tbuckley/cabot-search huggingface dataset:
Integrative Analysis of DCE-MRI and Gene Expression Profiles in Construction of a Gene Classifier for Assessment of Hypoxia-Related Risk of Chemoradiotherapy Failure in Cervical Cancer
Authors: Christina S. Fjeldbo, Cathinka H. Julin, Malin Lando, Malin F. Forsberg, Eva-Katrine Aarnes, Jan Alsner, Gunnar B. Kristensen, Eirik Malinen, Heidi Lyng
Journal: Clinical Cancer Research (2016)

A 31-gene expression signature reflected in dynamic contrast enhanced (DCE)-MR images and correlated with hypoxia-related aggressiveness in cervical cancer was identified in previous work. We here aimed to construct a dichotomous classifier with key signature genes and a predefined classification threshold that separated cervical cancer patients into a more and less hypoxic group with different outcome to chemoradiotherapy.A training cohort of 42 patients and two independent cohorts of 108 and 131 patients were included. Gene expression data were generated from tumor biopsies by two Illumina array generations (WG-6, HT-12). Technical transfer of the classifier to a reverse transcription quantitative PCR (RT-qPCR) platform was performed for 74 patients. The amplitude ABrix in the Brix pharmacokinetic model was extracted from DCE-MR images of 64 patients and used as an indicator of hypoxia.Classifier candidates were constructed by integrative analysis of ABrix and gene expression profiles in the training cohort and evaluated by a leave-one-out cross-validation approach. On the basis of their ability to separate patients correctly according to hypoxia status, a 6-gene classifier was identified. The classifier separated the patients into two groups with different progression-free survival probability. The robustness of the classifier was demonstrated by successful validation of hypoxia association and prognostic value across cohorts, array generations, and assay platforms. The prognostic value was independent of existing clinical markers, regardless of clinical endpoints.A robust DCE-MRI-associated gene classifier has been constructed that may be used to achieve an early indication of patients' risk of hypoxia-related chemoradiotherapy failure. Clin Cancer Res; 22(16); 4067-76. ©2016 AACR.
Analysis of Genome Alterations in Head and Neck Squamous Cell Carcinoma to Identify Potential Prognosis Biomarkers or Targetable Genetic Aberrations
Authors: B. Linot, O. Capitain, I. Valo, A. Septans, P. Augereau, A. Renoult, S. Fronteau, A. Morel
Journal: Annals of Oncology (2014)
Extra-Virgin Olive Oil Reduces Glycemic Response to a High–Glycemic Index Meal in Patients With Type 1 Diabetes: A Randomized Controlled Trial
Authors: Lutgarda Bozzetto, Antonio Alderisio, Marisa Giorgini, Francesca Barone, Angela Giacco, Gabriele Riccardi, Angela A. Rivellese, Giovanni Annuzzi
Journal: Diabetes Care (2016)

OBJECTIVE To evaluate whether fat quality, in the context of meals with high– (HGI) or low–glycemic index (LGI), influences postprandial blood glucose (PPG) response in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS According to a randomized crossover design, 13 patients with type 1 diabetes on insulin pump consumed two series (HGI or LGI) of meals with the same carbohydrate quantity while differing for amount and quality of fat: 1) low in fat (“low fat”), 2) high in saturated fat (butter), or 3) high in monounsaturated fat (extra-virgin olive oil) (EVOO). Premeal insulin doses were based on insulin–to–glycemic load ratios. Continuous glucose monitoring was performed and 6-h PPG evaluated. RESULTS PPG was significantly different between HGI and LGI meals (P = 0.005 for time × glycemic index interaction by repeated-measures analysis [RMA]), being significantly higher during the first 3 h after the HGI meals with a later tendency to an opposite pattern. In the context of HGI meals, PPG was significantly lower after EVOO than after low fat or butter (P &amp;lt; 0.0001 for time × meal interaction by RMA), with a marked difference in the 0- to 3-h glucose incremental area under the curve between EVOO (mean ± SD 198 ± 274 mmol/L × 180 min) and either low fat (416 ± 329) or butter (398 ± 355) (P &amp;lt; 0.05). No significant differences were observed in PPG between the three LGI meals. CONCLUSIONS Carbohydrate quality of a mixed meal influences shape and extent of PPG. Besides, using EVOO in a HGI meal attenuates the early postprandial glucose response observed when this meal is consumed with either low fat or butter. Therefore, an optimal prandial insulin administration would require considering, in addition to the quantity of carbohydrates, the quality of both carbohydrate and fat.
Abstract 18705: Simian Immunodeficiency Virus Induces Pulmonary Arterial Hypertension in Rhesus Macaques: A Hemodynamic Study
Authors: Jian Hu, Rebecca Tarantelli, Marc Simon, Timothy Bachman, Karen Norris, Hunter Champion
Journal: Circulation (2013)

