tbuckley/cabot-search huggingface dataset:
Cure fractions (CF) modeled from event-free survival and complete response duration plots in total therapy (TT) trials for newly diagnosed multiple myeloma (MM).
Authors: J. Crowley, J. D. Shaughnessy, V. Bolejack, E. J. Anaissie, F. Van Rhee, B. Barlogie
Journal: Journal of Clinical Oncology (2010)

8119 Background: We recently reported that survival outcomes in TT protocols were compatible with progressively increasing CF with the transition from TT1 initiated in 1989 to TT2 started in 1996 and TT3 begun in 2003 (Barlogie et al, ASH 2009). Methods: Mathematical models were applied to fit event-free survival (EFS) and CR duration (CRD) plots with a cure plateau and exponentially declining survival. Cox regression analysis was applied to determine odds ratio (OR) values of CF. Results: In TT1,CF- EFS was 9.4% (p<0.0001) and CF-CRD 14.6% among the 94 CR patients (p=0.0003), with higher values in the absence of cytogenetic abnormalities (CA) (CF-EFS: 11.7% v 3.5%; CF-CRD: 17.2% v 9.6%). In TT2, CF-EFS was 16.5% (p=0.0008) and CF-CRD was 27.6% among 351 attaining CR (p=0.001). CA affected CF-CRD (no CA: 27.8%, p=0.06; CA: 15.8%, p=0.06) but not CF-EFS. In the context of GEP, significant CF-EFS (14.3%, p=0.01) and CF-CRD (26.6%, p=0.03) were observed only in the high-risk setting. With regard to thalidomide, CF-EFS was superior when patients were randomized to thalidomide (23.2%, p=0.003 v 9.9%, p=0.121), which also applied to CF-CRD (31.4%, p=0.009 v 22.4%, p=0.07). In TT3, CF-EFS was 52.7% (p<0.0001) and CF-CRD among 188 CR patients 65.5% (p=0.02) which, when examined in context of GEP, only applied to low-risk myeloma (CF-EFS=61.1%, p<0.0001; CF-CRD=87.6%, p=0.0001). Multivariate analysis of protocols and baseline variables identified significant odds ratio (OR) values for cure in case of TT2 plus thalidomide (OR=0.296, p=0.03), TT3 (OR=0.079, p<0.0001), whereas cure-adverse variables were CA (OR=2.411, p=0.03) and albumin <3.5g/dL (OR=3.374, p=0.03). Conclusions: This is the first report on multivariate modeling for CF in MM, revealing major cure contributions from thalidomide in TT2 and added bortezomib in TT3 whereas, among the non-cured patients, CA and low albumin increased the risk of recurrence and death. No significant financial relationships to disclose.
Regulation of the c-jun Gene in p210 BCR-ABL Transformed Cells Corresponds With Activity of JNK, the c-jun N-Terminal Kinase
Authors: Gem S. Burgess, Elizabeth A. Williamson, Larry D. Cripe, Sara Litz-Jackson, Jay A. Bhatt, Kurt Stanley, Mark J. Stewart, Andrew S. Kraft, Harikrishna Nakshatri, H. Scott Boswell
Journal: Blood (1998)
Prognostic values of micrornas in patients with Dukes' B and C colon cancer.
Authors: M. Karaayvaz, T. Pal, B. Song, C. Zhang, P. Geogakopoulos, S. Mehmood, S. Burke, K. Shroyer, J. Ju
Journal: Journal of Clinical Oncology (2010)

3586 Background: Translational control mediated by noncoding microRNAs plays a key role in resistance to anticancer drug treatment. As a result, non-coding microRNAs hold great potential as new prognostic biomarkers. Previous studies from our laboratory have revealed that chemotherapeuric targets thymidylate synthase (TS) and dihydrofolate reductase (DHFR) were suppressed by miR-192 and miR-215 in colorectal cancer. miR-192 and miR-215 are candidate tumor suppressors due to the up-regulation of p53 and p21. The goal of this study is to find miRNAs as potential prognostic biomarkers in archival FFPE clinical samples of patients with stage II and III colon cancer. In this study, the expression of candidate miRNAs (let-7g, miR-21, miR-192, miR-215) was quantified from 15 stage II and 19 stage III colon specimens with up to 10 years clinical follow up information. Methods: Total RNAs were extracted from 34 paired normal and colon tumor specimens (stage II and III) using Trizol based approach. The levels of miRNAs were quantified using real time qRT-PCR expression analysis. Results: The expression of miR-192 (p = 0.0028) and miR-215 (p = 0.0001) was significantly decreased in colon tumors compared to normal adjacent mucosa. The expression of miR-21 was significantly elevated in colon tumor specimens (p = 0.0001). Kaplan-Meier survival analysis revealed that high levels of miR-215 expression (hazard ratio, 0.36; log rank test, p = 0.04) are closely associated with better patient's overall survival. Conclusions: miR-215 holds a great potential as prognostic biomarker in stage II and III colon cancer. No significant financial relationships to disclose.
Immunologic Effects of BCG in Patients With Malignant Melanoma: Specific Evidence for Stimulation of the “Secondary” Immune Response
Authors: Leonard Chess, Gerald N. Bock, Peter C. Ungaro, Donald H. Buchholz, Michael R. Mardiney
Journal: JNCI Journal of the National Cancer Institute (1973)

