tbuckley/cabot-search huggingface dataset:
A phase II study of weekly low-dose paclitaxel plus 24-hour infusion of cisplatin as first-line chemotherapy for metastatic breast cancer (MBC)
Authors: Y. Shen, C. Hsu, S. Kuo, Y. Lu, C. Lin, C. Huang, A. Cheng
Journal: Journal of Clinical Oncology (2007)

1100 Background: The dose and schedule of paclitaxel have been evolving in the past 15 years. However, the lowest effective dose of weekly paclitaxel remains unclear. In this study, we examined if a very low dose of paclitaxel can be effective in MBC. Except for the dose of paclitaxel, the chemotherapy regimen and the patient population of this study were very similar to one of our previous report (Cancer 2002; 95:2044–50). Methods: Women with chemotherapy-naïve metastatic BC, adequate performance status and organ functions were eligible. All patients received paclitaxel, 50 mg/m 2 iv 1 hr on D1, 8 and 15, and cisplatin, 40 mg/m 2 iv 24 hrs on D1 and 8, every 4 weeks. Patients continued this low-dose regimen until progressive disease (PD) or prohibitive toxicities occurred. Patients who had PD or stable disease (SD) without clinical benefit were shifted to paclitaxel 80 mg/m 2 iv 1 hr on D1, 8 and 15, and cisplatin, 40 mg/m 2 iv 24 hrs on D1 and 8, every 4 weeks. The primary endpoint was overall response rate (ORR). Simon’s optimal two-stage design (P0, P1,a, and βare 20%, 40%, 0.05, and 0.2, respectively) was adopted. More than 4 objective responses were needed in the first 13 patients, and a total of 43 patients will be enrolled. Results: After a median follow-up duration of 16.5 months, 27 patients were evaluable for response and toxicity. Their median age was 52.7 years (range: 30.1∼69.4). Twenty patients were hormone receptor (+), while 6 patients were Her-2/neu (+). A total of 121 cycles of protocol treatment were administered as of Dec. 2006. There were 0 complete response and 14 partial responses, for an ORR of 51.9%. Nine of 14 responders remain progression-free. The PFS was 9.6 months (95% of CI: 5.53∼13.67%) and the OS not reached. Grade 3–4 anemia, neutropenia, liver toxicity, thrombocytopenia, and skin toxicities were reported in 8, 6, 2, 1, and 1 patients, respectively. Neurotoxicity was common (22/27), but all were grade 1 or 2. Conclusions: The preliminary results of this study suggest that weekly low-dose paclitaxel is as effective as conventional-dose paclitaxel, and the treatment-related toxicities were more acceptable. No significant financial relationships to disclose.
A phase I study of estramustine, weekly docetaxel and carboplatin (EDC) chemotherapy in patients with hormone refractory prostate cancer (HRPC)
Authors: W. K. Oh, E. Hagmann, J. Manola, D. J. George, T. D. Gilligan, M. R. Smith, D. S. Kaufman, P. W. Kantoff
Journal: Journal of Clinical Oncology (2004)

