tbuckley/cabot-search huggingface dataset:
Serum c-erbB-2 ectodomain (ECD) correlates with immunohistochemical c-erbB-2 expression and predicts an aggressive clinical outcome in hormone-independent prostate cancer (HIPC) patients (pts) treated with docetaxel (D)
Authors: J. Domingo-Domenech, E. Gallardo, X. Filella, E. Fernandez, P. Fernandez, P. Gascon, B. Mellado
Journal: Journal of Clinical Oncology (2006)

4632 Background: The overexpression of c-erbB-2 has been described as a common event associated to the hormone-independent progression in prostate cancer. The clinical implications of c-erbB-2 expression in HIPC pts are not fully established. In this study we investigated the clinical significance of c-erbB-2 serum levels in HIPC pts treated with D and the correlation between serum c-erbB-2 ECD and c-erbB-2 tissue expression. Methods: Pts with HIPC treated with D were tested for serum c-erbB-2 ECD levels by immunoassay before chemotherapy. In pts with available biopsy specimens of hormone-independent tumor, c-erbB-2expression was determined by immunohistochemistry in paraffin-embedded tissue sections. PSA response to D, time to PSA progression and survival were analyzed. Results: Forty-one pts were included in the study. Median follow-up time was 23.3 (3.7–43.1) months. Median time to D progression was 4.1 (0,4–15.1) months and median survival was 11.3 (1,6–43.1). Serum c-erbB-2 correlated with PSA (r=0.351, p=0.025), inversely with time to PSA progression (r = −0.338, p = 0.033) and inversely with survival (r = −0.305, p = 0.05). Median time to PSA progression in pts with high serum c-erbB-2 (≥15 ng/ml) was 1.5 months compared to 4.6 months in pts with low levels (p = 0.0003). Survival in pts with high c-erbB-2 was 11 months and in pts with low c-erbB-2 was 15 months (p = 0.053). HIPC tissue samples from 10 pts were assessed for c-erbB-2 expression. Immunohistochemical c-erbB-2 positive staining (score +2 and +3) was detected in 4 (40%). C-erbB-2 staining showed correlation with serum c-erbB2 levels. Pts with positive staining had 19.1 ± 1.78 ng/ml and negative pts 8.8 ± 2.6 ng/ml (p = 0.001).The 4 pts with tissue c-erbB-2 overexpression had serum c-erbB-2 levels &gt;15 ng/ml, while pts with no c-erbB-2 overexpression in tissue had also low c-erbB-2 levels in serum. Conclusions: High c-erbB-2 ECD in serum is associated with a worse clinical outcome of HIPC. Our data suggest that the determination of c-erbB-2 ECD in serum translates the c-erbB-2 status in the hormone-independent tumor and may be useful to select pts for c-erbB-2-targeted therapy. No significant financial relationships to disclose.
Standard whole brain radiation (WBRT) with supplemental oxygen (O<sub>2</sub>) with or without RSR13 (efaproxiral) in patients with brain metastases originating from NSCLC: Results of a subgroup analysis
Authors: A. Nabid, J. Kresl, B. Stea, J. P. Mercier, W. Roa, I. Germain, J.-P. Bahary, L. Mechtler, J. B. Holz, J. Suh
Journal: Journal of Clinical Oncology (2004)

7115
Observations on Chemically Induced Regressing Tumors of Mouse Epidermis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jaroslav V. Frei, William F. Kingsley
Journal: JNCI Journal of the National Cancer Institute (1968)

Tumors were induced in the skin of Swiss mice by repeated applications of 7,12-dimethylbenz[a]anthracene (DMBA) (one-stage experiments) or by a single application of DMBA followed by repeated applications of enhancing agents (two-stage experiments). The rate of tumor regression, followed accurately, was lower in the one-stage than in the two-stage experiments. In the two-stage experiments, the rate of regression was proportional to the tumor yield and to the duration of the experiments. In these experiments, a shortened period of enhancement led to a marked increase in the rate of regression; the rate was also affected by the site of treatment but not by the enhancing agent. It was concluded that regressions were not due to the repeated applications of DMBA, nor to the repeated applications of enhancing agents. Since inability of the individual tumors to sustain continued growth under different experimental conditions was variable, a likely mechanism of regression of this type of tumor was the initial potential tumor focus induced by the carcinogen. Such foci had a variable potential responsiveness to nonspecific growth stimuli, based possibly in individual tumor antigens or somatic mutations, or both.
Determination of the use of CGH array to detect chromosomal instability (CIN)
Authors: J. L. Westra, L. G. Boven, J. P. De Boer, P. Van der Vlies, H. Hollema, C. H. Buys, J. T. H Plukker, K. Kok, R. M. Hofstra
Journal: Journal of Clinical Oncology (2004)