The effects of BCG vaccine on immunologic function were assessed in 4 patients with malignant melanoma. Cell-associated immune function was quantitatively measured in vitro by the incorporation of 3H-thymidine into frozen-stored lymphocytes in response to specific antigens (both related and unrelated to BCG), allogeneic lymphocytes, and phytohemagglutinin (PHA). In vivo, cell-mediated immunity was determined by delayed hypersensitivity skin reactions to various antigens. Serum IgG, IgM, IgA, and C'3 (complement) levels were quantitated. BCG administration significantly augmented antigen-induced incorporation of 3H-thymidine in 3 patients, with little or no effect on responses to allogeneic lymphocytes or PHA. BCG selectively increased serum IgG levels in the same 3 patients. IgA, IgM, or complement levels were not enhanced. All patients converted their purified protein derivative (PPD) skin-test reactivity from negative to positive during therapy, and in 2 patients candida skin reactivity appeared. These effects on cell-associated immune functions, immunoglobulin, complement levels, and in vivo-delayed hypersensitivity were consistent with the hypothesis that BCG primarily augments host responsiveness to antigens to which the host has previously been exposed. No effect on the primary immune response was detected. The 1 patient who did not respond to BCG by either cell-associated humoral immunologic enhancement had metastatic disease before initiation of study, which then rapidly progressed. Clinically, 2 of the 3 patients reacting immunologically, in addition to the 1 patient who failed to respond, developed progressive metastatic disease during therapy. One patient continues to respond immunologically and remains Free of progressive disease.
Diet rich in carotenoids is linked to reduced risk of advanced age related macular degeneration
Authors: Jacqui Wise
Journal: BMJ (2015)

A higher intake of carotenoids, particularly lutein and zeaxanthin, is associated with a long term reduced risk of developing advanced age related macular degeneration (AMD), two large prospective cohort studies published in JAMA Ophthalmology have shown.1

Carotenoids are fat soluble plant pigments found in red, yellow, orange, and dark green fruits and vegetables. The best sources of lutein and zeaxanthin are green leafy vegetables such as kale, …
Social support and subsequent mortality among patients with end-stage renal disease.
Authors: W M McClellan, D J Stanwyck, C A Anson
Journal: Journal of the American Society of Nephrology (1993)

The association between social support in newly entered dialysis patients and their subsequent risk of mortality was investigated. Two hundred forty-nine dialysis patients were enrolled from dialysis facilities in two southeastern states. A score was calculated for the amount of social support a patient reported giving and receiving from spouse, family, friends, nurses, physicians, staff, and fellow patients. Patients were monitored for 12 months after enrollment into the cohort: 43 (17.6%) died. Mean (SD) scores for giving support to the family were higher among survivors, 3.59 (0.92), than among those who died, 3.17 (1.32) (P = 0.022). Mean scores for giving support to friends were also higher among survivors, 3.38 (1.13), than among nonsurvivors, 2.94 (1.33) (P = 0.044). After other factors associated with increased risk of dying, including age, sex, race, diabetic renal disease, angina pectoris, and functional status, were controlled for, individuals in the lowest quartile of giving social support to friends continued to have a greater risk of dying, with adjusted relative risk (95% confidence interval) = 2.02 (1.01, 4.07). In contrast, there were no differences in risk of death found for differing levels of receiving social support. It was concluded that social support is an independent risk factor for mortality among new dialysis patients.
Role of Hormones in the Etiology of Breast Cancer<xref ref-type="fn" rid="FN1">1</xref>
Authors: O. Mühlbock
Journal: JNCI Journal of the National Cancer Institute (1972)