4656 Background: The purpose of this study was to define the maximal tolerated dose (MTD) of weekly docetaxel combined with carboplatin and estramustine in the treatment of patients with HRPC. Methods: Patients with progressive HRPC were eligible. Prior chemotherapy was allowed, except taxanes and platinum drugs. 25 patients were treated with escalating doses (20, 25, 30, 36, 43 mg/m2) of weekly docetaxel on days 2, 9, 16 of a 28-day cycle. Doses of estramustine [140 mg po TID days 1–5, 8–12, 15–19] and carboplatin [AUC (5) on day 2] were fixed. Results: Patient characteristics: median age 64 yrs, PS 0 (33%), 1 (66%), median PSA 117 ng/ml. Prior ketoconazole (53%), mitoxantrone (10%). A total of 3, 3, 3, 4 and 12 patients were treated at each of 5 dose levels of docetaxel. No DLTs were noted. Though MTD was not reached, dose escalation was stopped at the docetaxel dose (43 mg/m2) because of significant activity; 9 additional patients were accrued. No grade 3/4 myelosuppression was seen until this dose level, when 1 patient each developed grade 3 anemia, neutropenia and thrombocytopenia. One patient developed grade 4 thrombocytopenia and two patients grade 4 neutropenia. Of 12 patients treated at this dose level, 7 and 4 patients had maximum grade 3 and 4 toxicities, respectively. Among all treated patients, PSA declines ≥50% occurred in 60%. At the recommended phase II dose, PSA declines ≥50% were seen in 75% (95% C.I., 43–95%). 3 of 14 (21%) total patients with measurable disease had a partial response. Median survival was 14.6 months. Conclusions: EDC is a well-tolerated and active regimen in HRPC. Grade 3/4 toxicity was primarily myelosuppression. The recommended phase II dose of docetaxel is 43 mg/m2 combined with estramustine and carboplatin. PSA declines ≥50% were seen in 75% of patients at the recommended phase II dose, though responses were seen at every dose level. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Pulmonary function testing pre and after allogeneic hematopoietic cell transplantation for hematological malignancies
Authors: Athanasia Pataka, Ioanna Sakellari, Sofia Akritidou, Evdokia Sourla, Eleni Vaitsi, Asimina Paspala, Ioannis Batsis, Despoina Mallouri, Zoi Bousiou, Varnavas Konstantinou, Christos Smias, Panagiotis Kaloyannidis, Michael Iskas, Achilleas Anagnostopoulos, Paraskevi Argyropoulou
Journal: European Respiratory Journal (2014)

Background:Allogeneic hematopoietic stem cell transplantation (alloHCT) may be accompanied with severe pulmonary complications with the deterioration of pulmonary function testing (PFT) as the only early symptom. Aim: To evaluate the prevalence and types of PFT abnormalities in alloHCT patients and their association with Graft-versus-host disease (GVHD).  Methods: Retrospective evaluation of 53 alloHCT recipients aged 39.4±15.2 years, 60.4% males, who underwent PFT before and 6-12 months after alloHCT. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVCratio, Total Lung Capacity (TLC), Residual Volume (RV) and lung diffusion capacity for carbon dioxide (DLCO) corrected for the hemoglobin levels were determined.  Results: A statistically significant reduction was noted in FEV1 (pre-alloHCT of 99.6%±21% vs. post- alloHCT of 88.4% ± 24%, p  Conclusions: PFT should be included to standard periodic examination before and after alloHCT procedure as the lung is a target organ for GVHD.
Characterisation of the vaginal microbiome in cervical intraepithelial neoplasia
Authors: Anita Mitra, David MacIntyre, Yun Lee, Ann Smith, Julian Marchesi, Benjamin Lehne, Ramya Bhatia, Deirdre Lyons, Evangelos Paraskevaidis, Jia Li, Elaine Holmes, Jeremy Nicholson, Phillip Bennett, Maria Kyrgiou
Journal: The Lancet (2016)
A pilot study of IV bevacizumab in hepatocellular cancer patients undergoing chemoembolization
Authors: C. D. Britten, R. S. Finn, A. S. Gomes, R. Amado, L. Yonemoto, G. Bentley, R. Mass, R. W. Busuttil, D. J. Slamon
Journal: Journal of Clinical Oncology (2005)

