tbuckley/cabot-search huggingface dataset:
Evolution of management of testicular seminoma: Population-based outcomes with decreased utilization of active therapies.
Authors: C. R. Nichols, S. Tyldesley, C. J. Moore, K. N. Chi, N. Murray, S. Daneshmand, P. C. Black, B. M. Hayes-Lattin, C. K. Kollmannsberger
Journal: Journal of Clinical Oncology (2010)

4536 Background: The British Columbia Cancer Agency and the Oregon Testicular Cancer Program utilize uniform guideline-driven care for their respective populations of patients (pts) with testicular cancer. We herein report the evolution of treatment and associated outcomes of SEM in a contemporary population-based cohort. Methods: All pts with histologically confirmed pure SEM referred between 1999 and 2008 to either institution were retrospectively reviewed. Both institutions manage approximately 90% of testicular cancers in their respective area. Results: A total of 649 pts were managed from 1999-2008. Clinical stage (CS) distribution: CSI n=545, CSII n=87 and CSIII n= 17. For CSI pts there was a progressive and marked decrease in the utilization of prophylactic radiation (RT), and increased use of active surveillance (SURV). No deaths related to SEM were reported among these 313 pts undergoing SURV with median follow-up of 39 months (Table). 104 pts presented with CSII or CSIII disease and received RT or IGCCCC risk appropriate chemotherapy (ChT). Among this group, 101/104 pts are in long-term remissions with 3 pts dying from treatment complications. For the entire SEM population, < 1% of pts died from their disease or treatment after a median follow-up of 47 months (2-130) (Table). Conclusions: Progressive application of policies of active SURV, and earlier initiation of IGCCC risk adapted CT results in nearly universal control for all pts presenting with SEM while reducing the burden of treatment. Results of SEM treatment 1999-2008 Evolutions of patterns of care 1999-2007 (n=649) Year Outcome of pts treated for SEM from 1999 to 2008 99/00 01/02 03/04 05/06 07/08 Relapse N (%) Second relapseN (%) NED N (%) DOD/treatmentN (%) Death other cause N (%) CS I surv n = 313 46% 41% 52% 71% 75% 47 (15%) 3*(<1%) 311 (99%) 0 2 (1%) CSI I RTn = 159 48% 52% 35% 6% 8% 4 (3%) 0 158 (99%) 0 1 (1%) CS I carboplatinn = 73 6% 7% 13% 23% 17% 1 (1%) 0 73 (100%) 0 0 CS II RTn = 19 44% 34% 36% 14% 0 3 (16%) 0 18 (97%) 0 1 (3%) CS II ChTn = 65 56% 66% 64% 86% 100% 1 (2%) 0 60 (92%) 3 (5%) 2 (3%) CS II other n = 3 100% 0 0 0 0 0 0 3 (100%) 0 0 CS III ChTn = 17 100% 100% 100% 100% 100% 0 0 17 (100%) 0 0 Abbreviations: NED, no evidence of disease; DOD, dead of disease. * After RT for first relapse. No significant financial relationships to disclose.
Abstract 13264: Inhibition of Class I HDACs Suppresses Fibrogenesis by Repressing Tgf-{beta}1-induced Smad Activation in Cardiac Fibroblasts
Authors: Dan L Li, R. H Naseem, Annie Nguyen, Thomas G Gillette, Joseph A Hill
Journal: Circulation (2013)

Introduction: Cardiac fibrosis is a hallmark feature of pathological cardiac remodeling, contributing to contractile dysfunction and arrhythmogenesis. We have shown previously that HDACs (histone d...
Essential Components of Cancer Education
Authors: Danny R. Welch, Toni M. Antalis, Kerry Burnstein, Linda Vona-Davis, Roy A. Jensen, Harikrishna Nakshatri, Anna T. Riegel, Douglas R. Spitz, Dennis K. Watson, George J. Weiner
Journal: Cancer Research (2015)

