tbuckley/cabot-search huggingface dataset:
Screening for mutations in BRCA2 BRC repeats and RAD51 in breast and ovarian cancer families
Authors: Katrin Rapakko, Katri Heikkinen, Sanna-Maria Karppinen, Robert Winqvist
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1318 

Approximately 5-10% of breast and ovarian cancer cases are due to an inherited susceptibility gene mutation, especially in BRCA1 and BRCA2 . These tumor suppressor genes explain most of the cases in families with a large number (4-5+) of early-onset cancers. However, in smaller and particularly in breast cancer only families the contribution of BRCA1/BRCA2 germline mutations is only approximately 10-20%. In 1-2% of the BRCA1/BRCA2 mutation-negative cancer families, the disease appears linked to germline mutations in other known cancer susceptibility genes such as TP53 , PTEN , AR and ATM , the predisposing gene still being unknown in all of the remaining cases. BRCA2 has a specific role in DNA repair, regulating the activity of RAD51, the human homolog of E. coli RecA. The interaction occurs through the conserved BRC repeat motifs of BRCA2 and the BRCA2-RAD51 complex is crucial for homology-dependent recombinational repair of DNA double-strand breaks (DSBs) that occur frequently in dividing cells. Erroneous repair of these lesions can lead to cancer. As hereditary aberrations in BRCA2 BRC repeat motifs and RAD51 may connect to susceptibility to breast and ovarian cancer, we have analyzed 192 patients of 129 Northern Finnish cancer families for the occurrence of germline alterations, by using conformation sensitive gel electrophoresis (CSGE) and DNA sequencing. All alterations seen in the current study have been observed previously by others and have been classified either as unknown variants or polymorphisms. In order to investigate whether these mutations are disease-related or not, we have determined their frequencies in healthy controls (n = 288). Our results indicate that neither germline alterations in the BRC repeat region of BRCA2 nor changes in RAD51 contribute significantly to hereditary predisposition to breast or ovarian cancer, at least in the population studied here.
Combined Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR), an Active Frontline Regimen for High-Risk Patients with CLL.
Authors: William G. Wierda, S. O’Brien, A. Ferrajoli, S. Faderl, C. Koller, Z. Estrov, G. Garcia-Manero, S. Verstovsek, M. Browning, S. Lerner, M. Keating
Journal: Blood (2007)
Even “Moderate” Dose Cyclophosphamide for Severe Aplastic Anemia Is Associated with Significant Toxicities and Does Not Prevent Relapse and Clonal Evolution
Authors: Phillip Scheinberg, Danielle M. Townsley, Bogdan Dumitriu, Olga Rios, Barbara Weinstein, Minoo Battiwalla, Richard Childs, Cynthia E. Dunbar, A. John Barrett, Colin O. Wu, Neal S. Young
Journal: Blood (2012)
Breast Cancer Risk After Ovarian Stimulation for In Vitro Fertilization
Authors: Federica Tomao, Anselmo Papa, Silverio Tomao
Journal: JAMA (2016)

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Coronary Artery Complication in Kawasaki Disease and the Importance of Early Intervention
Authors: Shaojie Chen, Ying Dong, Marcio Galindo Kiuchi, Jiazhi Wang, Ruotian Li, Zhiyu Ling, Tingquan Zhou, Zhenglong Wang, Martin Martinek, Helmut Pürerfellner, Shaowen Liu, Mitchell W. Krucoff
Journal: JAMA Pediatrics (2016)

