tbuckley/cabot-search huggingface dataset:
Population-based prospective cohort study of psychosocial factors and survival of young Australian women with breast cancer
Authors: K. Phillips, R. H. Osborne, G. G. Giles, G. Dite, C. Apicella, J. L. Hopper, R. L. Milne
Journal: Journal of Clinical Oncology (2008)

9584 Background: A diagnosis of breast cancer is frequently associated with psychological distress and many women believe that their psychosocial response to their breast cancer diagnosis affects their prognosis. Studies of the issue have produced inconsistent results. Methods: A population-based sample of 708 Australian women diagnosed before age 60 years with non-metastatic breast cancer was followed up for a median of 8.2 years. Depression and anxiety, coping style and social support were assessed at a median of 11 months post-diagnosis using the Hospital Anxiety and Depression Scale, Mental Adjustment to Cancer scale, Courtauld Emotional Control Scale and the Duke-UNC Functional Social Support questionnaire. Hazard ratios (HR) for distant disease-free survival (DDFS) and overall survival (OS) associated with psychosocial factors were estimated separately using Cox proportional hazards survival models, with and without adjustment for known prognostic factors. Results: Distant recurrence occurred in 209 of 638 (33%) assessable patients and 170 of 708 (24%) patients died during the follow up period. There were no statistically significant associations between any of the measured psychosocial factors and DDFS or OS in the adjusted analyses. In unadjusted analyses, associations between greater anxious preoccupation and poorer DDFS and OS were observed (p=0.02). These associations were no longer evident after adjustment for established prognostic factors; greater anxious preoccupation was associated with younger age at diagnosis (p=0.03), higher tumor grade (p=0.02) and greater number of involved axillary nodes (p=0.008). Conclusions: The findings demonstrate that womens’ psychological responses to breast cancer are unlikely to have substantial effects on survival. Interventions for adverse psychosocial factors are warranted to improve quality of life but should not be expected to improve survival. No significant financial relationships to disclose.
The differential efficacy of docetaxel according to NSCLC histology and therapeutic effect of EGFR-TKIs.
Authors: S. Miura, H. Murakami, T. Naito, A. Tsuya, Y. Nakamura, K. Kaira, T. Takahashi, M. Endo, Y. Onozawa, N. Yamamoto
Journal: Journal of Clinical Oncology (2010)

e18050 Background: Morphology and EGFR mutation status are important biomarkers for chemotherapy selection in NSCLC. Although docetaxel is key agent for NSCLC in second-line therapy, the efficacy of docetaxel according to these biomarkers remains unclear. Methods: To assess the clinical efficacy of docetaxel for NSCLC in second-line therapy according to NSCLC histology and therapeutic effect of EGFR-TKIs, we retrospectively reviewed 454 NSCLC patients treated with docetaxel at Shizuoka Cancer Center between April 2002 and April 2009. Results: A total of 242 patients with advanced NSCLC treated with docetaxel as second-line therapy after failure of platinum- based chemotherapy were analyzed in this study. Sixty-one (25%) patients were squamous cell carcinoma (Sq) and 181 (75%) were non-squamous cell carcinoma (non-Sq). Patient characteristics (Sq/non-Sq) were as follows: median age (range) 64 (47-77)/63 (23-82); female 13/22%; non-smoker 11/16%; PS0-1 80/89%; stage IV 89/85%. Overall response rates (ORRs) were 1.6% for Sq group and 11.0% for non-Sq group (p = 0.02). Median progression free survival (PFS) was 1.6 months for Sq group and 1.9 months for non-Sq group (p = 0.03). In multivariate analysis, histological subtypes had an independent influence on PFS. After failure of docetaxel, 91 non-Sq patients were treated with EGFR-TKIs. Twenty-seven out of 91 patients had partial response (R: responder), and 64 did not response to EGFR-TKIs (NR: non-responder). ORR and median PFS of second-line docetaxel therapy in non-Sq (R) group were significantly superior to those in non-Sq (NR) group (ORR: 29.6 vs. 7.8%, median PFS: 5.3 vs. 1.8 months, respectively; p < 0.01). Conclusions: This retrospective study suggests that non-Sq histology and favorable therapeutic effect of EGFR-TKIs were useful predictive factors of docetaxel for NSCLC in second-line therapy. No significant financial relationships to disclose.
Variation among mouse ribosomal RNA genes within and between chromosomes.
Authors: T Sasaki, T Okazaki, M Muramatsu, R Kominami
Journal: Molecular Biology and Evolution (1987)

