tbuckley/cabot-search huggingface dataset:
Pretherapeutic circulating endostatin levels in patients with gastric cancer
Authors: S. H. Hong, I. S. Woo, H. M. Jeon, S. Y. Rho, S. J. Koh, M. A. Lee, J. H. Byun, J. H. Kang, Y. S. Hong, K. S. Lee
Journal: Journal of Clinical Oncology (2006)

10095 Background: Endostatin is an antiangiogenic fragment of collagen XVIII and is generated by tumor-derived proteases. The functional activity of circulating endostatin is currently unknown. This is the first report on serum endostatin in gastric cancer. Methods: A total of 111 patients with gastric cancer (52 metastatic patients and 59 patients undergoing gastrectomy without distant metastasis) were included in the study. Forty eight of 52 (92%) metastatic patients received systemic chemotherapy. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA and compared with the levels in 30 healthy controls. Data were analyzed using Student’s t-test and one-way ANOVA to compare means between groups, and using Spearman rank correlation to assess correlations between clinicopathologic factors and serum endostatin and VEGF levels. Survival curves were analyzed and compared using the Kaplan-Meier method and log-rank test. Results: Mean serum endostatin and VEGF levels were higher in gastric cancer patients than in healthy controls (endostatin, 69.8 ± 16.3 vs. 52.8 ± 6.0 ng/ml [P &lt;0.001]; VEGF, 55.2 ± 7.5 vs. 31.9 ± 2.5 ng/ml [P &lt;0.001]). Endostatin and VEGF levels were significantly higher in sera from metastatic patients than in sera from patients without distant metastasis (endostatin, 79.5 ± 17.9 vs. 61.3 ± 8.2 ng/ml [P &lt;0.001]; VEGF, 57.4 ± 7.3 vs. 53.2 ± 7.2 ng/ml [P = 0.003]). There was a significant association between endostatin levels and the presence of distant metastases (r= 0.674; P &lt;0.001). A correlation was also observed between serum endostatin and VEGF levels (r= 0.718; P &lt;0.001). There was no significant difference in serum endostatin according to depth of tumor invasion, Lauren’s classification, differentiation, or regional lymph node status. A serum endostatin level higher than the median (78.14 ng/ml) was associated with a poor prognosis in metastatic gastric cancer (last follow- up at 42 months, median survival time 9 vs. 20 months [P=0.02]). Conclusions: In gastric cancer patients, serum endostatin levels are elevated and correlate with circulating VEGF levels as well as the presence of distant metastases. The endostatin level at diagnosis of metastatic gastric cancer may be useful for predicting survival time. No significant financial relationships to disclose.
An analysis of elderly patients (pts) treated on a phase III trial of cisplatin (P) plus etoposide (E) with concurrent radiotherapy (CRT) followed by docetaxel (D) vs observation (O) in pts with stage III non small cell lung cancer (NSCLC)
Authors: M. M. Sgroi, M. Neubauer, R. Ansari, R. Govindan, D. Bruetman, W. Fisher, C. Johnson, T. Breen, C. Yiannoutsos, N. Hanna
Journal: Journal of Clinical Oncology (2007)

9037 Background: Concurrent CRT is standard treatment for pts with unresectable stage III NSCLC. HOG LUN01–24 is a phase III trial testing if consolidation D improves survival following EP/XRT. Few data are available on outcomes in elderly pts. We performed a subset analysis to determine the efficacy &amp; tolerability of EP/XRT &amp; consolidation D in elderly pts (≥70 yrs) vs younger (&lt;70) pts. Methods: Patient (n=203), disease characteristics, survival &amp; toxicity were compared for pts age ≥70 (n=52) vs &lt;70 (n=151). Results: Median age for elderly was 73 vs 60 for younger pts. 34% of each group were women. Younger pts had a trend towards PS 0 (61% vs 53% elderly), FEV-1 &gt; 2 L (48% vs 43% elderly), stage IIIB disease (61% vs 53% elderly). Younger pts were more likely to be current smokers (51% vs 15% elderly). 