Background: Our prior studies have shown that the Cyno Macaques and Resus Macaques infected with simian immunodeficiency virus (SIV) develop pulmonary arterial hyperplasia by histopathology. The hemodynamic changes with infection, however, remain unknown. The purpose of this study was to determine the relationship of the SIV infection and cardiac hemodynamic changes as assessed by invasive right heart catheterization. Methods: Five Rhesus macaques underwent pulmonary artery catheterization at baseline and 6 months after infection with SIV. Right atrial pressure (RAP), right ventricular end systolic pressure (RVESP), end diastolic pressure (RVEDP), and mean pulmonary artery pressure (mPAP) were measured directly using a pediatric pulmonary artery catheter. RV dp/dt min, dp/dt max, Tau and contractility index were calculated by Matlab software. In addition, mPAP was calculated in a larger cohort (n=24) by the regression formula: mPAP=RVSP*0.65+0.55 in order to validate this calculation in non-human primates. Results: After 6 months of SIV infection, RAP, RVSP, and mPAP increased significantly compared to baseline values. RVEDP trended toward being higher but was not statistically significant from baseline. The RV dp/dt min, dp/dt max and Tau didn’t show significant changes. The contractility index had a markedly decrease with SIV infection compared with baseline. Moreover, direct measure mPAP correlated well with the calculation of mPAP (R 2 =0.954; P&lt;0.0001). Conclusion: Based on the presented data we conclude that SIV induces pulmonary arterial hypertension in Rhesus monkeys concordant with the histopathological observation in our prior studies. SIV infection also decreases the RV contractility as well. These data suggest that this may be a viable large animal, preclinical model of PAH with hemodynamics and histology consistent with the human condition.
Phase II study of short-time infusion of oxaliplatin in combination with capecitabine (XELOX<sub>30</sub>) in patients with progressive colorectal cancer after irinotecan and 5-fluorouracil (FU) treatment
Authors: P. Pfeiffer, B. Glimelius, H. Sørbye, J. P. Mortensen, L. Baltesgard, K. M. Tveit, D. Ogreid, H. Starkhammar
Journal: Journal of Clinical Oncology (2004)

3562 Background: Oxaliplatin (Ox) in combination with FU or Capecitabine (Xel) prolong median survival as first and second line therapy in patients with advanced colorectal cancer (ACRC). Ox induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2 hour infusion is recommended, but in a prior pilot study (Pfeiffer et al, Acta Oncol 2003; 42: 832) a 30 minutes infusion could be given without additional neuropathy. Methods: For practical and economic reasons, but also for patient's convenience, we performed this phase II study to examine XELOX30 (Xel 1000 mg/m2 orally twice daily days 1–14 and Ox 130 mg/m2 as 30 minutes infusion day 1) in patients with progressive colorectal cancer after therapy with irinotecan and FU. Neuropathy was graded 0–3 using the Ox-specific scale. Other adverse events were graded using NCI-CTC. Results: From Nov 2002 to Sept 2003, 69 patients with ACRC were included and treated with XELOX30. Median age was 62 years (33–73), median WHO PS 1 (0–2). Median number of courses was 6 (range 1–10), median cumulative dose of Ox was 830 mg/m2. Response rate was 16%. Median TTP was 5.6 (4.6–7.5) months and median survival was 9.2 (8.6–12.6) months. Neurotoxicity: Grade 0: 9%, grade 1: 68%, grade 2: 17% and grade 3: 5%. Other grade 3 toxicities were nausea/vomiting: 7%, diarrhea: 8% and PPE 8%. Fourty patients have stopped therapy due to PD (n=20), GI-toxicity (n=7), neurotoxicity (n=2), patients wish (n=5) and other (n=6). Conclusions: XELOX30 is an active, and very convenient 2. line regimen with an excellent safety profile similar to other Ox schedules. No significant financial relationships to disclose.
Further Studies on the Relationship between the Genotype and the Mammary Tumor Agent in Mice
Authors: W E HESTON, M K DERINGER
Journal: JNCI Journal of the National Cancer Institute (1956)