Modern cancer therapy/care involves the integration of basic, clinical, and population-based research professionals using state-of-the-art science to achieve the best possible patient outcomes. A well-integrated team of basic, clinical, and population science professionals and educators working with a fully engaged group of creative junior investigators and trainees provides a structure to achieve these common goals. To this end, the structure provided by cancer-focused educational programs can create the integrated culture of academic medicine needed to reduce the burden of cancer on society. This summary outlines fundamental principles and potential best practice strategies for the development of integrated educational programs directed at achieving a work force of professionals that broadly appreciate the principals of academic medicine spanning the breadth of knowledge necessary to advance the goal of improving the current practice of cancer care medicine.
Altered etoposide pharmacokinetics and time to engraftment in pediatric patients undergoing autologous bone marrow transplantation.
Authors: J H Rodman, D J Murry, T Madden, V M Santana
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the pharmacokinetics and clinical response of high-dose etoposide in combination with carboplatin for pediatric cancer patients undergoing autologous bone marrow transplant. PATIENTS AND METHODS Pharmacokinetic parameters for etoposide were determined at doses of 960, 1,200, and 1,500 mg/m2 when given with high-dose carboplatin and followed by autologous marrow rescue. Twenty-nine patients (age 1.6 to 23 years) with refractory or relapsed solid tumors were studied. Etoposide was administered in three divided doses as a 6-hour infusion on alternate days with carboplatin. Etoposide concentrations (n = 14) were determined during and following each of three doses. Patient characteristics, drug dose, and pharmacokinetic parameters were examined as predictors of marrow engraftment as reflected by recovery of granulocytes and platelets. RESULTS The median values for clearance (Cl) and terminal half-life (T1/2 beta) of etoposide were 14.3 mL/min/m2 (range, 6.8 to 29.6) and 5.9 hours (range, 3.7 to 39). After adjustment for body size, Cl and volume of distribution did not correlate with any laboratory parameter or patient characteristic. However, seven patients who received concomitant anticonvulsant therapy had significantly higher (P &lt; .01) average etoposide Cl values (23.7 mL/min/m2) than 22 patients who did not receive drugs known to alter hepatic metabolism (13.4 mL/min/m2). The median etoposide Cl value in patients who received concurrent carboplatin but no anticonvulsant agents is substantially lower than values previously reported in either children or adults. Higher etoposide concentrations were significantly associated with longer times to recovery of granulocyte and platelet counts. CONCLUSION Etoposide Cl is significantly higher in patients who receive concomitant anticonvulsant therapy, which is consistent with clinically important hepatic enzyme induction. The lower etoposide Cl associated with high-dose carboplatin suggests that carboplatin may impair etoposide metabolism. Furthermore, high etoposide concentrations appeared to prolong time to recovery of hematopoietic function.
A validated risk model for early neutropenic events in older cancer patients receiving systemic chemotherapy
Authors: M. Shayne, E. Culakova, D. C. Dale, M. S. Poniewierski, D. A. Wolff, J. Crawford, H. Lyman
Journal: Journal of Clinical Oncology (2007)