Experimental investigations have indicated that hormones may be carcinogenic. Generally speaking, only hormones stimulating growth are carcinogenic. This carcinogenic effect can be expected mainly in the target organ of the particular hormone. Hormones with carcinogenic potentiality are the trophic hormones of the hypophysis and the steroid hormones, especially the estrogenic hormones. Of great importance in the genesis of mammary tumors is the cooperative effect of estrogenic hormones, progesterone, and prolactin. The significance of the hormonal factors in the genesis of human breast cancer and the methods for the determination of these factors are discussed.
Exon-specific gene correction (conversion) during short evolutionary periods: homogenization in a two-gene family encoding the beta-chain constant region of the T-lymphocyte antigen receptor.
Authors: S Rudikoff, W M Fitch, M Heller
Journal: Molecular Biology and Evolution (1992)

The two genes encoding the beta-chain constant region of the T-lymphocyte antigen receptor appear to have undergone gene conversion in a number of species, including wild and laboratory mice. To examine the frequency of such events during short evolutionary periods, we have characterized the corresponding genes from an African pygmy mouse, Mus minutoides. Sequence analysis indicates that exon 1 regions from these genes have undergone conversion events independent of those observed in other mouse species. Furthermore, the conversion events in all murine species are limited to exon 1 sequences. One such event involves the insertion and subsequent transfer of an entire codon between the two genes. Comparisons with other murine C beta sequences suggest that gene conversion has occurred on the order of every 0.3 Myr during the evolution of a family consisting of only two genes.
Radiation therapy is better than chemotherapy in early-stage Hodgkin's disease? Not so fast.
Authors: D L Longo, P L Duffey, S M Hubbard, R C Young, V T DeVita
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.8.1367 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1634930 Radiation therapy is better than chemotherapy in early-stage Hodgkin's disease? Not so fast. D L LongoxD L LongoSearch for articles by this author , P L DuffeyxP L DuffeySearch for articles by this author , S M HubbardxS M HubbardSearch for articles by this author , R C YoungxR C YoungSearch for articles by this author , V T DeVita JrxV T DeVita JrSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.8.1367 First Page PDF © 1992 by American Society of Clinical Oncology
Comparison of progression-free survival (PFS) with best or confirmed response (BR, CR) as an endpoint for overall survival (OS) in advanced non small cell lung cancer (A-NSCLC): A North Central Cancer Treatment Group (NCCTG) investigation
Authors: S. J. Mandrekar, S. L. Hillman, K. L. Allen Ziegler, N. F. Reuter, K. M. Rowland, R. S. Marks, S. E. Schild, A. A. Adjei
Journal: Journal of Clinical Oncology (2008)

8021 Background: Historically, tumor response has been the primary endpoint in Phase II (P2) trials in A-NSCLC. With targeted therapies that prolong disease stabilization, PFS rate has become an accepted alternate endpoint. We investigated the relationship between PFS, BR, and CR with OS to assess their suitability as endpoints in P2 trials. Methods: Individual patient (pt) data from 343 pts from 4 first line A-NSCLC P2 NCCTG treatment trials were pooled. The trial regimens included Docetaxel, Gemcitabine, Pemetrexed, Temsorilimus and Sorafenib. Any pt who progressed prior to 6 months (m) but lived beyond 12 m or progressed after 6 m but died before 12 m was considered discordant (D). Percent agreement (PA) between PFS rate, BR, and CR with OS at 12 m was calculated on a per-pt basis, and the predictive utility assessed using the area under the receiver-operating characteristic curve (A-ROC) in logistic models. Patterns in baseline pt and tumor characteristics and subsequent therapy (ST) between the concordant (C) and D subgroups were evaluated. Results: The 12 m OS and the 6 m PFS rates were 40% and 33%. The median time from progression to death was 5.4 m. The PA (A-ROC) for PFS at 6 m, BR and CR was 78% (0.76), 63% (0.58) and 65% (0.59) respectively. 72% of pts in the D group versus only 61% in the C group had ST (p=0.09). Pts with discordant outcomes had a lesser median tumor burden at baseline (6.0 vs. 6.6, p=0.2) and longer median time to progression (TTP) (136 vs. 116 days; log rank p=0.03). No differences by age, gender, ECOG performance status or tumor stage were found. Conclusions: PFS is more predictive of OS than BR or CR for P2 trials in A-NSCLC. Discordant pts had lesser tumor burden, longer TTP on first line treatment and more ST. Such heterogeneity in pt population makes randomized P2 trials more suitable in A-NSCLC. No significant financial relationships to disclose.
The impact of pre-radiotherapy surgical intervention on radiation-induced lung injury
Authors: L. B. Marks, Z. Kocak, X. Yu, S. Zhou, D. Hollis, R. J. Folz, K. Light, D. Kahn, A. Tisch, T. Shafman
Journal: Journal of Clinical Oncology (2004)