74% of younger pts were randomized vs 67% of elderly. During EP/XRT, elderly pts were more likely to discontinue treatment due to toxicity (12% vs 2%) &amp; require hospitalization (40% vs 28%). Selected G3/4 toxicities during EP/XRT in elderly vs younger pts: neutropenia (42 vs 28%), anemia (9 vs 5%), febrile neutropenia (FN) (6 vs 11%), esophagitis (23 vs 15%), dehydration (15 vs 7%). Elderly pts were less likely to complete 3 cycles of consolidation D (76 vs 84%). Selected G 3/4 toxicities during consolidation D were similar between elderly (n=18) and younger pts (n=55), including FN (11.1 vs 10.9%). There was no difference in MST for older pts vs younger pts (17.2 vs 21.2 mos), p=0.3255. Conclusion: Chemoradiation is associated with higher rates of G 3/4 toxicities in elderly pts, including hospitalization rates. Elderly pts had lower rates of completing D, but similar incidence of D-related toxicity. There was no difference in MST between the age groups. No significant financial relationships to disclose.
Rat Neutrophils Express α4 and β1 Integrins and Bind to Vascular Cell Adhesion Molecule-1 (VCAM-1) and Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1)
Authors: Kelly L. Davenpeck, Sherry A. Sterbinsky, Bruce S. Bochner
Journal: Blood (1998)
Myeloid Leukemia of Down Syndrome: The Results of An International Retrospective Study
Authors: Marjolein Blink, Marry M. Van den Heuvel-Eibrink, Válerie de Haas, Henrik Hasle, Maureen O'Brien, Batia Stark, Julie Tandonnet, Andrea Pession, Katerina Tousovska, Daniel K.L. Cheuk, Kazuko Kudo, Takashi Taga, Jeffrey Rubnitz, Irén Haltrich, Walentyna Balwierz, Bertil Johansson, Martin Zimmermann, Dirk Reinhardt, Rob Pieters, Erik Forestier, Christian M. Zwaan
Journal: Blood (2010)
Primary retroperitoneal myxoid liposarcoma&amp;em;a non existing disease? An immunohistochemical and molecular biologic analysis
Authors: R. S. de Vreeze, D. de Jong, P. M. Nederlof, R. L. Haas, F. van Coevorden
Journal: Journal of Clinical Oncology (2008)

10569 Background: Almost all primary retroperitoneal liposarcomas are well- or de-differentiated tumors. However, occasionally primary retroperitoneal liposarcomas are diagnosed as myxoid or roundcell liposarcoma (PRMRLS), a classification based on the histologic presence of myxoid areas and a vascular crow-feet pattern, morphologically specific for myxoid/roundcell liposarcoma (MRLS). Genetically, there is a difference between MRLS and well- or de-differentiated liposarcoma. MRLS have a classical translocation causing FUS-CHOP or EWS-CHOP fusion while well- or de-differentiated liposarcomas are characterized by amplification of the 12q13–15 region, which among many other genes includes MDM2 and CDK4. Since in particular all MRLS are highly radio- and chemo-sensitive, differentiation between subtypes is important to indicate prognosis and optimize treatment. We studied whether PRMRLS are related to true MRLS or should be classified as well- or de-differentiated liposarcomas with focal MRLS-like changes. Methods: Patients classified as PRMRLS (n=16) were reviewed. Results were compared to a group diagnosed with primary extremity MRLS (n=20). In both groups, histopathologic, immunohistochemical and molecular biologic analysis was performed. Results: In PRMRLS, MDM2 and CDK4 stained slides were positive in 65% and 80% respectively and both tests were negative in all extremity MRLS. Translocation analysis showed FUS-CHOP or EWS-CHOP fusion to be present in all extremity MRLS, but absent in all sixteen investigated PRMRLS. Multiplex Ligation-Dependant Probe Amplification showed amplification of region 12q13–15 in 94% of PRMLS and in 5% of primary extremity MRLS patients. Conclusions: Classic MRLS, characterized by a FUS-CHOP or EWS- CHOP fusion oncogen was not found in PRMRLS, while MDM2 and CDK4 amplification was present in most specimens. In PRMRLS, the probability of focal MRLS-like changes in well- or de-differentiated liposarcoma is a more presumable explanation for the histologic appearance. In these cases most likely treatment should be designed as for well- or de-differentiated liposarcoma. No significant financial relationships to disclose.