We compared nucleotide sequences of the transcription-initiation region of five mouse ribosomal DNA (rDNA) clones. Two clones were isolated from Japanese wild mice, Mus musculus molossinus, and the other three from BALB/c mice originating in M. m. domesticus. Two BALB/c clones that are derived from the same chromosome are very similar, suggesting the occurrence of intrachromosomal homogenization of rDNA repeats. However, the other clone of BALB/c was approximately as different from the former two clones as from the rDNA clones of M. m. molossinus. These results suggest that, compared with intrachromosomal homogenization, homogenization among rDNA repeats on nonhomologous chromosomes occurs relatively infrequently after the mouse subspecies separation.
Altered metabolism of cyclophosphamide given in a low-dose metronomic manner does not account for eventual resistance
Authors: U. Emmenegger, Y. Shaked, G. Bocci, I. Spasojevic, S. M. Ludeman, S. Man, R. S. Kerbel
Journal: Journal of Clinical Oncology (2005)

3185 Background: Low-dose metronomic chemotherapy (LDM), in particular regimens applying cyclophosphamide (CTX), has shown promising activity in preclinical and several phase I-II human studies comprising various tumor types. LDM is thought to act mainly via anti-angiogenic mechanisms (Nat Rev Cancer. 2004;4:423–36), and as such should be less prone to the rapid development of acquired resistance. However, in most instances tumors eventually relapse. Results obtained with PC-3 human prostate xenografts treated with daily oral LDM CTX suggest host-related resistance mechanisms that become functional after about 6 weeks of treatment. We hypothesized that modified CTX metabolism might contribute to this phenomenon. Methods: C57Bl/6J were treated with daily oral LDM CTX without breaks (Cancer Res. 2002;62:2731–5), and 4-hydroxy-CTX (4-OH-CTX) levels determined by mass spectrometry. Matrigel plug perfusion and tumor growth assays (PC-3 xenografts) were performed on mice ± pretreated for 8 weeks with LDM CTX. Cytochrome P450 3A4 activity was assessed in liver specimens obtained from mice under LDM CTX for 12 weeks. Results: 4-OH-CTX steady-state levels are in the 0.1 μg/ml range, which is above the IC50 obtained for endothelial cell proliferation in vitro (Cancer Res. 2002;62:6938–43). These levels are maintained over a period of at least 8 weeks. Pretreatement does not compromise the anti-angiogenic (Matrigel plug perfusion assay) or anti-tumor effects of LDM CTX. No induction of cytochrome P450 3A4 activity in liver microsomes was observed. Conclusions: Oral LDM CTX results in steady-state plasma levels of 4OH-CTX which have been shown previously to exert relevant anti-angiogenic activity in vitro. Our results suggest that altered metabolism of CTX does not account for the emergence of the resistance seen (pre)clinically. In contrast to maximum tolerated dose regimens, cytochrome P450 3A4 activity is not induced by LDM CTX. The latter is important since potential combination partners of LDM CTX and many drugs used in cancer care are metabolized by cytochrome P450 3A4. No significant financial relationships to disclose.
Reoperation for Margins After Breast Conservation Surgery
Authors: Uttara Nag, E. Shelley Hwang
Journal: JAMA Surgery (2016)

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Cardiac toxicity in a phase II study of doxorubicin (DOX) and bevacizumab (BEV) for patients (pts) with metastatic soft-tissue sarcomas (STS)
Authors: D. R. D'Adamo, S. Anderson, K. Albritton, J. Yamada, E. Riedel, K. Scheu, G. K. Schwartz, H. Chen, R. G. Maki
Journal: Journal of Clinical Oncology (2004)