7274 Background: To assess the impact of thoracic surgical intervention prior to RT on the later development of symptomatic RT-associated lung injury. Methods: From 1991–2003, 251 patients with lung cancer were enrolled on a prospective study to assess RT-induced lung injury. All patients received 3D-planned external beam RT at Duke. 184 patients with >6 month follow-up were eligible for this analysis. 58 patients (32%) had surgical intervention (thoracotomy without resection, wedge resection, lobectomy, and pneumonectomy) prior to RT. The rates of grade ≥2 symptomatic pneumonitis in patient subgroups, based on the type of pre-RT surgery, were computed and compared via Fishers Exact Test. To consider the confounding factor of irradiated lung volume, patient subgroups were further defined based on the mean lung dose. Thus, within a defined range of mean lung doses, the rates of pneumonitis in the different surgical groups were compared. Results: See Table. In the lobectomy group, the pneumonitis rates in patients with right and left sided tumors were 1/9 and 6/14, respectively (p= 0.18).Conclusions: For patients undergoing surgical intervention, the incidence of pneumonitis appears highest in the lobectomy group; especially for left-sided lesions. The rate of pneumonitis appears lowest in patients with a prior pnemonectomy, likely due to their lower mean lung doses. Additional work is needed to better understand the impact of pre-RT surgery on the later development of symptomatic radiation pneumonitis. Supported by NIH R01 Grant CA69579. Thanks to UNC for PLUNC software. No significant financial relationships to disclose.
Abstract P203: Association of Sleep Characteristics with Heart Rate Variability: Chicago Area Sleep Study
Authors: Mercedes Carnethon, Kristen L Knutson, Jason Ng, Peter J de Chavez, Kwang-Youn Kim, Kiang Liu, Phyllis Zee, Jeffrey J Goldberger
Journal: Circulation (2012)

Introduction: Autonomic nervous system (ANS) dysfunction may contribute to the elevated incidence of hypertension, diabetes and coronary heart disease (CHD) among persons with shortened sleep duration. However, prior studies were conducted in adults who had obstructive sleep apnea (OSA), a correlate of short sleep, or using experimental designs that restricted sleep. To explore whether sleep duration is associated with ANS function in adults free from OSA, we tested whether sleep duration was associated with heart rate variability (HRV) indices that represent autonomic modulation of heart rate. Methods: The Chicago Area Sleep Study (CASS) identified men and women ages 35-64 via commercially available telephone listings. Data from 406 participants who had an apnea/hypopnea index&lt;15 based on 1 night of in-home apnea detection (ApneaLink TM ) were studied. Participants wore wrist actigraphs for 7 days (Actiwatch TM ) to determine average sleep duration, sleep percentage (% of time during overnight sleep interval spent sleeping) and minutes of wake after sleep onset (WASO). A validated questionnaire, the Epworth Sleepiness Scale (ESS), was used to determine daytime sleepiness. Electrocardiograms were continuously recorded from participants for 10 minutes s from supine participants; time and frequency domain HRV indices were calculated from the RR interval to estimate overall autonomic modulation of heart rate (standard deviation of normal RR intervals [SDNN]) and parasympathetic modulation heart rate (high frequency power [HF], square root of the mean squared difference of successive R-R intervals [rMSSD]). Height and weight were measured and hypertension and diabetes were determined according to JNC-VII and American Diabetes Association 2010 criteria, respectively. Results: Participants’ mean age was 47.5 years, and 56% were female. Average sleep duration was 7.03 hours (SD=1.15), sleep percentage was 83% (SD=20.1), WASO was 41.4 min (SD=21) and the ESS score was 6.75 (SD=4.1). Following adjustment for age, race, sex, BMI, hypertension, diabetes, physical activity and smoking, sleep duration (per 1 hr) was significantly (p&lt;0.01) inversely associated with SDNN (β=−2.5, SE=1.12), rMSSD (β=−2.6, SE=1.1) and log-transformed HF (β=−0.11, SE=0.05). Findings were similar in the subset of 285 participants with AHI&lt;5. Conclusions: In contrast to prior studies, shorter sleep duration was associated with more favorable parasympathetic modulation of HR. These unexpected findings may suggest that ANS dysfunction associated with OSA may be attributed to hypoxemia rather than the direct effects of shortened sleep duration.
Use of AGS-16M8F as a novel antibody drug conjugate (ADC) for treating renal cancers.
Authors: J. M. Gudas, M. Torgov, Z. An, X. C. Jia, K. J. Morrison, R. K. Morrison, M. Vincent, P. Yang, S. B. Kanner, A. Jakobovits
Journal: Journal of Clinical Oncology (2010)

