tbuckley/cabot-search huggingface dataset:
Prognostic and therapeutic significance of pelvic lymph node dissection (PLND) extent in high-grade localized prostate cancer (PCa) patients (pts) treated with prostatectomy.
Authors: S. R. Malireddy, T. A. Masterson, R. Foster, T. Gardner, C. Sundaram, R. Bihrle, S. Beck, M. O. Koch, L. Cheng, N. M. Hahn
Journal: Journal of Clinical Oncology (2010)

e15046 Background: The practice of PLND in all PCa prostatectomy pts remains controversial. Improved prognostic accuracy with PLND is established but the therapeutic benefit is less certain. This analysis was performed to characterize the therapeutic role of PLND exclusively in high- grade PCa pts treated with prostatectomy. Methods: A retrospective review of the Indiana University prostatectomy database that contained clinical, pathologic and outcomes data on all pts undergoing prostatectomy was done. Clinically localized High-grade PCa was defined by a prostatectomy Gleason Grade total score of 8-10, absence of metastatic disease on pre-operative imaging studies. Progression Free Survival (PFS) was defined as time from surgery to post-prostatectomy PSA > 0.2, new radiographic metastases or death. Overall survival (OS) was defined as time from prostatectomy until death. Cox proportional hazards analyses were performed to identify significant prognostic clinical and pathologic patient variables that can predict PFS and OS. Results: Between 1988 and 2005, 103 pts with high-grade PCa who had bilateral PLND were identified. Demographics include: mean age 63.5; mean PSA 13.3; extracapsular extension 68.0%; seminal vesical invasion 42.7%; positive surgical margin 46.6%; stage > T3a 74.8%; mean tumor volume 6.8 ml; positive lymph nodes 13.6%; number of lymph nodes positive range 1-5; median lymph nodes resected 8 (range 2-22); any salvage therapy 55.3%. Median PFS and OS were 18.0 (95% CI 8.7 – 27.3) and 186.0 (95% CI 164.4 – 207.6) months respectively. Cox proportional hazards analyses of the above variables showed no statistically significant associations with PFS or OS. Conclusions: PLND extent failed to predict for PFS or OS in high-grade PCa pts treated with prostatectomy and bilateral PLND. Clinical stage migration leading to low frequency of lymph node positive pts, variations in the number of nodes resected and variations in dissection templates utilized are possible confounders of this analysis. Further studies are warranted in this population with an emphasis on uniform surgical techniques and pathologic analysis. No significant financial relationships to disclose.
SEER analysis of subcutaneous panniculitis-like T-cell lymphoma (SPTL)
Authors: M. G. Martin, A. F. Cashen
Journal: Journal of Clinical Oncology (2009)

e19527 Background: The uncommon nature of SPTL has hampered its clinical characterization. The EORTC described 83 cases of SPTL across 8 centers and suggested a difference in prognosis between patients with alpha/beta (AB) SPTL, who were predominantly younger (median age 36 y) and those with gamma/delta (GD) SPTL, who had a median age of 59 years (1–Blood 2008; 111: 838–45). But regional differences in the frequency of SPLT have also been suggested, with its frequency &gt;2x higher in North America than Europe (2–J Clin Oncol 2008 26: 4121–30). We hypothesized that there may be differences in the presentation between SPTL in Europe and North America. Methods: Analysis of the SEER 17 Nov 2007 (1973–2005) database was conducted with SEER Stat version 6.4.4 and GraphPad Prism 5. Cases of SPTL were defined by the ICD-O-3 code 9708. We also analyzed outcomes for patients &lt; and ≥ 50y at diagnosis. Results: 64 patients were identified with SPTL. The median age was 53y (range 2–83); 28 were &lt;50y and 36 were ≥50y. 19 (30%) patients were male, 45 were female; 44 (69%) patients were white, 13 were black and 7 were Asian. Stage was available on 27 patients: 16 (59%) were Stage I/II and 11 were stage III/IV. There was no difference in gender, ethnicity or stage distribution between those &lt; 50 and ≥ 50. Information on B symptoms was available on 20 patients, 11 (55%) of whom had B symptoms. 5-year lymphoma specific survival was 51%; 5-year OS was 41%. Median OS for patients &lt; 50 was 60 months compared to 12 months for patients ≥50 (G-B-W p=0.0183). Lymphoma specific survival was also significantly longer in the younger patients (G-B-W p=0.0015). Conclusions: In the SEER database, outcome of SPTL is strongly correlated with age. This result suggests a different biology between younger and older patients with SPTCL, possibly because the AB- subtype is more prevalent in younger patients, as reported by the EORTC. As well as differences in the overall frequency of SPTL (2), there may be geographic differences in the distribution of subtypes. [Table: see text] No significant financial relationships to disclose.
Proton beam therapy for unresectable malignancies of the nasal cavity and paranasal sinuses.
Authors: S. Zenda, R. Kohno, T. Nishio, M. Kawashima, S. Arahira, M. Tahara, R. Hayashi, T. Ogino
Journal: Journal of Clinical Oncology (2010)