9036 Background: A prospective, nationwide study was undertaken to develop and validate a risk model for early neutropenic events (NE) in older cancer patients undergoing chemotherapy. Methods: 1,386 patients =65 years of age with lung, breast, colorectal, ovarian cancer or lymphoma were prospectively registered at 117 randomly selected sites. Data on up to 4 cycles were collected upon initiation of chemotherapy. A logistic regression model for cycle 1 NE consisting of febrile neutropenia (FN; fever/infection and absolute neutrophil count nadir &lt;1x10 9 /L) or severe neutropenia (SN; neutrophils &lt;.5x10 9 /L) was derived on 1,378 patients with available data. Validation was performed using a split sample random selection process. Results: No significant differences in distribution of NE or predictive factors were observed between derivation dataset (n=922) and validation dataset (n=464). Major independent baseline clinical risk factors for cycle 1 NE in the derivation model (DM) included: anthracycline based regimens (p&lt;.001), non-chemotherapy immune-modulatory agents (p=.003), elevated bilirubin (p=.016), reduced glomerular filtration rate (p&lt;.001), cancer type (p=.02), planned relative dose intensity =85% (p=.027), and regimens containing cyclophosphamide (p&lt;.001), etoposide (p=.002) or ifosfamide (p=.032). Reduced risk of cycle 1 NE was associated with myeloid growth factor (MGF) prophylaxis (p&lt;.001). DM R 2 was 0.478 and c-statistic 0.88 [95% CI 0.86–0.91; p&lt;.001]. At median predicted risk of cycle 1 NE of 7%, model test performance (MTP) showed: sensitivity 90%; specificity 59%; and predictive value positive and negative of 32% and 97%, respectively. Cycle 1–4 FN risk in the DM was 16.6% and 3.3% among high and low risk patients, respectively. The validation model (VM) R 2 was 0.508 and c-statistic 0.89 [95% CI: 0.86–0.93; p&lt;.001]. MTP in the VM demonstrated: sensitivity 90%; specificity 65%; predictive value positive and negative of 36% and 97%, respectively. Cycle 1–4 FN risk in the VM was 16.8% and 1.6% in high and low risk patients, respectively. Conclusions: This validated risk model demonstrated good discrimination between older cancer patients at decreased risk for NE, and those at increased risk who may benefit from targeted prophylaxis with MGF. No significant financial relationships to disclose.
Long-term sequelae of conservative treatment by surgery, brachytherapy, and chemotherapy for vulval and vaginal rhabdomyosarcoma in children.
Authors: F Flamant, A Gerbaulet, C Nihoul-Fekete, D Valteau-Couanet, D Chassagne, J Lemerle
Journal: Journal of Clinical Oncology (1990)

Between 1970 and 1978, 17 girls with rhabdomyosarcoma (RMS) of the vulva or vagina were treated at the Institut Gustave-Roussy (IGR) by conservative treatment including surgery, brachytherapy, and chemotherapy. Twelve pubescent or postpubescent girls were studied for long-term sequelae. Eleven of 12 patients have had a normal puberty, two have a total of three healthy children, 11 have normal menses, and 10 normal menarche (one after hormonal replacement). Only one patient underwent hysterectomy following low-dose brachytherapy. Five girls have no vaginal complications, and three are sexually active. Three have had minimal vaginal sequelae, which required surgical correction to permit sexual intercourse. Four girls sustained serious sequelae (colorectal, vaginal, urethral, and ureteral stenosis). These sequelae, secondary to irradiation, are potentially avoidable in the future given the current advances in brachytherapy and improvements in dosimetry. This conservative treatment is useful and appropriate for girls with RMS of vulvar or vaginal origin when complete remission cannot be obtained with chemotherapy and partial colpectomy.
Salivary biomarkers for pancreatic cancer detection
Authors: D. T. Wong, L. Zhang, J. Farrell, H. Zhou, D. Elashoff, K. Gao, B. Paster
Journal: Journal of Clinical Oncology (2009)

4630 Pancreatic cancer is the 4th leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. We evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for pancreatic cancer detection. Biomarker discovery strategies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133+2.0 array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P &lt; 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P &lt; 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. More importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P &lt; 0.0001) with 92.9% sensitivity and 85.5% specificity. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer. No significant financial relationships to disclose.
Prediction of response to therapy with clarithromycin/lenalidomide/dexamethasone (BIRD) in multiple myeloma using FDG-PET
Authors: M. Coleman, L. Kostakoglu, S. J. Goldsmith, M. Liu, P. Christos, D. S. Jayabalan, R. Niesvizky
Journal: Journal of Clinical Oncology (2006)

