tbuckley/cabot-search huggingface dataset:
Presurgical sunitinib in patients with newly diagnosed metastatic renal cell carcinoma (mRCC): Interim toxicity and feasibility analysis.
Authors: E. Jonasch, C. G. Wood, L. C. Pagliaro, P. G. Corn, A. Aparicio, V. D. Marcott, S. F. Matin, N. M. Tannir
Journal: Journal of Clinical Oncology (2010)

e15083 Background: The optimal timing and safety of surgery after targeted therapy is unknown in patients with newly diagnosed mRCC. We report an interim feasibility and safety analysis of a phase II trial in patients with mRCC who undergo nephrectomy during their second cycle of sunitinib. Methods: Patients with biopsy proven clear cell mRCC were treated with one cycle of sunitinib, followed by restaging. Patients underwent nephrectomy between days 14 and 28 of their second cycle, with a 24 hour delay between last dose of sunitinib and surgery. After recovery, patients were restaged and restarted sunitinib a minimum of 14 days postoperatively. A total of 50 patients will be accrued to the trial. The trial estimates that TTP is 8 months, and is evaluated using a continuous monitoring (CM) algorithm. A CM algorithm is also used to evaluate perioperative toxicity, with the assumption that a 12 percent rate of grade 3 perioperative toxicity attributable to sunitinib is considered unacceptable. Results: To date, 28 of 50 patients have been enrolled in an 18 month time period. Of these, 16 have undergone nephrectomy. One of these patients developed a postoperative operative site infection, requiring repeated courses of antibiotics. No other perioperative complications were noted. 9 patients came off study before nephrectomy: two because of drug intolerance, one because of volvulus experienced during cycle 1 of sunitinib requiring surgery, and six because of disease progression after one cycle of therapy. Conclusions: Performing nephrectomy in the context of presurgical sunitinib held 24 hours before surgery is safe and feasible at this interim analysis. Additionally, in a patient group not preselected by prior nephrectomy, a subset demonstrates early progression of disease. These patients can be spared surgery, as their prognosis is poor and are less likely to benefit from nephrectomy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
Vemurafenib treatment in patients with BRAF-mutated melanoma failing MEK inhibition with trametinib.
Authors: Helen Gogas, Dirk Schadendorf, Reinhard Dummer, Claus Garbe, Celeste Lebbe, Paul D. Nathan, James M. G. Larkin, Andrew Mark Haydon, Dimitris Bafaloukos, Caroline Robert
Journal: Journal of Clinical Oncology (2014)

9061 Background: Trametinib was shown to improve progression-free and overall survival in patients with metastatic melanoma with a BRAF V600E or V600K mutation as compared with chemotherapy in the METRIC trial. However, the median duration of response was 5.5 months and median progression-free survival was 4.8 months in the Trametinib group. Vemurafenib and Ipilimumab were still investigational when this trial was initiated but were available in clinical trials for post-protocol treatment. Methods: In this phase III trial 98 patients out of the 322 patients of the intent to treat population who had metastatic melanoma with a V600E or V600K mutation received Vemurafenib (960mg twice daily orally). We present data of patients with complete information on initiation and discontinuation date of Vemurafenib and investigator reported response. Results: With a median follow-up of 18.3 months, the median progression free survival (PFS) was 5.2 months with 95% CI 3.7-5.7 and a range of 0.5-27.5+ months. The 6 months PFS was 40.1%. The median overall survival (OS) was 8.3 months with 95% CI 7.1-10.6 and a range of 0.5-27.5+. The 6 months OS was 68.1%. Nineteen patients achieved a partial response and one a complete response. Conclusions: Treatment with vemurafenib had an impact on progression free survival post trametinib treatment in patients receiving a MEK inhibitor in first or second line setting. Sequencing BRAF inhibitors with MEK inhibitors and combinations are currently under investigation.
Abstract 3904: Left Atrial Appendage Functions in Patients With Hypertrophic Cardiomyopathy and Sinus Rhythm: Transesophageal Echocardiography and Tissue Doppler Study
Authors: Selcen Yakar Tuluce, Meral Kayikcioglu, Kamil Tuluce, Meral Gulsum Yilmaz, Can Hasdemir
Journal: Circulation (2009)