The timing and selection of patients with Kawasaki disease for corticosteroid use to prevent coronary artery complications remain controversial.To evaluate the effect of corticosteroid therapy in KD.Databases of Medline, The Cochrane Library, and the Clinicaltrials.gov website until July 2015. We used the key words ["Kawasaki disease"] and ["steroid" OR "corticosteroid"] to retrieve potentially relevant studies in the databases of Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2015. Both English and non-English literature was identified. Titles and abstracts were reviewed by 2 authors (S.C. and Y.D.) to determine suitability for inclusion. Relevant articles were reassessed by reviewing the full text. Discrepancies in study inclusion were resolved by consensus (M.G.K.).Clinical studies that compared corticosteroids plus intravenous immunoglobulin (IVIG) therapy with IVIG therapy alone in treating patients with KD. Studies either using corticosteroids as initial therapy or as rescue therapy were included.Investigators independently extracted the data information. Data were quantitatively synthesized using random-effects analysis.Rate of coronary artery abnormalities.Sixteen comparative studies characterizing 2746 patients were analyzed. The duration of illness before corticosteroids therapy was significantly shorter in the initial corticosteroids subset than in the rescue corticosteroids subset. The rate of coronary artery abnormalities was significantly lower in adjunctive corticosteroids therapy than in IVIG therapy (odds ratio [OR], 0.424; 95% CI, 0.270-0.665). Meta-regression based on known variables demonstrated that the overall efficacy was negatively correlated with the duration of illness before corticosteroid therapy (P < .001). Subgroup analysis, including studies using corticosteroids plus IVIG as initial therapy, showed a more advantageous effect than IVIG alone regarding coronary artery abnormality prevention (OR, 0.320; 95% CI, 0.183-0.560), whereas this benefit was not found in a subgroup of studies using corticosteroids as rescue therapy. Further analysis found that patients predicted at baseline to be at high risk of IVIG resistance seemed to obtain the greatest benefit from adjunctive corticosteroid therapy regarding coronary artery abnormality prevention (OR, 0.240; 95% CI, 0.123-0.467). The fever duration was significantly reduced in the corticosteroids group. The favorable effects of corticosteroids were conferred without an increased risk of adverse events.This study highlights the importance of timing to prevent coronary artery complication in treating KD. High-risk patients with KD benefit greatly from a timely and potent adjunctive corticosteroid therapy strategy.
Extramedullary Relapse of Multiple Myeloma - Plasma Cells Characteristics.
Authors: Ludek Pour, Sabina Sevcikova, Lucie Rihova, Lenka Kubiczkova, Henrietta Greslikova, Renata Kupska, Fedor Kryukov, Elena Dementyeva, Aneta Mikulasova, Lenka Zahradova, Zdenek Adam, Roman Hajek
Journal: Blood (2012)
Adding oral talactoferrin to first-line NSCLC chemotherapy safely enhanced efficacy in a randomized trial
Authors: Y. Wang, D. Raghunadharao, G. Raman, D. Doval, S. Advani, P. Julka, P. Parikh, S. Patil, S. Nag, J. Madhavan, A. Varadhachary
Journal: Journal of Clinical Oncology (2006)

7095 Background: Talactoferrin alfa (TLF) is an oral immunomodulatory protein with a novel mechanism. TLF showed preclinical anti-cancer activity alone and in combination with chemotherapy. In Phase I/II trials, TLF was safe with apparent single-agent anti-cancer activity in non-small cell lung cancer (NSCLC). Methods: 110 chemo-naive patients with advanced or metastatic NSCLC were randomized (1:1) in a multi-center trial to carboplatin/paclitaxel (C/P) therapy plus either TLF or placebo. Starting the day after C/P (C:AUC 5 mg/mL/min; P:175 mg/m 2 ) in chemo-cycles 1, 3 and 5, oral TLF (1.5 g BID) or placebo was administered in 35-day cycles for up to three cycles or until progression. Primary endpoint was Confirmed Response Rate (RR; PR+CR) by CT using RECIST. Secondary endpoints included Progression Free Survival (PFS) and Overall Survival (OS). Results: Baseline patient and disease characteristics were comparable in both groups. All 110 patients were included in the Intent To Treat (ITT) population. 100 patients with at least one CT scan after starting treatment were prospectively defined as the Evaluable population. Adding oral TLF to C/P enhanced efficacy on all endpoints examined including RR, PFS and OS. Confirmed RR in the 100 evaluable patients significantly increased from 29% to 47% (P = 0.05). Confirmed RR in the 110 ITT patients improved from 27% to 42% (P = 0.08). Median PFS in both evaluable and ITT patients improved by 2.8 months (67%). Median OS improved by 31% and 18% in evaluable and ITT patients, respectively. A landmark analysis comparing survival in patients with and without a PR showed a significant difference (P &lt; 0.01), suggesting a strong association between RR and survival. TLF appeared to be very safe and well tolerated with no drug-related SAEs. Fewer AEs were observed in the TLF arm than in the placebo arm, 346 and 432 AEs, respectively (P = 0.0023). The number of Grade 3/4 AEs was also lower in the TLF arm, 60 versus 91 (P = 0.0144). Conclusions: Adding oral TLF to standard C/P chemotherapy in NSCLC was safe and increased efficacy in a randomized, multi-center, double-blind, placebo-controlled trial, with apparent improvements in RR, PFS and OS. Results with TLF compare favorably to other anti-cancer agents. Oral TLF will be further evaluated in a Phase III trial. [Table: see text]
GW26-e4774 β1-adrenoceptor autoantibodies increase susceptibility to ventricular arrhythmias by shortening effective refractory period and prolonging MAPD90-30 in guinea pigs
Authors: Haixia Huang, Yuhui Zhao, Ping Liu, Suli Zhang, Yunhui Du, Huijun Zhang, Ye Wu, Peng Wang, Xiao Li, Tingting Lv, Li Wang, Huirong Liu
Journal: Journal of the American College of Cardiology (2015)
Factor Xa: PAR-1 growth loop is blocked by low-molecular weight heparins—A new perioperative and adjuvant concept in glioblastoma.
Authors: Susanne Antje Kuhn, Tobias Kratzsch, Viktor Gruenwald, Hannes Haberl
Journal: Journal of Clinical Oncology (2013)