Abstract P117: County Level Cardiovascular Health in the United States
Authors: Courtney S Pilkerton, Thomas K Bias, Stephanie J Frisbee
Journal: Circulation (2014)

Background: Cardiovascular disease is the leading cause of death in the United States, so improving cardiovascular health (CVH) is a key population health goal. As part of public health efforts to achieve this, the American Heart Association recently developed a comprehensive CVH metric that incorporates smoking, body mass index, physical activity, diet, cholesterol, blood pressure, and blood glucose. The objectives of the current study were to measure CVH in all US counties and identify key socioeconomic determinants of county-level CVH. Methods: Data from the Behavioral Risk Factor Surveillance System were used to determine calculate CVH for each county in 2009. Federal Information Processing Standards codes were used to obtain scores for counties with a sample size of 15 or more; 62% (1948 of 3142) of United States counties had available data . The main outcomes were age-standardized mean CVH score and percentage of poor or ideal health. Data on county-level socioeconomic indicators were abstracted from the Area Resource File. Results and Conclusions: Overall, 18% of the population had poor CVH, 77% had intermediate, and 5% had ideal. Between counties the average overall CVH varied from 2.13 to 4.80, the percentage of ideal health varied from 0% to 46%, and the percentage of poor health varied from 1% to 76%. Counties with the poorest health were in the Midwest and Southern regions. There is a moderate positive relationship between mean CVH and per capita income (r=0.355) and a weak positive relationship between mean CVH and percent urban population (r=0.245). In conclusion, there are few counties with a substantial percentage of their population with ideal health, there is a wide range of cardiovascular health status within the United States, and there is some association of increasing CVH with increasing income and urbanization.
Effect of interval between diagnosis of advanced cancer and cessation of active anti-cancer treatment on survival in terminally ill cancer patients
Authors: Y. Kim, J. Lee, W. Choi, J. Park, H. Kim, S. Lee, D. Kim, J. Lee, Y. Bang, D. S. Heo
Journal: Journal of Clinical Oncology (2009)

e20630 Background: Although various prognostic factors have been proposed to predict survival in terminally ill cancer patients, accurate prognostication is still a challenging task for oncologists. The objective of this study was to evaluate whether the time interval between diagnosis of advanced cancer and cessation of active anti-cancer treatment (ATP; active treatment period) can predict survival in terminally ill cancer patients. Methods: We prospectively evaluated 79 patients with advanced (recurrent or metastatic) cancer who were determined as terminal stage, namely cessation of active anti-cancer treatment and transition to palliative care, by attending oncologists. ATP and other known prognostic factors including clinical symptoms and signs, performance status, laboratory tests, and clinical prediction of survival (CPS) were analyzed. Results: Of the 79 patients, 46 were male (58%) and 33 were female (42%) with a median age of 60 years (range, 21–82). Median overall survival after being diagnosed with advanced cancer was 11.6 months (95% confidence interval (CI), 8.02–15.18), and survival after being determined as terminal stage was 1.9 months (95% CI, 1.38–2.42). According to 3 ATP categories (&lt; 3months, 3–12 months, and &gt;12 months), terminal stage survival were 1.0 month, 1.8 months, and 3.6 months, respectively (p=0.002). On multivariate analysis, short ATP, non-colorectal cancer, fatigue, and Karnofsky performance status less than 50 were significantly associated with a poor prognosis. Conclusions: Our study suggests that ATP is an independent prognostic factor for survival in terminally ill cancer patients who cannot receive active anti-cancer treatment anymore. Future prognostic models should include ATP as a prognostic variable. No significant financial relationships to disclose.