4138 Background: Transarterial chemoembolization (TACE) provides a modest survival benefit in carefully selected patients with hepatocellular cancer (HCC) [Llovet JM et al, Hepatology 37:429–42, 2003]. After TACE, plasma VEGF levels rise, contributing to neovascularization (NVASC) and tumor re-growth. IV bevacizumab (BV) may inhibit NVASC, thereby improving TACE results. Methods: This pilot study evaluates NVASC using serial angiography in 30 HCC patients undergoing TACE who are randomized to either BV (10 mg/kg IV q 14 days) or observation (OBS), with cross-over to BV allowed after week 14. Angiograms are performed at day 8, week 10, and week 14. TACE is performed at day 8, and at week 14 if indicated. Eligibility criteria include platelets ≥ 60K, transaminases ≤ 5 times upper limit of normal, bilirubin ≤ 2.5 mg/dL, and Child’s class A/B disease. Results: 7 of 10 randomized patients are evaluable (5 BV, 2 OBS). After the first TACE, 1 BV patient had NVASC, but the new vessels did not supply tumor. 2 BV patients required TACE at week 14: one had recannalization, and another had pre-existing vessels not treated at day 8. 1 OBS patient required TACE at week 14 for recannalization and NVASC: he subsequently received BV. 6 patients (5 BV, 1 cross-over) have received BV for a median of 6 months, including 1 patient who remains on BV at 1 year. All patients have experienced transient grade 2 to 4 transaminitis after TACE. BV-related toxicities have included controllable grade 3 hypertension in 3 patients, and transient grade 2 proteinuria in 2 patients. One BV patient with a prior history of varices experienced a grade 3 variceal bleed within 1 week after withdrawing from study. Accrual continues, and analysis of serum angiogenic factors pre- and post-TACE is pending. Conclusions: BV is well tolerated in selected HCC patients undergoing TACE, and prolonged disease control has been achieved in the patients treated to date. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech
Prevalence of <i>CDH1</i> germline mutations in subjects with early onset or familial lobular breast cancer, a multicenter collaboration
Authors: S. Masciari, K. A. Schrader, J. Senz, N. Tung, J. Balmana, A. R. Razzak, P. Miron, D. G. Huntsman, J. E. Garber
Journal: Journal of Clinical Oncology (2009)

11042 Background: Invasive lobular breast carcinoma (LBC) is part of the hereditary diffuse gastric cancer (HDGC) syndrome, associated with germline mutations in the E-cadherin (CDH1) gene. CDH1 mutations can be identified in 80% of families ascertained by DGC. The risk of DGC in CDH1 mutation carriers is 67% in males, and 83% in females; the estimated risk of LBC in women is 39–50% to age 80. Management of HDGC includes prophylactic gastrectomy. In this study, we estimated the prevalence of germline CDH1mutations among women with LBC who were either diagnosed at young age or had family history of breast cancer (BC). Methods: Germline DNA was collected from 383 women with LBC or mixed, lobular/ductal, BC from breast cancer programs, familial cancer clinics, and population-based cohorts. Germline BRCA1or BRCA2mutations carriers were excluded. Eligible women had (1) LBC before age 45 or (2) LBC at any age with at least two 1st or 2nd degree relatives with BC of any type. Denaturing high pressure liquid chromatography was undertaken, followed by direct sequencing of exons displaying changes. Results: At the time of submission 310 of 383 samples have been fully sequenced. One previously characterized missense mutation and four novel non-synonymous variants (1.6%) were found. Three of these women had LBC before 45 years and no family history of BC; two had BC family history. No gastric cancers were reported in these families. Functional assays to assess the pathogenicity of the variants are in process. Conclusions: These results confirm that CDH1 is responsible for a small proportion of familial and early onset LBC. Given the difficulty of identifying CDH1 mutations from BC history alone and the importance of managing the gastric cancer risk in CDH1carriers, these findings should underscore the need to obtain an accurate abdominal cancer family history from women with LBC. No significant financial relationships to disclose.
Intermittent Dosage in the Treatment of Pulmonary Tuberculosis with Streptomycin
Authors: J. R. Bignall, J. W. Clegg, J. W. Crofton, B. J. Douglas, H. D. Holt, D. A. Mitchison, P. Armitage
Journal: BMJ (1950)