Bacground: Stroke and systemic embolism still remains high in patients(pts) with hypertrophic cardiomyopathy (HCM). Such events are more common in patients with atrial fibrillation (AF). However, i...
Abstract 16405: Long-Term Biological Pacemaker Activity Created by Percutaneous <i>TBX18</i> Gene Transfer
Authors: Yu-Feng Hu, James Dawkins, Hee Cheol Cho, Eduardo Marbán, Eugenio Cingolani
Journal: Circulation (2014)

Background: Minimally-invasive TBX18 gene transfer creates physiologically-relevant biological pacemaker (BioP) activity for at least 2 weeks in pigs with complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically-relevant disease model (Hu et al, Sci Trans Med 2014). It remains unknown how long biological pacemaker activity is maintained after TBX18 gene transfer. Hypothesis: We tested whether TBX18 gene transfer could create sustained BioP activity beyond two weeks. Methods: Adenoviral vectors expressing either TBX18 (n=3) or GFP (n=2) as a control were delivered into the high right ventricular septum via injection catheters (NOGA™ Myostar). Rate and rhythm were followed continuously for one month by implanted telemetry, and backup device utilization was quantified by serial pacemaker interrogations. Physical activity was measured by a built-in accelerometer. Results: BioP activity was evident in TBX18 -transduced animals and persisted at least for 4 weeks. At week 4, maximal heart rate (HR,101±8 vs. 65±3bpm, p&lt;0.05), daytime HR (79±4 vs. 53±1bpm, p&lt;0.05), and electronic pacemaker utilization (82±3 vs. 6±3%, p&lt;0.05) were higher in TBX18 -transduced animals compared to GFP controls. Mean HR was borderline higher in TBX18 -transduced animals compared to GFP controls (HR=70±7 vs. 51±1bpm, p=0.11) as was night-time HR (70±5 vs. 51±0bpm, p=0.07). Mean daily activity tends to be greater in TBX18- transduced group (394±18 vs. 339±12 A.U, p=0.11). There were no significant differences of ventricular arrhythmia incidence between the two groups during 4 week follow-up. Cardiac enzymes, liver function, renal function, and systemic inflammatory markers remained unchanged in both groups during follow-up. Conclusions: TBX18 gene transfer can create stable BioP activity for at least 4 weeks, suggesting a potential long-term BioP effect after adenoviral gene transfer.
A Polylactide Bioresorbable Scaffold Eluting Everolimus for Treatment of Coronary Stenosis
Authors: Patrick W. Serruys, John Ormiston, Robert-Jan van Geuns, Bernard de Bruyne, Dariusz Dudek, Evald Christiansen, Bernard Chevalier, Pieter Smits, Dougal McClean, Jacques Koolen, Stephan Windecker, Robert Whitbourn, Ian Meredith, Luc Wasungu, Divine Ediebah, Susan Veldhof, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2016)
Metachronous second primary cancer after diagnosis of stomach cancer in Daegu Dongsan Medical Center, Korea
Authors: Y. Do, J. Kim, H. Song, Y. Kim, J. Jin, H. Park
Journal: Journal of Clinical Oncology (2008)