e16003 Background: The curative rate of radiotherapy for unresectable malignancies of the nasal cavity and paranasal sinuses was only 10-15%. Proton beams are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery. These physical characteristics give proton beam therapy (PBT) better dose distribution than X-ray irradiation. Therefore PBT may improve treatment outcome of diseases which are located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. Methods: We reviewed 40 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses and/or the skull base; and recieved definitive PBT (>60GyE) from January 1999 to December 2006. Acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE ver. 3.0). Results: Patient characteristics were as follows: median age; 57 years (range, 22 to 84), male/female; 22/18, tumor type SCC/ACC/Olfactory neuroblastoma/ melanoma/others; 11/6/9/6/8, Induction chemotherapy yes/no; 10/30, PBT alone/PBT with concurrent CDDP; 39/1. With a median active follow- up of 45.6 months, 3-year progression-free and overall survival was 50.5% and 60.4%, respectively. The most common acute toxicities were mild dermatitis (grade 2: 32.5%), but no severe toxicity was observed (grade 3: 0%). Five patients (10%) experienced grade 3-4 late toxicities, namely cerebrospinal fluid (CSF) leakage, cataract, decreased visual acuity, central nerve-VI disorder, and bone necrosis in one patient each. One treatment-related death was reported, caused by CSF leakage grade 4 (2.5%). Conclusions: The clinical profile of PBT for unresectable malignancies of the nasal/paranasal sinuses is much better than those of radiotherapy in previous reports and seems to be sufficient to establish it as a promising treatment option for these patients. No significant financial relationships to disclose.
Abstract 141: Beneficial Effects of High-Dose Atorvastatin on Mortality and Inflammatory Responses to Severe Hemorrhagic Shock in Rats
Authors: Akihide Kurita, Takumi Taniguchi, Satoru Fujii, Koji Sato, Ken Yamamoto
Journal: Circulation (2011)

Recent studies report that the administration of statin inhibits the elevation of inflammatory cytokines such as TNF-alpha and IL-1 beta, and also inhibits the release of NO in vitro and in vivo. Moreover, several researchers claim that statin has some beneficial effects in patients with cardiogenic shock. However, there are few studies about the dose-effect relationship of statin during severe hemorrhagic shock. To evaluate the dose-effect relationship of statin in an animal model of severe hemorrhagic shock. Atorvastatin was used as a statin agent. Fifty-six male Sprague Dawley rats were used. Animals were randomly assigned to one of following four groups: Control group, no medication; High dose group, oral administration of atorvastatin (10 mg/kg/day) for 5 days; Intermediate dose group, oral administration of atorvastatin (5 mg/kg/day) for 5 days; Low dose group, oral administration of atorvastatin (2 mg/kg/day) for 5 days. Hemorrhagic shock( less than 40mmHg in systolic arterial pressure) was induced by removing blood and low arterial pressure was maintained for 40 mins. After 40 mins of shock, a half of removed blood and the same volume of Lactated Ringer9s solution were administered. No other interventions were applied during hemorrhagic shock. Hemodynamics and arterial blood gases were recorded, and plasma cytokine concentrations were measured at 2, 4, 5-hrs after hemorrhagic shock. Survival rate for the 8-hrs observation period was compared. The survival rate of High dose group at 8hrs after hemorrhagic shock was significantly higher than other groups. Removed blood volumes was significantly larger in the High dose group and Intermediate group than control group. Heart rate and blood pressure are maintained significantly higher in the high dose group than other groups. The present study showed that oral administration of high dose atorvastatin improved the survival rate after severe hemorrhagic shock in rats.
ANG1005: Results of a phase I study in patients with recurrent malignant glioma.
Authors: J. Drappatz, A. J. Brenner, S. Rosenfeld, M. D. Groves, T. Mikkelsen, D. Schiff, J. Sarantopoulos, E. Wong, P. Y. Wen, J. Castaigne
Journal: Journal of Clinical Oncology (2010)