The emergence of drug-resistant tubercle bacilli has been the major difficulty in the streptomycin treatment of pul- monary tuberculosis.In the first Medical Research Council series of cases of pulmonary tuberculosis treated in this country (Medical Research Council, 1 948a) strains showing a streptomycin resistance more than 10 times that of the control were isolated from 35 out of 41 cases.The resistant organisms were usually first found within two months of beginning treatment, occasionally later.Towards the end of 1947, when the first trial was finishing, it was already obvious that any way of avoiding or delaying the emergence of resistance would be a major advance.The quantitative' studies of Pyle (1947) had shown that in pulmonary tuberculosis a minute proportion of strepto- mycin-resistant tubercle bacilli could be isolated from large inocula of the apparently sensitive pre-treatment strain.As streptomycin treatment continued and the sensitive organ- isms were gradually eliminated, the resistant minority came to occupy a larger and larger proportion of the bacterial population.E%7entually the proportion was sufficient to manifest streptomycin resistance in the comparatively crude routine tests.It seemed, therefore, that even in the absence of streptomycin there was a steady but very low mutation rate to streptomycin-resistant forms.In spite of this steady mutation the proportion of resistant forms did not seem to increase unless they were put at an advantage by exposure to the drug.This failure to increase suggested that in the absence of streptomycin the resistant bacilli might be at a disadvantage, and might therefore tend to die out during intermissions in treatment.It was known, of course, that once resistant forms were demonstrable in the crude tests it was unusual, in the indivi- dual case, to get reversion to sensitive strains.But it was unlikely that a single injection of streptomycin would eventually result in an entirely resistant bacterial population.Somewhere between these extremes the process might be reversible.It appeared possible, therefore, that by a
OSI-774 in advanced esophageal cancer: a phase II study
Authors: D. Radovich, D. Kelsen, M. Shah, D. Klimstra, S. G. Gavin, D. Munoz, D. H. Ilson
Journal: Journal of Clinical Oncology (2004)

4077 Background: Chemotherapy for advanced Esophageal Cancer (EC) has a response rate of 30–50% and there is no standard second-line regimen. Many ECs over express Epidermal Growth Factor Receptor (EGFR). The EGFR tyrosine kinase is inhibited by oral agent OSI-774, which has shown clinical activity with minimal toxicity in a number of solid tumors. Methods: Patients with measurable disease, treated with up to one prior chemotherapy regimen for metastatic disease (EGFR over expressing or non-over expressing by immunohistochemistry), are eligible. OSI-774 is given orally at 150mg daily, in 4-week cycles. Twenty-three patients (19 males, 4 females), ages 53–77 (mean 63.5), have been tested for EGFR status; 14 were EGFR over expressors (60%); 19 were adenocarcinomas, 4 were squamous histology. Eight patients were not treated (4 had deterioration before therapy, 2 were ineligible, 2 withdrew consent). Of the 15 treated, 11 had adenocarcinoma, 4 had squamous cancers. Ten patients (67%) were EGFR over expressors; Karnofsky Performance Status ranged from 70–100 (mean 80). Results: One confirmed partial response (EGFR+, squamous tumor, female, mediastinal lymph node disease) was observed after 2 cycles. The majority of patients (53%) progressed after one cycle. Two patients (13%) progressed during their second cycle and 3 (20%) progressed during a third cycle. One (EGFR+) maintained stable disease until he progressed after a sixth cycle (7%). No Grade 4 toxicities were seen. Three patients developed Grade 3 hepatic toxicity (2 had elevated alkaline phosphatase, 1 had elevated bilirubin and AST). Two patients had Grade 3 dermatologic toxicity (pustular skin rash) which resolved with antibiotics and dose reduction of OSI-774 to 100mg daily. Conclusions: OSI-774 appears to have activity in advanced esophageal carcinoma, with 1 of 15 pts (EGFR+, squamous histology) demonstrating a partial response. Accrual continues to identify the response rate of single agent OSI-774 in advanced EC. This study is supported in part by NCI Grant # NO1-CM17105. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Syntholabo
Contraceptive steroids and breast cancer. (Letter)
Authors: Stoll Ba
Journal: BMJ (1978)