2038 Background: Glioblastoma patients suffer from thromboembolism, aggravating the disease. Recently, increased activity was shown for coagulation factors II, VIII, IX, X, XI, and XII in patient peripheral blood. In vitro, the high potential of FXa-PAR1-loop as growth factor system and significant effects of its blockade were proven. Methods: Patient samples (n=108) were analyzed for FXa and PAR-1. In immunodeficient mice, glioblastoma xenografts were established and treated with low-molecular weight heparins (LMWH) (30mg/kg SC daily for 3 wks). Phosphate buffered saline served as control. Tumor growth rates, final tumor size, tumor proliferation (Ki67), and tumor vascularization (CD31) were determined. Results: Human glioblastomas overexpressed FXa and PAR-1 in the compact tumor center (FXa: p&lt;.001; PAR-1: p&lt;.001) and in the invasion zone (FXa: p=.006; PAR-1: p=.005). Neoangiogenic endothelial cells disproportionately high expressed FXa and PAR-1 with rising intensity in the invasion zone (FXa: p&lt;.001; PAR-1: p&lt;.001), and the compact tumor mass. (FXa: p&lt;.001; PAR-1: p&lt;.001). Growth curves of LMWH-treated tumors slowed (p&lt;.001). Final tumor size was reduced (s.c.: p&lt;.001; i.c.: p&lt;.05). Tumor cell proliferation was massively inhibited in situ (tinzaparin: p&lt;.001; enoxaparin: p&lt;.001) as was the number of CD31 positive endothelial cells ((tinzaparin: p&lt;.001; enoxaparin: p&lt;.001) and the tumor vascularization (p&lt;.001 each). Conclusions: Glioblastoma patients display abnorm activation of coagulation factors in peripheral blood and show high levels of FXa and PAR-1 in the tumor center, invasion zone and angiogenic endothelia. LMWH caused tumor growth retardation and size reduction with blockade of proliferation and vascularization. FXa inhibition should be considered as continuous thrombosis prophylaxis and adjuvant glioblastoma treatment.
Vinorelbine plus capecitabine in salvage therapy of breast cancer. Comparison of intravenous vs oral administration of vinorelbine
Authors: V. Lorusso, R. Forcignanò, S. Leo, M. Ciccarese, V. Chiuri, G. Santacroce, G. Romano, S. Romano, C. Manca
Journal: Journal of Clinical Oncology (2008)