Role of chemoradiation in uresectable Gall bladder carcinoma: 5 years retrospective analysis of RIMS
Authors: I. Y. Singh, T. T. Singh, J. L. Singh
Journal: Journal of Clinical Oncology (2008)

15650 The incidence of Cancer gall bladder (Ca GB) is increasing globally and in India it is concentrated in the Ca GB belt area which includes the valley of Manipur. Though surgery is potentially curative, majority are detected in advanced unresectabale stage. Radical surgery carries a high mortality and morbidity rate along with high local recurrence rate. Hence the outcome of this disease remains dismally poor. Radiotheapy is beneficial for treatment of post surgical micro residual disease only. The role of chemotherapy is not clearly defined. It has not shown to be effective either as primary or as adjuvant therapy in any large randomized trials conducted so far. Though newer effective chemotherapeutic agents have emerged during the last decade none has shown to be effective to be recommended as standard one. In our Radiotherapy department of (Regional Institute of Medical sciences) RIMS, Imphal various chemotherapeutic protocols with or without RT were being tried during the last 5 years. A retrospective analysis of 60 cases was done to find out whether really there is any beneficial role of chemotherapy/chemo-radiation in advanced nonresected Ca GB. And if at all which one is the most promising one? Analysis of various regimens by grouping into subsets were done with overall survival as the primary end point. Capecitabine, gemcitabine oxaliplatin, cisplatin/carbopatin with 5- F.U. continuous infusion were tried and all have shown to be effective. However Oral capcitabine included regimens has shown to have the best survival benefit. The mean average survival of capcetabine included regimen was 2.6 years in the subset analysed. Whereas other regimens showed mean average survival of 8 months to 16 months. Those subset of patients who received only best supportive care had 3.6 months of mean average survival. Though the study population is small the results indicates that the newer chemotherapeutic agents namely capecitabone, Gemcitabine and platinum analogues has beneficial effect in prolonging survival with tolerable toxicity. No significant financial relationships to disclose.
The impact of leukocytosis on survival, leukemic transformation, and thrombosis in polycythemia vera
Authors: N. Gangat, J. Strand, C. Y. Li, A. Pardanani, R. Mesa, A. Tefferi
Journal: Journal of Clinical Oncology (2007)

7029 Background: A leukocyte count of &gt; 15 ×10 9 /L has recently been associated with myocardial infarction in polycythemia vera (PV). In the current study, we examine the impact of such degree of leukocytosis on survival, leukemic transformation (LT), and thrombosis in a large cohort of PV patients from a single institution Methods: Data was abstracted from the medical records of a consecutive cohort of patients with PV defined by the World Health Organization criteria. Results: i. Patient characteristics The study cohort included 459 patients (median age, 60 years). Median follow-up was 64 months. ii. Survival In a multivariable analysis, advanced age, leukocyte count of = 15 × 10 9 /L, and arterial thrombosis at diagnosis were significantly associated with inferior survival. A prognostic model based on age = 60 years and leukocyte count = 15 × 10 9 /L separated low-risk, intermediate-risk, and high-risk patient groups with respective median survivals of 272, 162, and 108 months (p&lt;0.0001). iii. Leukemic transformation In a multivariable analysis, only leukocyte count was significantly associated with LT; median leukemia-free survival for patients with leukocyte count = 15 × 10 9 /L was 273 months vs. not reached for those with lower leukocyte count (p&lt;0.0001). iv. Thrombosis at diagnosis In multivariable analysis, arterial thrombosis at diagnosis was significantly associated with previous history of arterial thrombosis, hypertension, and tobacco use; venous thrombosis at diagnosis was significantly associated with previous venous event and splenomegaly. v. Thrombosis during follow- up In multivariable analysis, arterial thrombosis during follow-up was significantly associated with previous arterial event, hypertension, and tobacco use; venous thrombosis during follow-up was significantly associated with previous venous event, diabetes mellitus, advanced age, and leukocyte count = 1,500 × 10 9 /L. Conclusions: The current study for the first time identifies leukocytosis as a risk factor for inferior survival, LT risk, and venous thrombosis in PV. No significant financial relationships to disclose.