17530 Background: End points based on functional imaging data hold promise to better define and stratify response. As a metabolic imaging modality, FDG-PET can characterize tumor aggressiveness and thus can serve as an early surrogate for therapy response. The combination therapy with BIRD augments tumor mass reduction and improves response in patients with multiple myeloma (MM). The purpose of this study is to determine the value of pre-therapy FDG-PET in predicting therapy response in MM patients undergoing BIRD therapy. Methods: A total of 13 patients with MM (mean age: 60 ± 11) underwent a whole body FDG-PET scan at initial staging prior to BIRD therapy. FDG uptake was qualitatively evaluated in 5 different patterns:minimally diffuse (score 1), focal (score 2), multifocal (score 3), diffuse (score 4) and extramedullary (score 5). Standardized uptake values (SUVmax) were obtained in osseous and extramedullary lesions for quantitative evaluation. Mean SUVmax were also calculated in 14 representative anatomic sites in the axial and appendicular skeleton in 20 age-matched control patients with no osseous malignancy. Ratios of the mean lesion SUVmax to the mean SUVmax in corresponding osseous sections from the control group were calculated. A score was obtained for each patient to reflect disease extent or severity by adding the ratios for each individual lesion. The qualitative and quantitative scores were correlated with the standard response criteria. Results: The results are summarized in the following Table . The pre-therapy qualitative and quantitative scores correlated well with the percent therapy response to BIRD regimen (r = −0.58, p = 0.04 and r = −0.53, p = 0.06, respectively). Conclusions: The pre-therapy FDG-PET scoring system we have developed appears to correlate with the subsequent therapy response to BIRD regimen. Expanded number of patients are warranted to confirm the results of this study. [Table: see text] No significant financial relationships to disclose.
Clinical significance of Epstein-Barr Virus DNA load detected pre- and post-radiotherapy in nasopharyngeal carcinoma patients
Authors: X. Hou, L. Zhang, C. Zhao, L. Lu, F. Han, S. Li, P. Huang, H. Huang, Z. Guan
Journal: Journal of Clinical Oncology (2007)

10558 Background: Plasma Epstein-Barr virus DNA (EBV DNA) load has been shown to be clinically useful in the detection, monitoring, and prognostication of nasopharyngeal carcinoma (NPC). However, the clinical significance of EBV DNA load detected at different time points has not been addressed to our knowledge. In this study, we investigated whether pre- and post-treatment plasma EBV DNA load have different prognostic implications in NPC patients who were treated with radiotherapy. Methods: Plasma samples from 69 patients with primary NPC were collected before and after radiation treatment, and subjected to a real-time quantitative polymerase-chain- reaction assay of EBV DNA load. The pre-treatment primary tumor volume (GTVnx) calculated through CT images and/or MRI were documented. All patients were scheduled to follow up. Results: The pre-treatment plasma EBV DNA concentration was significantly associated with primary tumor volume (Spearman correlation coefficient=0.614; P=0.000). With a cutoff value of 20,000 copies/ml and 0 copies/ml respectively for pre-treatment and post-treatment plasma EBV DNA copy number, patients with lower EBV DNA concentrations had statistically preferable progression-free survival,metastasis-free survival and overall survival compared with those with higher EBV DNA concentrations. Cox regression analysis demonstrated that both pre-treatment EBV DNA load (P=0.050;RR=3.95) and post-treatment EBV DNA load (P=0.001;RR=11.74) were risk factors for metastasis-free survival. When further integrating pre-treatment with post-treatment concentration of EBV DNA, it was demonstrated that whether EBV DNA concentration could be dropped to 0 after treatment dominate the prognostic effect for metastasis-free survival (P=0.000). Conclusions: Pre- and post-treatment plasma EBV DNA have different clinical significance. Pre-treatment plasma EBV DNA is a reliable molecular marker reflecting primary tumor volume. While the clearance of circulating plasma EBV DNA after treatment is a good predictive marker of freedom from distant metastasis. No significant financial relationships to disclose.
Factors Related to the Incidence of Stomach Cancer in the Pittsburgh Standard Metropolitan Statistical Area 2
Authors: Trudy J. Lerer, Carol K. Redmond, Joyce Campbell
Journal: JNCI Journal of the National Cancer Institute (1977)