1114 Background: Capecitabine (C) and vinorelbine (V) have shown activity in advanced breast cancer (ABC). Two subsequent phase II trial were conducted in order to evaluate the response rate (RR) and time to progression (TTP) of CV combination in patients (pts) with ABC progressing after first line anthracycline plus/minus taxane based chemotherapy. Due to the supposed equiactivity of iv and oral (po)formulation of V, the only difference of the two trials was the route of administration of V. Methods: Seventy-six pts affected by ABC were included (38 in each study, respectively) and treated with the combination of C 2,000 mg/m2 (from 1st to 14th day) plus V 25 mg/m2/iv or 60 mg/m2 /po (days 1st+8th) q3w. With regard to previous treatments for metastatic disease, 12 patients (15.8%) had received anthracyclines, 6 patients (7.9%) taxanes, and 58 patients (76.3%) both drugs, respectively. The pts characteristics were well balanced between the two pts groups. Results: In the iv V group, of 38 evaluable pts, 14 (36.9%) achieved PR, 9 (23.6%) SD, and 15 (39.5%) PD, (overall disease control: 60.5%). With a median follow-up of 24 months (range 6–40+), the median TTP was 6.8 months (range 1–20.5+) and median survival was 11.3 months (range 6–40+). In the po V group, out of 38 pts, we observed 2 (5.3%) CR, 13 (34%) PR, 14 (36.9%) SD, and 9 (23.6%) PD (overall disease control: 76,3%). The median TTP was 7 months (range 2–18 months), and the median survival was 10 months (range 2–26+). A total of 462 courses were given with a mean of 6 cycles per patient (range 1–20). Grade 3–4 neutropenia was observed in 4 pts (9.4%) in the iv group vs 8 pts (21.6%) in the po group, respectively (p<.05). Moreover, G2-G3 anemia in 5 pts (13.5%) and G3 thrombocytopenia in 1 pt (2.7%) were observed only in the po group. Grade 2–3 hand foot syndrome and G2 diarrhoea were observed in 2 pts (5.4%) and in 3 pts (8%) in each group, respectively. Conclusions: The combination of CV, with V administered either iv or po, had comparable activity with overall disease control of 60.5 vs 76.3%, respectively. Toxicity was also similar, although po V induced significant more neutropenia. In conclusion, the full oral combination of CV represents a good treatment alternative for pts with pretrated ABC. No significant financial relationships to disclose.
CHOP Chemotherapy Plus Campath-1H (CHOP-C) as First Line Treatment in Patients with Peripheral T-Cell Lymphoma (PTCL).
Authors: Andrea Gallamini, Francesco Zaja, Livio Gargantini, Annunziata Manna, Vincenzo Secondo, Alessandro Levis, Luigi Rigacci, Patrizio Mazza, Emilio Iannitto, Antonello Pinto, Alessandra Tucci, Caterina Patti, Valerio Zoli, PierFederico Torchio
Journal: Blood (2005)
The use of statins may prolong survival of non-small cell lung cancer patients
Authors: D. Wang, A. Hanbali, M. Jankowski, E. U. Duran, A. Syed, S. Farhan, R. Chapman
Journal: Journal of Clinical Oncology (2006)

7149 Background: Hypercholesterolemia is one of the most common morbidities in United States. Statins have been proven as effective cholesterol-lowering agents and have been widely used in this country. They have been reported reducing the incidence and risk of various cancer types. However, the impact of using statins on the survival of patients with diagnosed non-small cell lung cancer is unknown. Methods: Ongoing retrospective study involves a cohort of 1,233 patients with diagnosed non-small cell lung cancer. Patients were identified from the Tumor Registry at Henry Ford Health System between January 1999 and December 2004. To date, the electronic medical records from 407 of the 1,233 cases were reviewed. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Data from 407 patients were included in this analysis. There were 109 patients with hypercholesterolemia, 54 of them were statin users at the time of their non-small cell lung cancer diagnosis. Average age was 70 (range 46–85) years for statin users and 65 (range 29–93) years for non statin users. Median survival of 407 subjects was 9.82 months. After stratifying for statin use, the median survival of statin users was 12.38 months while the median survival of non statin users was 9.75 months, with a p value of 0.012. Conclusion: Though small sample size, this study is the first time ever suggesting a possible survival benefit of statin use in patients with non-small cell lung cancer who have received their standard anti-tumor regimens. Other variables that may contribute to this result will be further clarified and discussed after completing the data collection and analysis of this entire cohort. Based on our preliminary result, a prospective study of co-morbidity management with statins in patients with non-small cell lung cancer is warranted. No significant financial relationships to disclose.
Efficacy and safety of angiogenesis inhibitors in advanced gastric cancer: a systematic review and meta-analysis
Authors: Jing Yu, Yue Zhang, Lai-Han Leung, Lian Liu, Fan Yang, Xiaojun Yao
Journal: Journal of Hematology & Oncology (2016)

Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been investigated in several studies for the treatment of advanced gastric cancer (GC). In the present study, we aimed to evaluate the efficacy and safety of angiogenesis inhibitors in advanced GC. We searched published randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for the treatment of GC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched. The extracted data on progression-free survival (PFS) and overall survival (OS) were measured in terms of hazard ratios (HR) and corresponding 95 % confidence intervals (CIs). In addition, risk ratios (RR) and corresponding 95 % CIs were pooled for objective response rate (ORR), disease control rate (DCR), and risk of adverse events (AEs). Ten RCTs involving 2786 patients were included. Compared with non-angiogenesis inhibitor-containing regimens, angiogenesis inhibitor-containing regimens resulted in a significant improvement in OS (HR 0.80, 95 % CI 0.69–0.93, P = 0.004), prolonged PFS (HR 0.66, 95 % CI 0.51–0.86, P = 0.002), and superior ORR (RR 1.34, 95 % CI 1.09–1.65, P = 0.005) and DCR (RR 1.37, 95 % CI 1.17–1.61, P = 0.0001). Angiogenesis inhibitors were associated with a greater number of AEs, but most of these were predictable and manageable. However, hand-foot syndrome, diarrhea, and gastrointestinal (GI) perforation were significantly increased in patients treated with angiogenesis inhibitors. In summary, angiogenesis inhibitor-containing regimens were superior to non-angiogenesis inhibitor-containing regimens in terms of OS, PFS, RR, and DCR in patients with advanced GC.
Drug related deaths in England and Wales
Authors: John Middleton, Sara McGrail, Ken Stringer
Journal: BMJ (2016)