Mechanisms contributing to renal resistance to atrial natriuretic peptide in rats with common bile-duct ligation.
Authors: X Ni, Y Cheng, L Cao, D G Gardner, M H Humphreys
Journal: Journal of the American Society of Nephrology (1996)

Blunted volume expansion (VE) natriuresis and renal resistance to atrial natriuretic peptide (ANP) characterize states of pathological sodium retention. This study examined rats 1 to 3 wk after common bile-duct ligation (CBDL), at which time they had hyperbilirubinemia and hypoalbuminemia. Sham-operated normal rats (Sham) showed an increased sodium excretion rate (UNaV) from 1.0 +/- 0.1 to 16.3 +/- 3.9 muEq/min in response to acute VE (iv saline, 2 mL/100 g body wt over 5 min), whereas CBDL rats had a blunted response that was apparent after 1 wk and became maximal at 2 and 3 wk (0.3 +/- 0.1 to 3.2 +/- 0.4 muEq/min at 3 wk, P < 0.01 versus Sham response). The peak urinary cGMP excretion rate (UcGMPV) was also blunted (37.9 +/- 3.6 versus 87.5 +/- 8.3 pmol/min, P < 0.01) despite an even greater increase in plasma ANP concentration (Sham, 9.6 +/- 0.4 pg/mL in hydropenia to 22.8 +/- 2.6 pg/mL after VE; CBDL, 15.3 +/- 2.3 to 41.8 +/- 6.8 pg/mL). ANP-dependent cGMP accumulation by isolated inner medullary collecting duct (IMCD) cells from both Sham and CBDL rat kidneys was dose-dependent; however, at higher concentrations of ANP (> 10(-8) M), accumulation by cells from CBDL rats was significantly blunted, indicating resistance to ANP. Binding of 125I-ANP to IMCD cells was not different in CBDL rats compared with Sham control rats. Renal denervation improved but did not completely reverse the blunted natriuresis, and ANP resistance persisted in IMCD cells from denervated kidneys of CBDL rats. Incubation of IMCD cells with the phosphodiesterase inhibitors isomethylbutylxanthine or Zaprinast (each at 10(-3) M) restored ANP responsiveness in both innervated and denervated kidneys from CBDL rats, and intrarenal infusion of Zaprinast (10 micrograms/min) corrected the blunted increase in UNaV and UcGMPV after VE in rats with CBDL. These results suggest that ANP resistance in a model of abnormal sodium metabolism devoid of intrinsic renal disease may be related to increased activity of phosphodiesterase in renal target cells for ANP as well as to heightened renal nerve activity.