J.D. Spencer and others discussing this relationship (April 22 1978 p. 1024) report that the recurrence rate in 44 Stage 2 breast cancer patients who had taken contraceptive steroids during the year before mastectomy was significantly lower than in a matched control series.  Although the numbers and length of follow-up were limited the observations suggest that the growth of recurrence may have been temporarily inhibited in some cases as a result of the patient taking a combined pill of progestin and estrogen.  It is a pity that the authors failed to mention evidence of this which was reported over 10 years ago.  Soft-tissue manifestations of recurrent and advanced breast cancer in 42 women were treated with Lyndiol an oral contraceptive containing a synthetic progestin of the 19-nor-steroid group associated with the estrogen mestranol.  After the contraceptive dose of 1 tablet daily for 2 months or longer almost complete regression of soft-tissue tumor was noted in 4 of 21 cases;  with a dosage of 4-6 tablets daily it was noted in 5 of 21 other cases.  The response rate and its mean duration were found to be almost identical with those noted in a series of 72 similar cases treated by various progestins alone.  Inhibition of breast cancer growth by progestins is seen in both pre- and postmenopausal women but is favored by the presence of circulating estrogen.  In the series treated with contraceptive steroids the response rate was only 6% in elderly patients with an atrophic vaginal smear but it was 40% in younger patients with evidence of estrogenization in the smear.  The observation is particularly interesting because Huggins reported that a combination of low-dosage estradiol and high-dosage progesterone is capable of extinguishing the growth of the hormone-sensitive chemically induced mammary cancer in noncastrated female rats.  He emphasized that the relative dose of estrogen and progestin may be critical for success.(FULL TEXT)
Contraception for Sicklers
Authors: R P Perkins
Journal: New England Journal of Medicine (1971)

In 1967 stabilization of the red-cell membrane in sickle-cell anemia by steroidal treatment was announced.  Based on the results of medroxyprogesterone treatment of a 17-year-old Puerto Rican girl with sickle-cell anemia over a 1-year period it is suggested that medroxyprogesterone can be considered a safe and effective contraceptive for patients  having sickle-cell anemia.  Oral contraceptives containing estrogen might aggravate the sickle-cell condition.
Immune and clinical responses in melanoma patients vaccinated with dendritic cells loaded with killed allogeneic melanoma cells
Authors: A. K. Palucka, H. Ueno, J. Connolly, J. Banchereau, J. Fay
Journal: Journal of Clinical Oncology (2005)

2509 Background: We demonstrated that dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor-specific naïve CD8+T cells in vitro. This approach would overcome HLA restriction inherent to peptide vaccines and allow diversification of immune responses including priming of many clones of CD8+ and CD4+T cells. Methods: We now vaccinated 20 patients with metastatic melanoma with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line (8 vaccines on monthly basis). DCs were generated from monocytes by culturing with GM-CSF and Il-4 and activated by additional culture with TNF and CD40 ligand. KLH was used as a control antigen. Results: As of December 2004, fourteen out of 20 patients are alive. The range of overall survival is 2–22 months, and the range of event-free survival is 1–19 months. Median survival cannot be calculated as yet since 70% of patients are alive. Vaccination is: 1) safe (no autoimmunity); 2) led to the induction of melanoma-specific T cell immunity and, 3) in two patients, long lasting objective clinical responses (one CR and one PR). In this study we have demonstrated in an HLA-A*0201+ patient an induction of melanoma specific immunity thus suggesting cross-priming since the killed melanoma cells used to load the DC vaccine are HLA-A*0201 negative. Furthermore, we have demonstrated the expansion of melanoma-specific T cell immunity in HLA-A*0201 negative patients. Conclusions: The present results justify the design of larger follow up studies to assess the immunological and clinical response to DC vaccines in patients with cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Argos Therapeutics, ODC Therapy
Thymic Recovery After Allogeneic Hematopoietic Cell Transplantation with Nonmyeloablative Conditioning Might Be Limited to Patients Younger Than 60 Years of Age.
Authors: Emilie Castermans, Muriel Hannon, Remi Cheynier, Laurence Seidel, Stéphanie Humblet-Baron, Evelyne Willems, Stephanie Corbier, Andre Gothot, Vincent Geenen, Brenda M. Sandmaier, Rainer F Storb, Yves Beguin, Frederic Baron
Journal: Blood (2009)
Abstract 11790: Echocardiography is Able to Detect Morphological and Functional Changes of the Right Heart in Sport Scuba Divers
Authors: Radek Pudil, Lucie Horakova, Miroslav Rozloznik, Constantino Balestra
Journal: Circulation (2014)