This study investigates genetic control over the propagation and transmission of a mammary tumor agent.  Strain C3H female mice with a mammary tumor agent were outcrossed to strain C57BL males without the agent and genetically resistant to it.  The female offsprings were backcrossed to strain C57BL males through 7 successive backcross generations.  By the 3rd backcross generation the agent has been eliminated by concentration of strain C57BL chromatin; this suggests that strains differed by only a few genes controlling the propagation and transmission of the agent and possibly by only a single pair of genes.  Females of the 7th backcross generation were then outcrossed to C3Hf males (without the agent) and their female progeny backcrossed to C3Hf males through 4 backcross generations.  With the concentration of C3H chromatin the mammary tumor agent did not reappear suggesting that the concentration of C3H chromatin the mammary tumor agent did not reappear suggesting that the concentration of C57BL chromatin had eliminated the agent rather than causing it to mutate to a latent or inactive form.  Mammary tumors observed at an early age in females with the tumor agent were mainly adenocarcinomas of types A and B; some of the tumors occurred in older females with or without the agent.  Type C adenocarcinomas and adenoacanthomas were observed mostly in females of an advanced age both with and without the agent.  It is possible that this occurrence is associated with histologic changes of the mammary gland with advancing age rather than directly related to the agents absence.
Randomized phase III U.S./Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL).
Authors: P. J. Stiff, J. M. Unger, J. Cook, L. S. Constine, S. Couban, T. C. Shea, J. N. Winter, T. P. Miller, R. R. Tubbs, D. C. Marcellus, J. W. Friedberg, K. Barton, G. M. Mills, M. L. LeBlanc, L. Rimsa, S. J. Forman, R. I. Fisher
Journal: Journal of Clinical Oncology (2011)

8001 Background: This SWOG led intergroup trial investigated the benefit of autotransplant in 1st remission patients with bulky stage II, III, and IV H-Int/High IPI diffuse NHL after 5 cycles of CHOP±R, as previously suggested by European studies. Methods: 397 patients (pts) up to age 65 from 40 sites were enrolled between 9/97-12/07 and induced with 5 cycles of CHOP (n=215) or CHOP-R (after 3/03; n=182). Pts with ≥ PR were randomized between CHOP±R x 1 followed by autotransplant using TBI or BCNU based regimens, vs CHOP±R x 3. Primary endpoints were toxicity, and 2 yr PFS and OS for randomized pts with sample size chosen to detect a hazard ratio between arms 1.50 with 82% power. Results: Of 370 induction eligible pts 253 were randomized to standard (128) or transplant (125) therapies; 35% had High IPI . Reasons for non-randomization included progression (66), and refusal (23). On the transplant arm, 9 never received transplant and 6 had fatal toxicities (lung-3). On the standard arm, 3 did not receive CHOP±R and 3 had fatal toxicities. Forty-five transplant and 67 standard therapy pts have progressed or died: 2 yr PFS was 69 and 56% respectively [hazard ratio: 1.72 (95% CI: 1.18-2.51) p = .005]. Thirty-seven transplant and 47 standard therapy pts have died: 2 yr OS was 74 and 71% respectively [hazard ratio 1.24 (95% CI: 0.81-1.91) p = .32). Based on exploratory analyses, there was a significant differential treatment effect between the H-Int and High IPI pts for both PFS (interaction p value = 0.02) and OS (interaction p value = 0.01): for transplant vs standard arms, the 2 yr PFS was 66% vs 63% for the H-Int IPI pts and 75% vs. 41% for the High IPI pts; the 2 yr OS was 70% vs 75% for the H-Int IPI pts and 82% vs 64% for the high IPI pts. There was no differential treatment interaction by histology (B vs T) for either PFS (p=.43) or OS (p=.53), or for B-cell pts by induction (CHOP-R vs CHOP) for PFS (p=.35) or OS (p=.29). Conclusions: For advanced stage H-Int and High IPI diffuse aggressive NHL, early autotransplant improves PFS for responders, including those induced with CHOP-R, with a stronger outcome seen for those with High IPI grade.
Sorafenib in the treatment of Chinese patients with advanced renal cell cancer
Authors: Y. Sun, Y. Na, S. Yu, Y. Zhang, A. Zhou, N. Li, L. Yang, G. Lou
Journal: Journal of Clinical Oncology (2008)