15616 Background: The pattern of second primary cancers after treatment for gastric cancer is important for patient's survival. Methods: We analyzed the clinicopathologic data of 5,778 patients with gastric cancer regard to metachronous second primary cancers from October 1996 to November 2007. Results: Of 5,778 patients, 170 metachronous second primary cancer had occurred in 160 patients (2.8%). The median age was 61 years, and the male was 112 (65.9%) and female was 58 (34.1%). The observed/expected rates in male was 1.11 and in female was 1.41 based on Daegu Cancer Resistry. The median time to occurrence of second cancers after diagnosis was 26.8 months (range, 6.2–123.2 months). Most common cancer was colorectal cancer in 36 (21.2%), and lung cancer in 27 (15.9%), hepatoma in 26 (15.3%), ovarian cancer in 15 (8.8%), esophageal cancer in 9 (5.3%), pancreatic cancer in 7 (4.1%), cervical cancer in 6 (3.5%), biliary cancer in 6 (3.5%), thyroid cancer in 5 (2.9%), and non-Hodgkin's lymphoma in 5 (2.9%) in order of frequency. Late second cancers after 5 years was 35 (20.6%). and the hepatoma, lung cancer, and rectal cancer were frequently detected. After 10 years, 2 patients of hepatoma and lung cancer were detected. Conclusions: The present study suggests that the follow up of stomach cancer over 10 years is needed in order to enable the early diagnosis of second primary cancers. No significant financial relationships to disclose.
Polymorphism of collagen I gene and glutation-S-transferases T1 and M1 in chronic obstructive pulmonary disease associated with cardiovascular disease
Authors: Tatyana Tilik, Vera Nevzorova, Svetlana Vakhrusheva, Evgeny Gilifanov, Marina Issaeva, Elena Openchuk, Olga Atamas
Journal: European Respiratory Journal (2011)

The aim of the research was to establish association between presence of mutant genotype COL1A1 (locus G1546T), null-genotypes of glutation-S-transferases (GSTs) GSTM1 and GSTT1 and stage of chronic obstructive pulmonary disease (COPD). The group of patients with COPD (II and III stage of COPD, n=30) associated with I-II functional groups of stable stenocardia (I and II subgroup, n=30) was examined.

In the research of gene COL1A polymorphism pathological allele T was found in 15% of healthy persons. Genotype GT was revealed at 1/3 of control group while pathological homozygous genotype TT in the same group hadn't been registered. In both groups frequency of genotype GT was higher than in the control group (χ 2 =6.5, ρ =0.01). Genotype TT was found in II group only (χ 2 =12, ρ =0.01). The OR of severe COPD in the presence of pathological allele T COL1A1 was authentically higher in II group, than in I (OR=1.74, OR=1.65, accordingly; p <0.05). Patients with pathological genotype of COL1A1 had been screened for the presence of combined null-genotype of GSTs. The homozygous deletion of both genes was found at four patients (all patients from II group). Respectively these patients had pathological genotype GT of COL1A1 demonstrated by functional inadequacy of collagen 1A1. Presence of combined null-genotype GSTM1 and GSTT1 at these patients, in turn, can lead to the total absence of enzymes GSTs, contributing accumulation of toxic intermediate metabolites of xenobiotics in the cell without their further neutralization and development of oxidative stress and destruction of connective tissue.
Abstract 11205: Weight Gain in Infancy is a Key Determinant of Obesity, Blood Pressure and Arterial Thickening in Later Childhood
Authors: Michael R Skilton, Guy B Marks, Julian G Ayer, Frances L Garden, Sarah P Garnett, Jason A Harmer, Stephen R Leeder, Brett G Toelle, Karen Webb, Louise A Baur, David S Celermajer
Journal: Circulation (2012)

Introduction:  Obesity and vascular risk factors in mid and late childhood are significant predictors of adult risk of cardiovascular events. The determinants of early postnatal weight gain, from 0-18 months, and the relationship of early weight gain to atherogenic risk factors in later childhood, are not well characterized.   Hypothesis:  We assessed the hypothesis that early weight gain is an important predictor of overweight/obesity, higher blood pressure, systemic inflammation and arterial wall thickening, in later childhood.   Methods:  We analyzed data from 395 non-diabetic children recruited antenatally, with complete data for early weight gain and arterial wall thickness at age 8-years. To account for differences in weight gain due to height, we adjusted early weight gain for height gain over the same period.   Results:  Independent predictors of early weight gain included male gender (0.378 kg [SE 0.104],  P  P =0.007), birth length (0.158 kg [SE 0.024] per cm,  P  P  P  P =0.007) and greater carotid intima-media thickness (figure). The association with carotid intima-media thickness was independent of childhood BMI (0.010 mm [SE 0.004] per kg,  P =0.02).   Conclusion:  Early weight gain between 0-18 months is a significant predictor of later childhood overweight and obesity, excess central adiposity, and greater arterial wall thickness.
EORTC 18961: Post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results
Authors: A. M. Eggermont, S. Suciu, W. Ruka, J. Marsden, A. Testori, P. Corrie, S. Aamdal, P. A. Ascierto, P. Patel, A. Spatz
Journal: Journal of Clinical Oncology (2008)