2009
A Phase II study of VNP40101M in elderly patients (pts) with <i>de novo</i> poor risk acute myelogenous leukemia (AML)
Authors: G. J. Schiller, D. DeAngelo, N. Vey, S. Solomon, R. Stuart, V. Karsten, S. M. O'Brien, F. J. Giles
Journal: Journal of Clinical Oncology (2008)

7026 Background: VNP40101M is a novel alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links and has previously shown anti-leukemic activity in clinical trials. Methods: A confirmatory Phase II study of single agent VNP40101M was conducted in elderly pts with poor risk de novo AML. Pts received induction therapy with 600 mg/m2 VNP40101M as a single 60-minute infusion on day 1. A 2nd induction cycle could be administered to pts with a PR or hematologic improvement. Pts with CR or CRp were able to receive consolidation with araC 400mg/m2/day CIV for 5 days. Pts were eligible if they were ≥ 60 yrs and had 1 poor risk factor: age ≥ 70, ECOG PS= 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Pts with a prior diagnosis of MDS or favorable cytogenetics were excluded. Results: Enrollment was completed August 14, 2007. 85 pts were treated: median age (range): 73 (61–87); male: 59%. The majority of pts (89%) had 2 or more risk factors. The most common risk factors were age ≥ 70 (76%), pulmonary dysfunction (58%), cardiac dysfunction (48%) and unfavorable cytogenetics (48%). The response rate was 35% overall (23 CR + 7 CRp); 27% in pts with unfavorable cytogenetics, 34% in pts age ≥ 70 and 37% in pts with PS= 2. 27 responders (90%) achieved remission after 1 induction cycle. 18 responders (60%) received araC consolidation per protocol. 32 VNP40101M-related serious adverse events (SAEs) have been reported in 28 of 85 pts. The most common SAEs were related to myelosuppression or infection. Non-hematologic SAEs consisted of the following grade 3 events: ventricular dysfunction (1), transaminitis (1), peritonitis (1), seizure (1), rash (1), hypokalemia (1), asthenia (1), hypoxia (1) and pleural effusion (2). 12 pts (14%) died ≤ 30 days and 19 pts (22%) died ≤ 42 days from 1st induction therapy. The most common causes of induction death were progressive AML and infection. Health resource utilization data will be presented. Conclusions: This Phase II single-agent study of VNP40101M confirms anti-leukemic activity in elderly pts with de novo AML despite additional poor risk factors such as unfavorable cytogenetics. Severe and/or serious drug-related non-hematological toxicity is uncommon. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Vion Pharmaceuticals, Inc Vion Pharmaceuticals, Inc Vion Pharmaceuticals, Inc
THE PHARMACOLOGY OF NALORPHINE (N-ALLYLNORMORPHINE)
Authors: L.A. WOODS
Journal: Pharmacological Reviews (1956)

The pharmacological properties of nalorphine which are of greatest theoretical and practical value relate to the antagonism of the effects of morphine and morphine-related narcotics. As a result of studies with nalorphine, it has been possible to obtain new information which adds to our knowledge of the mechanisms of development of tolerance and physical dependence to morphine. Nalorphine has become the drug of choice in treating acute overdosage of morphine and related analgesics in the human. The use of nalorphine in obstetrics has made possible the use of morphine for its analgesic action without the major undesirable side-effect of fetal respiratory depression. The administration of mixtures of nalorphine and morphine (or related analgesics) for the routine production of analgesia may offer considerable therapeutic possibilities. There seems to be no doubt that such mixtures can be used which still possess very respectable analgesic effects but the reports are controversial (see V, 1) as to whether the nalorphine in these mixtures prevents the undesirable side-effects of the morphine such as sedation, respiratory depression, etc. in the human. Even though there may prove to be no antagonism of the acute untoward side-effects, if the development of tolerance and physical dependence to morphine is inhibited as has been suggested (see V, 5), the use of such mixtures for clinical analgesia would be very definitely advantageous providing a parallel increased sensitivity to the analgesic inhibitory action of nalorphine does not develop as has been shown for rats.
Phase I study of liposome entrapped paclitaxel (LEP-ETU) in patients with advanced cancer
Authors: M. N. Fishman, Y. Elsayed, N. Damjanov, J. L. Steinberg, J. J. Mahany, J. A. Nieves, S. P. Wanaski, J. L. Dul, J. W. Sherman
Journal: Journal of Clinical Oncology (2004)