Protein multiplex sandwich immunoassay: A reliable and objective method for complete molecular characterization of breast cancer from core needle biopsies
Authors: G. Sauer, N. Schneiderhahn-Marra, M. Bãuerle, C. Kurzeder, K. Koretz, R. Kreienberg, T. Jost, H. Deissler
Journal: Journal of Clinical Oncology (2006)

20025 Background: Within the last years, protein microarrays have been developed to quantify a large number of parameters present in a given sample simultaneously. Such miniaturised and parallelised sandwich immunoassays are of general interest for all proteomic and diagnostic approaches in which several parameters have to be determined from small samples. We describe the development of a bead-based flow cytometry that represents a convenient approach for rapid multiplex detection of functional target molecules from breast cancer biopsies. Methods: Briefly, sonographically guided core needle biopsies (CNB) were performed from 120 breast cancer masses from different patients. All biopsies were carried out with an automated core biopsy device fitted with 14-gauge (22 mm excursion) needles. Tumor samples were frozen on at −70 Celsius and pulverized. Proteins were extracted, allowing the simultaneous quantification of more than hundred proteins by a bead-based multiplex sandwich immunoassay. Results: The total amount of extracted protein from tumor tissues (mean weight of 20 mg) ranged from 300 to 1000 μg. We demonstrate appropriate sensitivity, reproducibility, and robustness for this protein microarray technology to characterize clinical samples and generate reliable data sets. A set of multiplexed sandwich immunoassays based on Luminex beads were developed that identify marker proteins indicative of prognosis or response to therapeutic options. Up to almost hundred parameters were identified and quantified simultaneously of which estrogen, progesterone and HER2 status in the multiplex assay was highly significant correlated to results obtained by immunohistochemistry (IHC) (p &lt; 0.01). Conclusions: Our results demonstrate that this new bead-based protein microarray technology rapidly and reliably characterizes tissue samples to generate data sets of molecular marker. Therefore, this technology may once replace traditional IHC in determining marker proteins indicative of prognosis or response to therapeutic options. No significant financial relationships to disclose.
Molecular correlates associated with a phase II study of temsirolimus (CCI-779) in patients with metastatic or recurrent endometrial cancer—NCIC IND 160
Authors: A. M. Oza, L. Elit, J. Biagi, W. Chapman, M. Tsao, D. Hedley, C. Hansen, J. Dancey, E. Eisenhauer
Journal: Journal of Clinical Oncology (2006)

3003 Background: PTEN is a tumor suppressor gene and mutations in PTEN causing loss of protein expression/function may play a significant role in the pathogenesis of EC. Loss of PTEN protein expression has been reported in 26–80% of EC and leads to deregulated PI3K/Akt/mTOR signalling which may give neoplastic cells a survival advantage by enhancing angiogenesis, protein translation and cell cycle progression. Inhibition of mTOR, a protein kinase downstream of the PI3K/Akt pathway and target of rapamycins, inhibits proliferation of EC cell lines and formation of EC in PTEN−/+ heterozygous mice. We have evaluated temsirolimus (T) an ester derivative of rapamycin that inhibits mTOR given the frequent loss of PTEN in human EC. Methods: A two stage, phase II study has been conducted to evaluate single agent activity of T in women with recurrent or metastatic EC (chemotherapy naïve, upto 1 prior line of hormonal therapy). Treatment was 25mg i.v. weekly. One cycle is defined as 4 weeks of therapy. Thirty one patients (pts) have been registered; 23 are evaluable for toxicity and 19 for response. Results: Preliminary results have demonstrated encouraging activity and the trial fulfilled predefined criteria for activity. Of 19 pts evaluable for response, 5 have had a confirmed partial response (PR) (26%) and 12 have stable disease (SD) as best response (63%). Two pts had progressive disease (PD) (11%). PTEN, phosphorylated (p) mTOR and p-S6 protein (immunohistochemistry) results are available on 9 pts to date. The preliminary results indicate that responses and stable disease are seen in pts irrespective of PTEN status. Loss of p-mTOR was evident in tumor cells from all pts (range 75–99% loss) and did not correlate with response. Phosphorylated S6 was low in tumor cells in the one pt who had PD (5%), and levels were higher in pts with PR and SD (mean and median 30%). Conclusions: We conclude that Temsirolimus has encouraging single agent activity for in recurrent and metastatic EC, and the findings indicate this is irrespective of PTEN status. We are currently evaluating activity of T in pts previously treated with chemotherapy and molecular correlates in additional specimens. No significant financial relationships to disclose.