mean 14 yrs from diagnosis; 57% received anthracyclines, 41% cardiac radiation, 48% cranial radiation, and 5% total body radiation as part of multiagent therapy. Survivors had similar AthD lesion risk as siblings (p = .83) which increased for males and by age. Conclusions: Similar estimates of AthD risk between survivors and siblings suggests much of the increase in early CVD incidence observed in follow-up studies of survivors is due to the direct effects of cancer treatment such as radiation exposure. Total CVD risk is a combination of this increased risk and that due to traditional risk factors. PDAY provides clinicians caring for survivors a new easy to use and cost free tool to assess the latter. Thus, PDAY may improve survivorship care by increasing understanding of how traditional AthD risk factors predispose to future CVD, identifying survivors requiring further assessment, and hopefully increasing compliance with risk reduction strategies. Mean (range) PDAY risk estimate of AthD lesions for survivor subgroups 15-24-yr-old females 15-24-yr-old males 25-34-yr-old females 25-34-yr-old males <1% (0-8%) 3% (0-24%) 9% (3-26%) 18% (7-42%) No significant financial relationships to disclose.
Sources of information on decisions regarding contralateral prophylactic mastectomy: A prospective study.
Authors: Katharine Yao, Kristen Wroblewski, Martha Van Haitsma, Sarah Rabbitt, Jordan Williams, Swati Kulkarni
Journal: Journal of Clinical Oncology (2014)

75 Background: The rate of contralateral prophylactic mastectomy (CPM) has increased but little is known about the sources of information women utilize to choose CPM. Methods: A 55-item survey validated with breast cancer survivors was administered to 136 patients before surgery from two institutions. Results: The median age was 58 years (range 30-85). Eighty-three (69.2%) were White. Seventy-five (58.6%) had a lumpectomy, 41 (32%) a unilateral mastectomy and 12 (9.4%) had a CPM. About 80% of women felt the information they were given about breast cancer treatment was consistent. Fifty-five patients (41.7%) sought out extra information beyond what the doctor gave them. Information with the strongest influence was websites, books recommended by their doctor (44%) and websites, books not recommended by their doctor (30.4%) was the second strongest influence. Women ranked their doctor’s spoken advice as the most important source of information (74.3%) compared to advice from individuals outside of medicine, online information, observing breast cancer survivors and advice from friends/family. Plastic surgeons and the spouse/partner had more influence on those &lt;50 years old compared to &gt;50 years old (p=0.03). When asked which individual outside of medicine influenced their decision, women chose breast cancer survivors as their top choice compared to their spouse/partner, church leaders and friends/relatives. However, 82 women (62.6%) stated that information provided by staff did not include any information about removing the healthy breast. Forty-one (36%) stated that no one discussed contralateral breast cancer risk and 67 (59%) stated that no one talked with them about the possibility that cancer could turn up somewhere else even if both breasts were removed. Conclusions: Women do not always receive information about CPM from their doctors but they still highly value their doctor’s advice. These findings highlight an opportunity for physicians to educate women about the utility of CPM as part of their surgical treatment.
A phase I/II study of pemetrexed plus cisplatin in Japanese patients with malignant pleural mesothelioma
Authors: K. Gemba, K. Yamazaki, H. Kunitoh, T. Hida, K. Nakagawa, T. Shinkai, Y. Ichinose, Y. Nambu, N. Saijo, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

18152 Background: Pemetrexed (pem) is globally used for the treatment of malignant mesothelioma (MPM) in combination with cisplatin (cis). Pharmacokinetic (PK) difference of pem/cis between Western and Asian population (pop) so far remains unknown. To investigate safety/efficacy of pem/cis therapy and PK profiles of pem/cis for Japanese (Jpn) MPM patients (pts), we designed a phase I/II study. Methods: Primary objectives in phase (Ph) I part were to determine a recommended dose (RD), and in Ph II part were to examine the efficacy of the RD and safety. PK profiles were to be analyzed as a secondary objective. A cohort of 6 pts, starting from a dose of pem 500 mg/m 2 and cis 75 mg/m 2 (level 1: LV1), was used in the dose-escalation Ph I. The efficacy of the RD was to be evaluated in at least 18 pts in the study. Key eligibility criteria were: histologic diagnosis of MPM incurable by surgery, no prior systemic chemotherapy, and a performance status 0–1. Under full vitamin supplementation, pem was administered as a 10-min. infusion on day 1 of a 21-day cycle, followed by cis administration as a 2-hr. infusion 30 min. after pem administration. For comparison of PK profiles, PK data of this study and a Western phase III study were analyzed by pop PK approach. Results: In Ph I, 13 pts were enrolled: 7 in LV1 and 6 in level -1 (LV-1: pem 500 mg/m 2 and cis 60 mg/m 2 ). Two dose-limiting toxicities were observed in LV1: pneumonitis and neutropenia. The RD were then determined to be LV1. In Ph II, 12 pts were enrolled in LV1. For safety, one drug-related death was reported among 25 pts due to worsening of underlying pneumonia observed before enrollment. The most common G3/4 toxicities were neutropenia and hemoglobin decrease. For efficacy, a partial response was achieved for 7 of 19 pts who received LV1. Response rate was 36.8% (95% CI: 16.3- 61.6). PK profiles of pem/cis in Jpn pts were similar to those in Western. The results of other secondary objectives, e.g., progression-free survival, QOL, and pulmonary function test, will be presented in the conference. Conclusions: The profiles of efficacy/safety/PK shown in this study are almost comparable to those in Western pts, and indicate that pem/cis therapy will be a promising therapy for Jpn MPM pts. No significant financial relationships to disclose.