2110 Background: The rationale for developing a liposomal formulation of paclitaxel is to improve the safety profile by eliminating toxicities associated with the drug formulation component, polyoxyethylated castor oil (Cremophor® EL), while maintaining or enhancing efficacy. This phase I study is designed to determine the MTD, DLT, and pharmacokinetics of LEP-ETU, an easy to use formulation of liposome entrapped paclitaxel, in patients with advanced cancers. Methods: Adult patients with incurable solid tumors receive intravenous LEP-ETU infusion over 90 minutes every 21 days until disease progression or unacceptable toxicity occurs. Dose escalation is planned with separate patient cohorts receiving 135 to 325 mg/m2 of LEP-ETU. Patients are monitored closely for any neurological changes and for tumor progression. Results: As of 16 December 2003, ten patients have received doses of 135 mg/m2 (n=3), 175 mg/m2 (n=4), or 225 mg/m2 (n=3). In the 6 men and 4 women enrolled, ages ranged from 23–80 years (median 65), and ECOG PS ranged from 0–2. Among the primary cancers were colon, breast, and pancreatic. Patients have completed up to 6 treatment cycles (median 2.5). To prevent infusion-related reactions (IRRs), patients have been premedicated on the day of infusion. In 25 of 26 such treatment cycles breakthrough IRRs have not occurred. Therefore, to assess whether premedication is clinically necessary, it is no longer required. No IRRs occurred in the single patient treated (225 mg/m2) without premedication to date. In the 225 mg/m2 cohort, 1 patient had Grade 2 neutropenia, and another had Grade 1 neuropathy, with both considered possibly related to study drug. No neutropenia or neuropathy considered related to study drug have occurred at the lower dose levels. No DLTs and no SAEs considered related to drug have been reported. Mean drug concentration versus time curves for the 135 and 175 mg/m2 cohorts parallel those reported for similar doses of paclitaxel/Cremophor EL. Conclusions: Patient accrual and dose escalation without premedication are continuing beyond the standard paclitaxel dose. At the doses administered thus far, LEP-ETU appears to be safe and well tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm, Inc.
The Metabolism of Animal Tissues Cultivated &lt;italic&gt;in Vitro&lt;/italic&gt;. I. Amino Acid Metabolism of Chick Embryonic-Heart Fibroblasts Cultivated in Synthetic Medium M 150
Authors: A E PASIEKA, H J MORTON, J F MORGAN
Journal: JNCI Journal of the National Cancer Institute (1956)

Journal Article The Metabolism of Animal Tissues Cultivated in Vitro. I. Amino Acid Metabolism of Chick Embryonic-Heart Fibroblasts Cultivated in Synthetic Medium M 150 Get access Arthur E. Pasieka, Arthur E. Pasieka Laboratory of Hygiene, Department of National Health and Welfare, Ottatva, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen J. Morton, Helen J. Morton Laboratory of Hygiene, Department of National Health and Welfare, Ottatva, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F. Morgan Joseph F. Morgan Laboratory of Hygiene, Department of National Health and Welfare, Ottatva, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 4, February 1956, Pages 995–1009, https://doi.org/10.1093/jnci/16.4.995 Published: 01 February 1956 Article history Received: 25 August 1955 Published: 01 February 1956
Abstract 9962: Carotid Intima-Media Thickness and Carotid Distensibility are Associated with Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lin Y Chen, Faye L Lopez, Rachel R Huxley, Sunil K Agarwal, Wei Pan, Aaron R Folsom, Alvaro Alonso
Journal: Circulation (2012)