9012 Background:BEV (Avastin®) is an anti-VEGF monoclonal antibody with activity in colon, breast, and renal cell carcinomas. Since STS are largely resistant to standard chemotherapy, we hoped to determine response rate (RR), toxicity, time to progression, and survival of pts with STS treated with BEV and DOX. Methods: Pts could have had up to 1 non-anthracycline line of therapy. DOX was given at 75mg/m2 IV push followed by BEV IV 15mg/kg q3wk. Dexrazoxane (DEXR) was started for total DOX dose > 300 mg/m2. Pts were restaged every 2 cycles. Results: From 12/02 to 12/03 17 pts were enrolled: 13 F, 4 M; median age 54 (range 39–71); ECOG PS median 0 (range 0–2); prior therapy: surgery 12, radiation 2, chemotherapy 6. 11 pts had leiomyosarcoma. 82 cycles of BEV/DOX have been administered, median 4, range 1–12. 13 pts are evaluable. Five remain on study. Two partial responses (14%) were seen for 7 and 12 cycles. Ten pts (59%) had stable disease ≥ 4 cycles (SD). Four pts developed cardiac toxicity (EF<50%), three grade G2 (DOX 300, 300, 420 mg/m2) and one G3 (DOX 591 mg/m2). There were 2 episodes of neutropenic fever. Other G3–4 toxicities were neutropenia (24%), stomatitis (12%), and asthenia (12%). One pt with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment related. There was no hypertension or proteinuria over G1, and no thromboembolic events. One pt with LMS had G2 vaginal bleeding in the setting of progression. Conclusions: Although the RR (14%) is in line with other studies of single agent DOX, the SD > 4 cycles seen with the combination warrants further study in STS. The observed cardiac toxicity, despite close monitoring and DEXR, obliges a change in the dose and schedule of DOX and/or DEXR in future studies of this combination. No significant financial relationships to disclose.
The Mode of Delivery and the Risk of Vertical Transmission of Human Immunodeficiency Virus Type 1 — A Meta-Analysis of 15 Prospective Cohort Studies
Authors: The International Perinatal HIV Group
Journal: New England Journal of Medicine (1999)

To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies.
The Coalition of cancer cooperative groups GI scientific leadership council
Authors: R. B. Catalano, R. L. Comis, M. J. O’Connell
Journal: Journal of Clinical Oncology (2006)

13522 Background: The Coalition of Cancer Cooperative Groups convened the GI Scientific Leadership Council (GI SLC) to provide leadership in establishing and advancing national research priorities for colorectal cancer clinical trials. A key objective was to complement and enhance the scientific programs of the NCI-sponsored GI Intergroup. Methods: A multidisciplinary group of investigators representing the spectrum of diagnostic, therapeutic, and laboratory disciplines engaged in colorectal cancer clinical research was convened in December 2004 to address the most important research opportunities in colorectal cancer, and clinical trials to address those opportunities. In April 2005, the concepts evolved were discussed with representatives of the patient advocate community and the pharmaceutical industry. In December 2005 the GI SLC presented its core research recommendations to more than 100 members of the cancer community. Results: Seven principal cross-cutting themes emerged, as well as ten strategic recommendations to be addressed over the next three years. A portfolio of high priority clinical trials was identified. The GI SLC has prioritized support for three colon cancer surgical adjuvant trials; two rectal cancer surgical adjuvant trials; two colorectal cancer metastatic to the liver trials; two metastatic colorectal trials; and one colon polyp and cancer detection study trial. These will be detailed in our presentation. Conclusions:The GI Scientific Leadership Council represents a novel approach to strengthen colorectal cancer clinical trials and correlative science research in the United States by providing a platform to bring together clinical investigators and translational researchers, the patient advocate community, and the pharmaceutical industry. The GI SLC plans to convene a Cancer Prevention Advisory Group in the first quarter of 2006 and plans to initiate one or more innovative clinical trials in collaboration with industry in 2006. The GI SLC will meet throughout 2006 to develop action plans, review progress towards those plans, and facilitate adoption of the research priorities across the cancer community. No significant financial relationships to disclose.
Feasibility of thermal infrared imaging screening for breast cancer in rural communities of Southern Mexico: The experience of the Centro de Estudios y Prevencion del Cancer (CEPREC)
Authors: F. Gutierrez-Delgado, J. Vazquez-Luna, L. Venegas-Hernandez, S. Terrazas-Espitia, S. Marcial-Toledo, C. Guzman-Patraca, J. Perez-Romero, M. Saldana-Tellez
Journal: Journal of Clinical Oncology (2009)