16127 Background: A prior phase III trial (TARGETs) demonstrated that sorafenib doubled median progression-free survival versus placebo in previously treated clear cell renal cell cancer (RCC) patients (pts). The trial was conducted to explore the efficacy and safety profile of sorafenib in Chinese patients with advanced RCC. Methods: A total of 62 patients were enrolled for the open-label, non- randomized trial from April 20 to Dec. 28, 2006 in 4 hospitals in China. Major inclusion criteria: Histologically confirmed unresectable and/or metastatic RCC, at least one measurable lesion, failed one prior systemic therapy in the last 4 months, ECOG PS 0, 1 or 2, life expectancy more than 12 weeks, good organ function, no brain metastasis. Objectives were to evaluate the safety and efficacy of Sorafenib 400 mg bid continuously, 4 weeks per cycle. Tumor response was evaluated every 2 cycles. Results: A total of 62 patients were included in safety assessment. These patients were 69% were male with median age was 53yrs with most patients (85%) had prior nephrectomy, 77% with clear-cell histology. By August 20, 2007, the mean duration of treatment was 31 weeks, and 57 patients were eligible for response evaluation (RECIST criteria). One (1.75%) achieved CR, 11(17.5%, including one unconfirmed patient) had PR, 36 (52.6%, including six unconfirmed patients) had SD, and 9 (15.8%) were PD. The disease control rate (CR+PR+SD) was 73.5%. The median progression-free survival (PFS) was 41 weeks, and the median overall survival had not been reached with 278 days mean follow up time. 52 weeks survival rate is 73.6%. Grade 3 and 4 adverse events occurring in >2% pts were hand-foot skin reaction (16%), diarrhea (4.8%), and hypertension (3.2%). Conclusions: Sorafenib effectively controlled disease progression of advanced RCC with acceptable safety and tolerability. The disease control rate and toxicity profile in Chinese RCC patients are similar to that observed in the TARGET trial. No significant financial relationships to disclose.
Intensive chemotherapy with mitoxantrone and high-dose cytosine arabinoside followed by granulocyte-macrophage colony-stimulating factor in the treatment of patients with acute lymphocytic leukemia
Authors: HM Kantarjian, EH Estey, S O'Brien, E Anaissie, M Beran, MB Rios, MJ Keating, J Gutterman
Journal: Blood (1992)
Rates of Albumin and Transferrin Synthesis &lt;italic&gt;In Vitro&lt;/italic&gt; in Rat Hepatoma-Derived H&lt;sub&gt;4&lt;/sub&gt; II-EC&lt;sub&gt;3&lt;/sub&gt; Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S H Ohanian, S B Taubman, G J Thorbecke
Journal: JNCI Journal of the National Cancer Institute (1969)
Response to Letter Regarding Article, “Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans”
Authors: Csaba P. Kovesdy, Keith C. Norris, L. Ebony Boulware, Jun L. Lu, Jennie Z. Ma, Elani Streja, Miklos Z. Molnar, Kamyar Kalantar-Zadeh
Journal: Circulation (2016)
Abstract 329: Simvastatin Inhibits TGF-β1-induced Proliferation and Activation of Cardiac Fibroblasts Through Inhibition of SMAD Pathway
Authors: Farhan Rizvi, Ramail Siddiqui, Alesandra DeFranco, Akhil Jayaprakash, Mahek Mirza, Larisa Emelyanova, Gracious Ross, Ekhson Hulmohamedov, Daniel O’Hair, A. Jamil Tajik, Arshad Jahangir
Journal: Circulation Research (2014)