This report presents an analysis of several demographic discriminants of stomach cancer incidence for residents of the Pittsburgh Standard Metropolitan Statistical Area (SMSA) with the use of data collected as part of the Third National Cancer Survey, 1969-71. The Pittsburgh SMSA, one of nine areas included in the Third National Cancer Survey, was of particular interest in the study of stomach cancer, since area residents showed the highest age-adjusted incidence rate for cancer of this site while showing the fifth highest rate for all sites. To examine the data in greater detail, we used the variables of sex, race, nativity, and median income level to classify the cancer patients into homogeneous subgroups of census tracts of residence to allow comparisons of the average annual age-adjusted incidence rates among the groups. The data indicated that Pittsburgh SMSA residents showed stomach cancer incidence patterns that were generally consistent with earlier published reports; particularly when contrasted with appropriate population subgroups, higher rates appeared for males, for blacks, for lower income areas, and for areas with "large" proportions of foreign-born and foreign-stock residents. Furthermore, when one considered interactions among the factors, the relationship between ethnic composition and incidence appeared to supercede that of income among white males.
活动时胸闷-憋气-头晕-黑朦
Authors: 牛丽丽, 许玉韵
Journal: BMJ (2009)

患者男,51岁,干部,主因活动时胸闷、憋气、一过性黑矇3年,加重2个月于2008年2月入院. 患者于3年前出现活动时胸闷、气短,同时伴头晕、一过性黑矇等不适,停止活动即刻缓解,当时未予注意.于2006年曾在当地医院诊断冠心痛,按心肌缺血治疗,口服硝酸酯类等1年及对症处理(具体不详),患者症状仍时有发生,多与活动有关,平素能胜任日常活动.入院前2个月上述症状频繁出现,并较前加重,爬l层楼便觉胸闷、气短、头晕,并出现一过性黑矇,甚至晕厥,停止活动则即刻缓解。
The role of depression in couples involved in murder-suicide and homicide
Authors: M Rosenbaum
Journal: American Journal of Psychiatry (1990)

Twelve couples in cases of murder-suicide were compared to 24 couples in cases of homicide during the period 1978 to 1987 in Albuquerque, N.M. Data were obtained from police, the courts, hospital records, and interviews with friends and family of the deceased. The most striking findings were that perpetrators of murder-suicide were depressed (75%) and men (95%), while perpetrators of homicide were not depressed and one-half were women. The data indicate that the murder-suicide and homicide groups are two different populations.
Fine Structure of Hepatomas Induced in Rats With &lt;italic&gt;p&lt;/italic&gt;-Dimethylaminoazobenzene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Donald J. Svoboda, M.D.
Journal: JNCI Journal of the National Cancer Institute (1964)

The cells of malignant hepatomas induced by p-dimethylaminoazobenzene (DAB) showed many ultrastructural differences from normal liver cells, from the cells of Morris or Reuber hepatomas, and from hepatomas induced with ethionine. The deviations involved both cytoplasm and nucleus. Mitochondria, in addition to decrease in number and marked deformity of their profiles, showed large, dense, matrix granules with loss of and tubular transformation of cristae and vacuolization of matrix. The dense granules may represent an abnormality of ionic sequestration or substrate trapping as a result of deletion of mitochondrial enzymes. The wide variations in endoplasmic reticulum (ER), both in quantity and patterns assumed, indicated little correlation between ER structure and degree of malignancy. The disordered protein synthesis by these tumor cells may be related to the marked dispersion of ribosomes throughout their cytoplasm. Annulate lamellae were prominent. Cytoplasmic bodies, containing altered organelles and rich in acid phosphatase, were common in DAB-induced hepatomas. Loose and compact aggregates of fibrils, probably representing early subcellular metaplasia, were prominent in cytoplasm of many tumor cells. In nuclei, the pars amorpha was commonly present and increased in size. Interchromatinic granules and nuclear pores were present. Adenocarcinomas were composed of cells that resembled biliary epithelial cells in their ultrastructure. Moreover, the acini were bound by a basement membrane. These two observations are interpreted to indicate origin of adenocarcinomas, as well as cystic structures, from bile ducts. There were no uniform ultrastructural differences between primary and metastatic tumors.