Background Increased carotid intima-media thickness (cIMT) and decreased carotid distensibility are associated with an increased risk of myocardial infarction and stroke. It is unclear whether these carotid indices are associated with atrial fibrillation (AF) incidence. In the ARIC cohort, we assessed whether carotid indices are associated with an increased risk of AF and improve risk prediction of AF. Methods We included 10,077 (mean age, 56.8 ± 5.7 yrs; 56% female; 24% black) subjects who were followed from 1990-92 through 2009. cIMT, arterial diameter change (ADC), Peterson’s elastic modulus (Ep), Young’s elastic modulus (YEM), and β index were measured using carotid ultrasound in 1990-92. Incident AF cases were identified from ECGs at study exams and hospitalization discharge codes. We used multivariable Cox proportional hazards models to assess association between carotid indices and AF. Using the CHARGE AF score as the benchmark, we determined improvement in model discrimination by estimating the C statistic and calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results During follow-up (median 17.8 yrs), there were 1,028 incident AF cases. Greater levels of cIMT, Ep, and β index were significantly associated with an increased risk of AF (Table 1). The addition of cIMT and cIMT + plaque improved model discrimination marginally: C statistic (95% CI) improved from 0.795 (0.760-0.830) to 0.796 (0.761-0.831) and 0.797 (0.762-0.832), respectively. Although NRI was not statistically significant, IDI was significant for cIMT (P=0.02) and cIMT + plaque (P=0.005). Ep and β index did not improve model discrimination. Conclusions Increased cIMT and decreased carotid distensibility are associated with an increased risk of AF and modestly improve risk prediction of AF. This finding reinforces an emerging viewpoint on AF pathogenesis: AF is not purely an electrical disease, but is also a ‘vascular’ disease.
Utilizing Eastern Cooperative Oncology Group (ECOG) performance status scores to prevent harm with chemotherapy at the end of life.
Authors: Eve Newhart, Beth Karlan, Rita Shane, Vipul Patel, Bradley T. Rosen, M. William Audeh, Robert A. Figlin
Journal: Journal of Clinical Oncology (2014)

146 Background: According to ASCO’s “top five” list of non evidence-based cancer treatments and procedures, the use of chemotherapy in solid tumor patients with evidence of poor performance status is at the top of the list. The Dartmouth Atlas report revealed a significant overuse of chemotherapy at the end of life (EOL), and Cedars-Sinai was identified as an outlier with regards to this practice. Methods: Cedars-Sinai’s interdisciplinary cancer quality committee designed a new initiative to eliminate the ineffective administration of chemotherapy. Each patient’s ECOG score, entered by a nurse or physician, was used as an appropriateness screen by pharmacists before they released chemotherapy in both the outpatient and inpatient settings. If a patient did not qualify for chemotherapy based on an ECOG score of 3 or greater, the pharmacist contacted the prescribing oncologist to discuss the case. Ultimately the oncologist had the final say as to whether the patient received chemotherapy. Data was collected on ECOG scores, number of patients screened and identified as being at risk, oncologists’ responses to being notified, and whether chemotherapy was ultimately administered. Results: Available data collected on the % of orders with ECOG scores, since February of 2014 is shown in the Table. Conclusions: Data and conclusions regarding oncologists’ responses to being notified, and whether chemotherapy was ultimately administered, and harm thus prevented, is currently being compiled and will be presented at the conference. [Table: see text]
Abstract #13: Decreased expression of TCA cycle enzymes and HIF-1\#945; activation in the developing mammary gland_potential role in the higher susceptibility to carcinogens and prevention by polyphenols
Authors: Praveen Vayalil, Antonio Piras, Sreelatha Meleth, Huichen Kuo, Helen Kim, Stephen Barnes
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Rats are shown to be more susceptible to the development of mammary carcinomas when they are exposed to DMBA, during the 30-50 day-old (pubertal) period. By contrast, rats when exposed to genistein, during the early stages of mammary development (prenatal, neonatal, or pre-pubertal periods), have a reduced risk of chemical-induced mammary cancer. In the present study, we show that the abundance and activity of TCA cycle enzymes such as succinate dehydrogenase-B, fumarase and NAD+ isocitrate dehydrogenase in the mammary gland of Sprague-Dawley rats are significantly lower during puberty (day 50) compared to the prepubertal (day 21) period. Moreover, there was a subsequent activation of HIF-1\#945; in the epithelial cells of mammary gland during pubertal period. On the contrary, the abundance of these enzymes was significantly higher in resveratrol and genistein treated rats on day 50 and day 21 than the untreated control animals. These results indicate that, during puberty, the mammary gland microenvironment exists in a \#8220;pseudo-hypoxic\#8221; condition, which may potentially make it more vulnerable to tumor initiation by carcinogens. Restoration of TCA cycle enzyme levels and subsequent biochemical changes in the mammary gland may be one of the mechanisms by which dietary polyphenols reduce the risk of chemical-induced mammary cancer. Further studies will help to develop new approaches to breast cancer prevention, timely implementation of prevention strategies successfully in high-risk groups, and elucidate the mechanism of mammary carcinogenesis.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 13.