1521 Background: Breast cancer is the second cause of death from cancer among Mexican women but the incidence continues to rise mainly in rural communities. However, among women older than 50 years, only 7% of them report having had a mammogram because of insufficient number of mammography equipment and trained health care professionals. Mammography has limitation in sensitivity and specificity greater than 70 % and greater than 80 %, respectively. Breast thermography is a noncontact, noninvasive technique and easy to use outside hospitals. We propose to evaluate the feasibility of thermal infrared imaging as screening tool for early detection of breast cancer. Methods: Between November 2006 and December 2008, women were offered clinical breast examination (CBE) followed by breast thermography and mammography, and biopsy if indicated. Thermal infrared imaging was obtained by using an infrared camera (DL-700; 320*240 UFPA, Zhejiang Dali Technology Co., Ltd.). Infrared imaging was performed in a controlled environment with temperature and humidity maintained between 18 ºC and 23 ºC. Breast thermography diagnosis was established according to Hobbins criteria where TH1 to TH5 are equivalent to BI-RADS I to V (Intermer J of Rad 1987;12:337). CBE and breast thermography were correlated with mammography and histologic diagnosis. Results: Nine hundred and eleven (100%) women (median age 44 years, range 15–83) were evaluated. Five hundred and three (55%) of them were older than 40 years, 137 (15%) were between 35 and 39 years. Cancer was diagnosed in 14 (3%) and 2 (1.4%) women, respectively. Overall cancer was diagnosed in 16 (2.5 %) out of 640 women older 35 years. Among 116 (13%) women between 30 and 34 years, cancer was found in 1 (0.8 %) patient. Cancer was not found among 155 (17%) women between 15 and 29 years. Conclusions: In this study cancer was diagnosed in 1.8 % of women by using breast thermography. Thermal infrared imaging allows to select patients who could require further work-up. Breast thermography emerges as a potential screening tool for early detection of breast cancer. No significant financial relationships to disclose.
Junior doctor is suspended for citing colleagues on falsified research without their knowledge
Authors: Clare Dyer
Journal: BMJ (2016)

A junior doctor who cited her senior colleagues without their knowledge as coauthors in papers that were later retracted for faulty or fabricated data has been suspended for 12 months by the Medical Practitioners Tribunal Service in Manchester.

Gemina Doolub was working in cardiology for Oxford University Hospitals NHS Trust in 2013 when she submitted a research paper to ISRN Cardiology 1 and a research abstract to the Journal of the American College of Cardiology .2

In the research paper, submitted in or around February 2013, she cited Erica Dall’Armellina, a clinical research fellow at the John Radcliffe Hospital, as a coauthor, fabricating an email address for her. Neither Dall’Armellina nor …
Enhancement of the Antitumor Effect of 1,3-Bis(2-Chloroethyl)- 1-Nitrosourea by Chlorpromazine and Caffeine2
Authors: Martin H. Cohen
Journal: JNCI Journal of the National Cancer Institute (1973)

Murine L1210 leukemia, combined with chlorpromazine, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and caffeine, markedly increased survival of mice over treatment with BCNU alone. All 3 drugs had to be given together, because neither chlorpromazine plus BCNU nor BCNU plus caffeine treatment improved survival relative to an appropriate control group. The optimal time for chlorpromazine treatment was 6 hours before BCNU. Prior exposure to caffeine of both recipient mice and L1210 cells used for transplantation did not affect therapeutic response. The mechanism of enhancement of BCNU by chlorpromazine and caffeine is unknown.
Maintenance rituximab versus observation after R-CHOP or R-EPOCH in patients with untreated poor-prognosis diffuse large B-cell lymphoma and grade III follicular lymphoma.
Authors: Y. J. Li, Z. J. Xia, S. Li, X. Q. Chen, Y. Xia, F. Xu, Z. H. Wang
Journal: Journal of Clinical Oncology (2010)