A public health and primary care emergency

Figures from the Office for National Statistics published last month show that total drug related deaths in England and Wales increased by 65.7% and opioid related deaths by 107% between 2012 and 2015.1 These figures exclude deaths from bloodborne viruses and other conditions related to use of illegal drugs, so the actual mortality associated with drug use will be higher. In a report published the same day, Public Health England2 suggests contributors to the increase in deaths, including the rising age and increased physical frailty of drug users, interactions with other drugs and new psychotropics, and variations in the street purity and availability of opiates. Over half of the drug related deaths were among people who used opiates and had had no recent contact with drug services.

Public Health England suggests local and national actions to counter this public health emergency, including use of its updated prescribing guidelines, more extensive availability of naloxone, and a new Public Health Outcomes Framework indicator for drug related deaths. The report is silent, however, on systemic factors that may have …
The Addition of Rituximab to Combination Chemotherapy with CHOP Has a Long Lasting Impact on Subsequent Treatment in Remission in Follicular Lymhoma but Not in Mantle Cell Lymphoma: Results of Two Prospective Randomized Studies of the German Low Grade Lymphoma Study Group (GLSG).
Authors: Wolfgang Hiddemann, Roswitha Forstpointner, Michael Kneba, Norbert Schmitz, Rudolf Schmits, Bernd Metzner, Marcel Reiser, Eva Lengfelder, Bernhard Woermann, Hariett Harder, Susanna Hegewisch-Becker, Wolfgang Berdel, Georg Hess, Hartmut Eimermacher, Ali Aldaoud, Manfred Planker, Reza Parwaresch, Martin Dreyling, Michael Unterhalt
Journal: Blood (2004)
Dose-dense (DD) two-weekly docetaxel/doxorubicin/cyclophosphamide (TAC) with G-CSF support compared to standard adjuvant TAC in breast cancer patients
Authors: S. Z. Latifzadeh, M. Salimi, M. Naghnaeian, V. Entezari
Journal: Journal of Clinical Oncology (2007)

11052 Background: TAC confers a significant disease free and overall survival benefits vs. FAC for patients with node positive breast cancer and prophylactic use of G-CSF is a reasonable supportive therapy to minimize myelosuppresive complications of this regimen. DD scheduling has shown improved clinical outcomes in breast cancer therapy. This study is trying to compare toxicities and tolerability of DD TAC with G-CSF support with TAC every 3 wks supported with G-CSF. Methods: Thirty seven patients were enrolled during the period 1/04 to 1/06. Cohort A (N=25) received six cycles of TAC (75/50/500 mg/m 2 every 3 wks) plus GCSF started on day 5 and Cohort B (N=12) received six cycles of TAC (75/50/500 mg/m 2 every 2 wks) plus GCSF started on day 2. All patients had normal cardiac, renal and liver function. Toxicities were evaluated by clinical assessment, CBC and liver function tests. Results: The incidence of febrile neutropenia was 15.8% and 16.7% in cohort A and B respectively (RR =1.06, 95% CI = 0.20–5.42). Grade III/IV anemia was detected in 5.3% of cohort A patients and 8.0 % of cohort B patients (RR=1.58, 95% CI=0.10–22.99). Ten percent of cohort A patients developed stomatitis grade III/IV while none of cohort B patients had this toxicity (RR=1.06, 95% CI = 0.94–1.17). Hospitalization due to chemotherapy complications (mainly neutropenia) in cohort A and B were 5.3% and 8.3% (RR =1.58, 95%CI = 0.10–22.99). Conclusions: DD two weekly TCA was reported to be feasible in patients with stage II - III breast cancer (Margolis et al. JCO, 2005). This study shows that DD TCA plus G-CSF has comparable toxicity profile with standard TCA regimen with shorter treatment period.
Primary Nasal NK/T Cell Lymphoma: Cytology and Level of the Antiapoptotic PI9 Protein Have Prognostic Relevance.
Authors: Céline Bossard, Karim Belhadj, Felix Reyes, Nadine Martin-Garcia, Alain Kümmer, Françoise Berger, Josette Brière, Anne-Catherine Baglin, Odile Casiraghi, Eric Lepage, Philippe Gaulard
Journal: Blood (2004)