9004 Background: EORTC 18961 assessed in the largest adjuvant phase III trial to date in stage II melanoma the efficacy and toxicity of Ganglioside GM2-KLH21 Vaccination (VAC) Treatment vs Observation (OBS). Methods: Patients (Pts) were observed or received vaccine sc once weekly week 1–4, every 3 months from week 12 for first 2 years and every 6 months during third year (total of 14 vaccinations). Stratification factors for randomization were: Breslow thickness, ulceration, being staged yes vs no by Sentinel Node (SNLD) or Elective Lymph Node Dissection (ELND), sex and institution. Relapse-free survival (RFS) was the primary endpoint; Distant metastasis-free survival (DMFS) and overall survival (OS) were the prespecified secondary endpoints. Intent-to-treat analysis was performed. Results: Between March 2002 and Dec. 2005, 1,314 pts entered the trial. Patient demographics showed perfect balance for prognostic factors. The 2nd interim analysis was performed when 267 RFS events were reported, i.e. 67% of the total number required at final analysis. Median follow-up was 1.8 years. Similar treatment differences were obtained in lympnhnode-staged (N=644) or non-staged (N=670) patients. Grade 3 - toxicities occurred in < 2%.(VAC) and in < 1% (OBS). Grade 2 - toxicities comprised fatigue (15% vs 3%), fever (9% vs 1%), nausea (3% vs 1%). Local grade 3 - toxicity occurred in 4 % (VAC). The EORTC IDMC reviewed both safety and efficacy data. For the primary endpoint, RFS, the criteria for stopping for futility were met. For DMFS and OS, the results pointed in the direction of a detrimental effect of the vaccine. The IDMC recommended trial 18961 to be stopped and vaccinations to be halted in pts still receiving VAC. Pts should continue to be followed for the trial's endpoints. Conclusions: Adjuvant GM2-KLH21 vaccination is ineffective and could even be detrimental in stage II melanoma patients. RFS DMFS OS Obs. GM2-KLH21 Obs. GM2-KLH21 Obs. GM2-KLH21 Nb. Events 132 135 65 86 35 56 2-yr % (SE%) 77.8% (1.9%) 75.1% (2.0%) 88.5 (1.6%) 82.4 (1.9%) 92.4 (1.4%) 89.2 (1.7%) HR (CI)(1) 1.02 (0.77-1.36)* 1.33 (0.77-2.28)** 1.57 (0.68-3.64)*** p- value(1) 0.85 0.08 0.03 HR (CI)(2) 1.00 (0.75-1.34)* 1.32 (0.76- 2.30)** 1.66 (0.66-3.99)*** p-value(2) 0.99 0.10 0.02 HR = Hazard Ratio; * 98% CI, ** 99.9% CI, *** 99.99% CI. (1) Cox model, unadjusted for stratification factors; (2) Cox model, stratified for stratification factors No significant financial relationships to disclose.
Clinical significance of brain metastases occurrence in HER2 overexpressing metastatic breast cancer patients treated with trastuzumab
Authors: V. Mari, E. Chamorey, A. Italiano, F. Van Den Bos, R. Ferri-Dessens, J. Ferrero, R. Largillier, F. Ettore, A. Courdi, P. Paquis, M. Frenay
Journal: Journal of Clinical Oncology (2006)