8084 Background: The prognosis of diffuse large-B-cell lymphoma (DLBCL) with poor risk (International Prognostic Index, IPI=3-5 or bulky disease) is poor. A considerable proportion of patients with poor-risk relapsed after rituximab in combination with CHOP or CHOP-like chemotherapy. It has been widely demonstrated that maintenance rituximab (MR) can improve survival rate in follicular lymphoma (FL), but it's unclear in DLBCL. The objective of this study is to investigate the efficacy and safety of maintenance rituximab therapy in DLBCL patients with poor risk. Methods: 50 untreated DLBCL patients (including 6 FL III) with poor risk (IPI=3-5 or bulky disease) who achieve complete remission (CR) or complete remission unconfirmed (CRu) after 6∼8 cycles of R-CHOP or R-EPOCH (±invasion field radiotherapy) were enrolled. They were assigned to MR (n=21) for two years or till to relapse or death or observation only (OBS) (n=29). Results: Two-year disease-free survival (DFS) and overall survival (OS) rates for MR were 93.3% and 93.8%, respectively. 2-year DFS and OS rates for OBS were 69.4% and 87.7%, respectively. DFS was significantly prolonged (p=0.046), but no significant difference in OS was seen (p=0.519). Median DFS and OS of both arms were not reached. The main toxicities of MR were grade I-II hematological toxicity. Grade III-IV toxicities were rare (3.9%). Conclusions: Our results suggest that maintenance rituximab for two years significantly prolonged DFS but not OS in untreated DLBCL patients with poor risk. The toxicities were few and mild. No significant financial relationships to disclose.
Weekly docetaxel and bortezomib in the treatment of patients with advanced hormone refractory prostate cancer (HRPC): A Minnie Pearl Cancer Research Network phase II trial
Authors: A. A. Meluch, D. S. Spigel, F. A. Greco, J. H. Barton, G. Messina, B. Gould, M. A. Rovito, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2005)

4735 Background: Docetaxel (75mg/m2 every 3 weeks) is now standard first-line treatment for patients (pts) with HRPC. Bortezomib, a novel proteosome inhibitor, has shown single-agent activity in pts with refractory HRPC. In an effort to improve efficacy of treatment, we evaluated the combination of docetaxel and bortezomib in this multicenter, community-based phase II trial. Methods: Eligibility criteria: metastatic HRPC; no previous chemotherapy; ECOG PS 0–2; measurable metastatic disease or rising PSA levels with osseous metastasis; serum creatinine ≤ 2mg/dl; adequate hepatic and bone marrow function; informed consent. All patients received docetaxel 30mg/m2 IV and bortezomib 1.6mg/m2 IV both given on days 1, 8, 15 of each 28-day cycle. Bortezomib was administered 60 minutes after infusion of docetaxel. Pts were evaluated for response after 8 weeks of treatment; treatment continued in responding patients for 6 cycles. Results: 30 of a planned 50 pts enrolled between 7/03 and 10/04: median age, 70 years; > 1 hormonal therapy, 70%; ECOG 0/1/2, 37%/60%/3%; osseous metastases only, 57%; osseous/soft tissue, 37%; soft tissue only, 7%; prior prostatectomy, 53%; prior localized XRT, 43%. At present, 22 pts have been evaluated for PSA response: PR 5 (23%), stable 12 (54%), progression 5 (23%). 2 of 11 pts with measurable disease (18%) had PR. With median followup of 4 months, 73% of pts remain progression-free. Grade 3/4 toxicities included: fatigue 1 (3%); nausea 1 (3%). 2 pts had grade 2 neuropathy. There were no treatment-related hospitalizations. Conclusions: The regimen of docetaxel followed by bortezomib administered on a weekly basis has activity and acceptable toxicity in patients with metastatic HRPC. Updated efficacy results will be presented. No significant financial relationships to disclose.
Chromosome Studies on Normal and Leukemic Human Leukocytes
Authors: Peter C. Nowell, David A. Hungerford
Journal: JNCI Journal of the National Cancer Institute (1960)

Chromosome studies were made on myeloblasts obtained from the peripheral blood of 4 patients (3 males, 1 female) with acute or chronic granulocytic leukemia and on leukocytes from 3 healthy individuals (1 male, 2 females). The cells were grown in culture for 2 to 4 days before examination. Both in normal and in leukemic cells, the predominant metaphase chromosome number was 46. However, idiogram analyses revealed a definite abnormality, probably involving the Y chromosome, in the 2 cases of chronic granulocytic leukemia. No chromosome abnormality was distinguishable in the 2 cases of acute leukemia (1 male, 1 female) investigated. The results indicate that in some leukemic human leukocytes small but definite chromosomal changes are demonstrable.
Abstract 17079: CHA2DS2-vasc Score is More Sensitive in Predicting Thromboembolic Risk Than CHADS2 Score in Atrial Fibrillation
Authors: Mi Na Kim, Su-A Kim, Yong Hyun Kim, Jong Il Choi, Seong-Mi Park, Sang won Park, Young-Hoon Kim, Wan Joo Shim
Journal: Circulation (2012)

Background: CHADS2 score has been revised as CHA2DS2-VASc score for better thromboembolic risk stratification in patients with atrial fibrillation(AF). Impaired left atrial(LA) and left atrial appe...