Background: HMG-CoA reductase inhibitors (statins) have been shown to reduce the incidence of atrial fibrillation (AF) and its progression but the underlying mechanisms are not fully elucidated. Since atrial fibrosis plays a major role in the development of the substrate for AF progression, we hypothesized that statins antagonize the effect of profibrotic cytokines, reducing their stimulatory effect on fibroblast proliferation, differentiation and activation. Methods: The effect of TGF-β1, a major profibrotic cytokine, on fibroblast proliferation and activation of myofibroblasts was assessed by expression of alpha smooth muscle actin (α-SMA) message (qPCR) and proteins (western and immunofluorocytochemistry) in the presence and absence of simvastatin (1-10μM). The inhibitory effect of simvastatin on SMAD 2/3 phosphorylation (western) and its nuclear translocation by TGF-β1 (5ng) was determined by immunofluorescence antibodies using fluorescent microscopy. Results: TGF-β1 treatment increased fibroblast proliferation (cell count) by 63% compared to control (p&lt;0.001) at 96 hours, which was inhibited by simvastatin by 61% (p&lt;0.001) (Fig a). Simvastatin also reduced TGF-β1-mediated myofibroblast differentiation (α-SMA positive) by 75% (p=0.02); (Fig b and c). TGF-β1 increased SMAD2/3 phosphorylation with increase in nuclear localization was inhibited by simvastatin. Conclusion: Simvastatin inhibits TGFβ-1-mediated cardiac fibroblast proliferation and myofibroblast differentiation by antagonizing SMAD phosphorylation and its translocation into the nucleus.
Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial
Authors: A. Roca, C. Oluwalana, A. Bojang, B. Camara, B. Kampmann, R. Bailey, A. Demba, C. Bottomley, U. D'Alessandro
Journal: Clinical Microbiology and Infection (2016)

Bacterial sepsis remains a leading cause of death among neonates with Staphylococcus aureus, group B streptococcus (GBS) and Streptococcus pneumoniae identified as the most common causative pathogens in Africa. Asymptomatic bacterial colonization is an intermediate step towards sepsis. We conducted a phase III, double-blind, placebo-controlled randomized trial to determine the impact of giving one oral dose of azithromycin to Gambian women in labour on the nasopharyngeal carriage of S. aureus, GBS or S. pneumoniae in the newborn at day 6 postpartum. Study participants were recruited in a health facility in western Gambia. They were followed for 8 weeks and samples were collected during the first 4 weeks. Between April 2013 and April 2014 we recruited 829 women who delivered 843 babies, including 13 stillbirths. Sixteen babies died during the follow-up period. No maternal deaths were observed. No serious adverse events related to the intervention were reported. According to the intent-to-treat analysis, prevalence of nasopharyngeal carriage of the bacteria of interest in the newborns at day 6 was lower in the intervention arm (28.3% versus 65.1% prevalence ratio 0.43; 95% CI 0.36-0.52, p <0.001). At the same time-point, prevalence of any bacteria in the mother was also lower in the azithromycin group (nasopharynx, 9.3% versus 40.0%, p <0.001; breast milk, 7.9% versus 21.6%, p <0.001; and the vaginal tract, 13.2% versus 24.2%, p <0.001). Differences between arms lasted for at least 4 weeks. Oral azithromycin given to women in labour decreased the carriage of bacteria of interest in mothers and newborns and may lower the risk of neonatal sepsis. Trial registrationClinicalTrials.gov Identifier NCT01800942.
State of Epstein-Barr Virus DNA in an American Burkitt's Lymphoma Line: Brief Communication 2
Authors: Steve Koliais, Gunnar Bjursell, Alice Adams, Tomas Lindahl, George Klein
Journal: JNCI Journal of the National Cancer Institute (1978)