10593 Background: Recent data report that HER2 overexpressing metastatic breast cancer patients (HER+ MBC pts) treated with trastuzumab (T) have a high rate of Brain metastasis (BM). This study aimed to evaluate the prognostic significance of BM occurrence and the related clinical outcome in a specific patient population. Methods: All the HER+MBC patients treated with trastuzumab (with or without chemotherapy) between 09/1999 and 12/2004 were included in this study. Results: A total of forty three patients were enrolled into the study cohort. The median follow-up was 48 months (range, 11–166). Fifteen patients (35%) developped BM. The median interval from the the first MBC event to BM was 18 months (range, 1–65). In multivariate analysis; younger age was the only factor associated with BM occurrence (46 versus 57 years; p = 0.01). Patients with BM tend to have a longer median duration of response to T than patients without BM (16 months versus 13 months; p = 0.1). At the time of BM appearance, 6 of the 15 patients (40%) were still responding or had achieved extracranial stable disease while receiving trastuzumab. Twelve out of 15 (80%) pts received a whole-brain radiation therapy, and 8 pts continued to receive trastuzumab until extracranial disease progression. The median overall survival for patients diagnosed with BM was 10 months (range, 2–42). At three-year, there was no significant difference in overall survival rates between the two groups. The 3-YS was 63.5% and 66.7% for pts with or without BM, respectively; (p = 0.7). Conclusions: The BM occurrence in HER2+ MBC pts treated with Trastuzumab is not linked to tumour resistance, but likely related to the T inability to cross the blood-brain barrier. There is no impaired survival for these pts treated with effective and appropriate therapy. [Table: see text]
Central Nervous System Stromal Cells Control Local CD8 + T Cell Responses during Virus-Induced Neuroinflammation
Authors: Jovana Cupovic, Lucas Onder, Cristina Gil-Cruz, Elke Weiler, Sonja Caviezel-Firner, Christian Perez-Shibayama, Thomas Rülicke, Ingo Bechmann, Burkhard Ludewig
Journal: Immunity (2016)
Association of serum 25-hydroxy vitamin D and body mass index in cancer
Authors: D. Gupta, K. Trukova, P. G. Vashi, A. Adams, G. M. Lambert, C. A. Lammersfeld
Journal: Journal of Clinical Oncology (2009)

6625 Background: The association between vitamin D and obesity remains unsettled with studies reporting conflicting findings on the relationship between the two. This association assumes even greater importance in cancer because of the alleged role of vitamin D in cancer risk and survival. Currently, the dietary recommendations for Vitamin D do not take into account a person's body mass index (BMI). We investigated the relationship between serum 25-hydroxy-vitamin D [25(OH)D] and BMI in a large sample of cancer patients. Methods: A consecutive case series of 740 cancer patients seen at Cancer Treatment Centers of America from Jan 08 to June 08. Serum 25(OH)D was measured at presentation to the hospital. The cohort was divided in 4 BMI groups (&lt;18.5, 18.5–24.9, 25–29.9, and &gt;30.0 kg/m 2 ). Correlation between 25(OH)D and BMI was evaluated using Spearman correlation coefficient. Mean 25(OH)D was compared across the 4 BMI groups using ANOVA. Linear regression was used to quantify the relationship between BMI and 25(OH)D. Results: Of 740 patients, 303 were males and 437 females. The mean age at presentation was 55.7 years (SD = 10.2). The mean BMI was 27.9 kg/m 2 (SD = 6.7). Most common cancers were lung (134, 18.1%), breast (131, 17.7%), colorectal (97, 13.1%), pancreas (86, 11.6%), prostate (45, 6.1%) and ovarian (39, 5.3%). The mean serum 25(OH)D was 21.9 ng/ml (SD = 13.5). Analysis revealed that as BMI groups increased from normal to overweight or obese classifications, there was a significant decrease in 25(OH)D (Table). The Spearman correlation between 25(OH)D and BMI was -0.20 (p = 0.001). Every 1 kg/m 2 increase in BMI was significantly associated with a 0.43 ng/ml decline in serum 25(OH)D (p = 0.001). Conclusions: We found that obese cancer patients (BMI &gt;=30 kg/m 2 ) had significantly lower levels of serum 25(OH)D as compared to nonobese patients (BMI &lt;30 kg/m 2 ). BMI should be taken into account when assessing a patient's vitamin D status and more aggressive vitamin D supplementation should be considered in obese cancer patients. [Table: see text] No significant financial relationships to disclose.
Abstract 871: The association between periodontal disease and pancreatic cancer
Authors: Jeffrey S. Chang, Chia-Rung Tsai, Yan-Shen Shan, Li-Tzong Chen
Journal: Cancer Research (2015)