e15014 Background: AGS-16 is a novel transmembrane antigen discovered by Agensys using transcription profiling that is expressed in kidney and other cancers. A fully human IgG2k monoclonal antibody that binds to AGS-16 with high affinity was conjugated to the anti-microtubulin drug monomethyl auristatin F (MMAF) via a noncleavable maleimidocaproyl (mc) linker to yield the antibody drug conjugate, AGS-16M8F. Methods: In vitro studies were performed to evaluate the binding affinity, species cross reactivity and cell cytotoxicity of AGS-16M8F. The pharmacokinetics (PK) and anti-tumor activity of AGS-16M8F was evaluated using multiple well-established patient-derived and cell line models of renal clear cell carcinomas. In addition, the expression of AGS-16 protein in patient kidney cancer specimens was confirmed using IHC analysis of individual specimens and tissue microarrays. Results: AGS-16M8F bound with high affinity (Kd = 0.3 nM) to both human and cynomolgus monkey AGS-16. Following cell surface binding, AGS-16M8F was internalized and trafficked to lysosomes where catabolism resulted in the release of active drug metabolite. AGS-16M8F mediated potent cell cytotoxicity in vitro and led to significant and prolonged growth inhibition or complete eradication of multiple, large established renal cancer xenograft models, including those grown orthotopically. Results from pharmacokinetic analyses demonstrated that AGS-16M8F was stable in vivo. Finally, IHC analysis confirmed that AGS-16 was highly expressed in more than 80% of renal cancers including both clear cell and papillary carcinomas. Conclusions: When considered together these data indicate that AGS-16M8F is a promising therapeutic ADC for the treatment of renal and other AGS-16 expressing cancers. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agensys Inc.
Abstract P120: Omega-3 Fatty Acid Supplementation in Middle-Aged Adults Reduces Cardiometabolic Risk in Men but not Women
Authors: Claire Newlon, Matthew Muldoon, Susan Sereika, Dora Kuan
Journal: Circulation (2014)

Background: Greater consumption of omega-3 fatty acids has been associated with lower cardiovascular disease risk. Randomized controlled trials indicate direct, albeit small, beneficial effects of omega-3 fatty acids on plasma triglycerides and blood pressure, yet few studies have tested their impact on insulin resistance and the clustered risk factors comprising the metabolic syndrome. Hypothesis: Short-term supplementation with marine omega-3 polyunsaturated fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) will improve aggregated cardiometabolic risk (CMR) in healthy middle-aged adults Methods: We conducted a double-blind, placebo-controlled, parallel group clinical trial. Subjects were 30-54 year-old adults free of atherosclerotic disease and diabetes whose intake of EPA and DHA totaled &lt;300 mg/day. Each was randomly assigned to daily fish oil supplements (2g/day containing 1000 mg EPA and 400mg DHA) or matching soybean oil placebo for 18 weeks. Aggregate CMR at baseline and post-intervention was calculated as the standardized sum of standardized distributions of blood pressure, BMI, and fasting serum triglycerides, glucose, and HDL (reverse scored). Missing data due to dropouts (n=17) and outliers (1-6 per variable) were replaced by multivariate imputation. Outcome analyses were conducted with linear regressions of all randomized subjects based on intention-to-treat. Results: Participants were 272 healthy adult (57% (154 out of 272) women; 17% (47 out of 272) minority; mean age 42) Pittsburgh-area residents. At baseline, demographics, health parameters, physical activity and EPA and DHA consumption did not differ significantly between treatment groups. No overall treatment effect was found, whereas gender moderated the effects of treatment on CMR risk (gender, p=.001 and gender*treatment interaction term p=.011). In gender-specific analyses, supplementation lowered CMR risk relative to placebo in men(p=.036, effect size=.629, standard error (SE) =.282) but not women (p=.168, effect size .261, SE=.222). Of the individual CMR variables, only HDL-cholesterol in men revealed a significant improvement (p=.012). In men receiving placebo, HDL-cholesterol fell by 1.1 mg/dl, whereas in those receiving fish oil, HDL rose by 1.7 mg/dl. As has been noted in other samples, compared to women men had greater CMR and lower HDL-cholesterol. Conclusions: Increased intake of n-3 fatty acids over 4 months reduced CMR in healthy, mid-life men but not women. This finding may be due to poorer baseline CMR and HDL characteristic of men, or to gender differences in fatty acid metabolism. Further study of gender differences in cardiometabolic risk and fatty acid metabolism may lead to gender-tailored preventive interventions.