A human lymphoma cell line, positive for the Epstein-Barr virus (EBV)-assoclated nuclear antigen, was recently established from a North American Burkitt's lymphoma. This cell line, SU-AmB-2, contained EBV DNA both in the form of circular, non-integrated DNA molecules of viral genome length, present in multiple copies per cell, and as integrated sequences. Having DNA present in both of these forms, it resembled cell lines established from African Burkitt's lymphomas. In studies on EBV strain differences, the episomal viral DNA in Burkitt's lymphoma cells may now be compared with viral DNA in nonmalignant cells with the use of cell lines from Burkitt's lymphoma patients of similar geographic origin.
Antitumor activity in a randomized phase II study comparing two schedules of NKTR-102 in patients (Pts) with pretreated metastatic breast cancer (MBC).
Authors: A. Awada, S. Chan, G. H. M. Jerusalem, R. E. Coleman, M. T. Huizing, A. Mehdi, S. M. O'Reilly, J. T. Hamm, P. J. Barrett-Lee, V. Cocquyt, K. Sideras, D. E. Young, M. Brown, C. Zhao, A. L. Hannah, L. K. Masuoka, A. Garcia, E. A. Perez
Journal: Journal of Clinical Oncology (2011)

1034 Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate with reduced peak concentration and a continuous concentration profile. Methods: This was an open-label phase II study in MBC pts following PD on a taxane; pts were randomized to NTKR-102 given IV at 145 mg/m2 over 90-min every 14 or 21 days. Primary endpoint: ORR by RECIST v1.0; secondary endpoints were safety and PFS. Each schedule followed a 2-stage Simon design (≥1 response in 15 pts in order to enroll an additional 20 pts per schedule). Results: 70 pts (35 per schedule) randomized from Feb09 − Apr10 (median follow-up: 8 mos). Median age: 55 (range 33-83). ECOG PS 0/1: 40%/60%. Neoadjuvant/adjuvant: 21% / 63%. Median number of prior cytotoxic regimens for metastatic disease (not including hormonal therapy/biologics): 2 (range 0−4). All pts had received prior taxane (T): 10% (adjuvant); 90% (metastatic). 87% had received prior anthracyclines (A): 59% (adjuvant); 29% (metastatic). 64% had received prior AT; an additional 23% had received prior AT/capecitabine (ATC). 61% were ER/PR+; 30% had TNBC; 87% had visceral metastases. Survival will be presented (>50% censored at present). Common related Grade 3/4 toxicity (q14d/q21d; n=70): diarrhea (20%/23%, median time to onset ~3 mon), neutropenia (11%/11%), fatigue (11%/9%) and dehydration (6%/9%). Withdrawal due to AEs: 20%/14% by schedule. Neuropathy was absent; alopecia was minimal (1% grade 2). Conclusions: NKTR-102 demonstrates significant anti-tumor activity in pts with advanced MBC, including pts with TNBC, visceral disease or prior ATC therapy. Toxicity was manageable. A phase III clinical trial is planned, with the schedule to be selected based on the full analysis of safety/activity data. q14d q21d Total ORR (n=31*/35) 32% 26% 29% CR 7% 0 3% PR 26% 26% 26% CR+PR+SD≥6 months 39% 49% 44% Duration of response (median) 8.3m 4.4m 5.6m Time to response (median) 1.4m 1.4m 1.4m ORR: AT/ATC (n=22/6; 21/9) 32%/33% 24%/33% 28%/33% ORR: TNBC (n=8/10) 25% 50% 39% ORR: visceral disease (n=25/33) 32% 27% 29% ORR: liver metastases (n=19/22) 37% 14% 24% mPFS (n=70) 3.3m 5.3m 4.6m * 4 pts (q14d) w/o on-study scans: excluded from the evaluable population.