Abstract Background: Despite years of research, the causes of pancreatic cancer have remained largely unknown. Periodontal disease (PD) is an emerging risk factor for various systemic diseases, including cancer. The current study investigated the association between PD (periodontitis, gingivitis, and others) and development of pancreatic cancer. Methods: Using data from the National Health Insurance Research Database of Taiwan, 139,805 subjects with PD and 75,085 subjects without PD were identified. The association between PD and pancreatic cancer was assessed using Cox proportional hazards regression model. Results: Having PD was associated with a higher pancreatic cancer risk (hazard ratio (HR) = 1.55, 95% confidence interval (CI): 1.02-2.33). The higher pancreatic cancer risk associated with PD was observed among those aged 65 years or older (HR = 2.17, 95% CI: 1.03-4.57) and but not among those aged younger than 65 years (HR = 0.83, 95% CI: 0.52-1.34). Further analysis showed that PD remained an independent risk factor for pancreatic cancer after adjusting for diabetes, hyperlipidemia, allergies, viral hepatitis, peptic ulcer, pancreatitis, COPD (as a proxy for cigarette smoking) and alcoholic-related conditions (as a proxy for alcohol drinking). Conclusions: Our analysis showed a significantly positive association between PD and pancreatic cancer risk. Further investigation is needed to explain the underlying biological mechanisms for the positive association between PD and pancreatic cancer. Citation Format: Jeffrey S. Chang, Chia-Rung Tsai, Yan-Shen Shan, Li-Tzong Chen. The association between periodontal disease and pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 871. doi:10.1158/1538-7445.AM2015-871
Interstitial lung abnormalities are linked to increased risk of death
Authors: Jacqui Wise
Journal: BMJ (2016)

Interstitial lung abnormalities—which are often undiagnosed and asymptomatic—are associated with a greater risk of all cause mortality, US research published in JAMA has shown.1

Interstitial lung abnormalities are defined as specific patterns of increased lung density seen on computed tomography (CT) chest scans in patients with no prior history of lung disease.

Ivan Rosas, of Brigham and Women’s Hospital in Boston, Massachusetts and colleagues examined whether interstitial lung abnormalities were associated with increased mortality in four separate research cohorts. These lung abnormalities were present in 7% of the 2633 participants in the Framingham …
Vitamin D3 and Lenalidomide Synergize To Induce Apoptosis In Mantle Cell Lymphoma Via Demethylation Of BIK
Authors: Carole Brosseau, Christelle Dousset, Cyrille Touzeau, Sophie Maiga, Philippe Moreau, Martine Amiot, Steven Le Gouill, Catherine Pellat-Deceunynck
Journal: Blood (2013)
Adipose Tissue Insulin Resistance is Associated with Macrophage Activation in Non-Diabetic Patients with Non-Alcoholic Fatty Liver Disease
Authors: C. Rosso, K. Kazankov, M. Gaggini, C. Saponaro, M. Marietti, H.J. Møller, G.P. Caviglia, E. Buzzigoli, M.L. Abate, A. Smedile, G.M. Saracco, H. Vilstrup, J. George, A. Gastaldelli, H. Grønbæk, E. Bugianesi
Journal: Journal of Hepatology (2016)
Could drugs inhibiting the mevalonate pathway also target cancer stem cells?
Authors: Wirginia Likus, Krzysztof Siemianowicz, Konrad Bieńk, Małgorzata Pakuła, Himani Pathak, Chhanda Dutta, Qiong Wang, Shahla Shojaei, Yehuda G. Assaraf, Saeid Ghavami, Artur Cieślar-Pobuda, Marek J. Łos
Journal: Drug Resistance Updates (2016)