Introduction: Scuba diving represents stressful event for cardiovascular system. Breathing with compressed air, hyperbaric environment and microbubbles formation are the main factors are the most influencing factors for pulmonary circulation. Hypothesis: The aim of the study was to evaluate the change in morphology and function of the right heart after scuba dive with compressed air. Methods: Ten healthy sport divers (2 woman, 8 men, average age 42.1 ± 4.1 yrs., 21-52yrs) performed one scuba dive with compressed air (the depth was 20 meters, bottom tine 20 minutes, one safety stop at 3 m, water temperature 15°C). Echocardiography was performed just before and immediately after the dive, and every 60 minutes after surfacing with the aim to evaluate the presence of microbubbles (iVivid, GE). Results: After the dive, left atrium, right ventricle and inferior vena cava diameters significantly decreased (LA: 30.4±2.1 vs. 27.1±1.2 mm, p&lt;0.05; RV: 27.8±2.1 vs. 25.2±1.1mm, p&lt;0.05; IVC: 19.3±1.1 vs. 17.6±0.9 mm, p&lt;0.05). LV ejection fraction, fractional shortening and myocardial performance index remained unchanged (LVEF: 65.7±7.1 vs. 62.2±10, p ns; FS: 40.9±6.1 vs.38.9±9.9, p ns; LV MPI: 0.50±0.15 vs. 0.48±0.14, p ns). We found significant decrease in mitral E/A (E/A 1.37±0.18 vs. 1.19±0.15 m/s, p&lt;0.05). Right ventricle functional parameters decreased (TAPSE: 29.9±2.1 vs. 26.1±2.2 mm, p&lt;0.05; RV MPI: 0.58±0.18 vs. 0.43±0.16mm, p&lt;0.05). Analysis of the pulsed tissue Doppler velocities of the tricuspid annulus showed significant decrease in S’ parameter (S’lat 16.1±1.1 vs. 13.9±2.3, p&lt;0.05). In 8 divers (80%), microbubbles were detected in right heart. They were detectable in pulmonary circulation for 3 hours. Due to this fact, the Doppler estimates of pulmonary artery pressure were not possible. Conclusions: Scuba dive with compressed air is associated with decrease of the both ventricle and atria diameters. It is associated with the decreased diastolic LV function and global RV function. These changes can be associated with the presence of microbubbles in lung circulation. This study showed echocardiography is able to detect changes of the circulation which are associated with the recreational dive.
Abstract 11313: Cardiac-Specific Overexpression of Catalase Attenuates Myocardial Hypertrophy and Diastolic Dysfunction in Diet-Induced Metabolic Syndrome in Mice
Authors: Fuzhong Qin, Vivian Tu, Deborah A Siwik, Robert M Weisbrod, Y. James Kang, Richard A Cohen, Wilson S Colucci
Journal: Circulation (2013)

Background: We showed that an “American” diet high in fat and sugar (HFHS) induces metabolic heart disease (MHD) characterized by left ventricular (LV) hypertrophy, fibrosis and diastolic dysfuncti...