3740 Background: It is suggested that the presence of a TP53 mutation and a microsatellite stable (MSS) phenotype are associated with chromosomal instability (CIN). Further CIN phenotype appears to be associated with shorter survival (a more aggressive tumor type) compared to the microsatellite instability (MIN) phenotype. Whereas the MIN phenotype can readily be assessed by PCR with (a) set(s) of consensus markers, assessing the CIN phenotype needs much more laborious methods such as microscopic analysis of metaphases or extensive analysis of loss of heterozygosity. As an alternative we have explored the use of a subtelomeric comparative genomic hybridization (CGH) array to detect presence of chromosomal instability (CIN). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor (and normal) specimens were available from patients with stage III colon cancer adjuvantly treated with 5-fluorouracil-based chemotherapy. Tumor vs. matched normal DNA from 8 stage III colon specimens, selected for presence of TP53 mutation and a microsatellite stable phenotype, were hybridized on subtelomeric CGH arrays (n= 464 BACs). Results: Preliminary results show that 5 out of 8 analyzed MSS colon tumors with a TP53 mutation gave interpretable results. All 5 interpretable tumors showed at least 3 aberrations. Chromosomal gains on 20q were found in 4/5 specimens, on 13q in 3/5 specimens and on 8q in 2/5specimens. Conclusion: All five tumors that gave interpretable results show chromosomal abnormalities of at least 3 chromosome arms. Because of our use of subtelomeric arrays, we cannot detect interstitial gains or losses. Therefore, our results most likely represent an underestimation of aberrations present. We conclude that in principle subtelomeric CGH arrays can be used to determine a CIN phenotype. No significant financial relationships to disclose.
Abstract P055: Adverse Early Life Exposures and Carotid Atherosclerosis in Midlife: LEAP study
Authors: Charles B Eaton, Jennifer Maccani, Golareh Agha, Matthew Allison, Mary Roberts, Eric Loucks, Steve Buka
Journal: Circulation (2014)

Background: The developmental origins hypothesis suggests that adverse early life exposures predispose individuals to the development of chronic disease later in life. We tested this hypothesis by evaluating prenatal, birth, infancy and early childhood factors as predictors of midlife carotid intimal thickness and presence of atherosclerotic plaque in the carotid arteries. Methods: Participants were from the New England Family Study (N= 371), over-sampled for racial/ethnic minorities and small/large size for gestational age at birth, who had carotid IMT assessed in 2010-2011. Socioeconomic position (SEP) was prospectively measured prenatally and at age 7. Self-reported maternal pre-pregnancy BMI, birth weight, placental weight and gestational age, Growth velocity (change in weight from birth to age 4 months), BMI and blood pressure at the age 7 were measured. At midlife carotid IMT(cIMT)was measured at three angles of the far wall of the common segment for both carotid arteries; the mean of maximum measurement for these 6 segments was determined, as well as presence of plaque. Results: Of the 371 middle aged (44-51 years) participants, 56% were women and 65% were white. After adjusting for age, gender and race, robust statistically significant associations with carotid IMT and carotid plaque were found for placental weight and BMI at age 7. Socioeconomic position at age 7 was associated cIMT while the association with carotid plaque was of borderline significance. Maternal pre-pregnancy BMI and systolic blood pressure (SBP) were marginally associated with the presence of any plaque in the offspring, while cIMT was not significantly associated. Early growth velocity was marginally associated with plaque but not cIMT and birth weight was not associated with either cIMT or plaque. Conclusion: This study provides some evidence to support the developmental origins hypothesis during the prenatal period, infancy and early childhood predicting carotid atherosclerosis in mid life.
Bowel perforation and fistula formation in colorectal cancer patients treated on Eastern Cooperative Oncology Group (ECOG) studies E2200 and E3200
Authors: B. J. Giantonio, H. X. Chen, P. J. Catalano, N. J. Meropol, P. J. O'Dwyer, A. I. B. Benson
Journal: Journal of Clinical Oncology (2004)

3017 Background: The addition of bevacizumab (rhu-anti-VEGF) to frontline chemotherapy for advanced colorectal cancer (CRC) improves survival. Bowel perforation and fistula formation have been reported in colorectal cancer patients treated with bevacizumab. Methods: ECOG conducted two trials of bevacizumab in patients with metastatic CRC: as frontline chemotherapy with IFL (E2200) and second line therapy with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) (E3200). Toxicity forms and severe adverse event reports were reviewed for bowel perforation and fistula formation. Results: In E2200, 86 patients were treated. There were 2 reports of bowel perforation and 2 reports of enterocutaneous fistulae. The bowel perforations occurred in cycles 1 and 10; both occurred at anastomotic sites. One perforation occurred 27 days after hemicolectomy. The fistulae occurred in cycles 1 and 6. In E3200, 824 patients were treated (290 chemotherapy alone, 292 chemotherapy with bevacizumab, and 242 bevacizumab alone). There were 5 bowel perforations; all occurred in patients treated with bevacizumab (<1%). There were 3 fistulae, one in each arm of the study. All but one of the bowel perforations occurred in cycle 1 of therapy; one occurred in cycle 3. Three patients with perforation had invasive procedures to the gastrointestinal tract within 3 weeks of starting bevacizumab. The fistulae were noted at cycles 2, 3, and 10. Two were enterocutaneous and one was enterovaginal. All bowel perforations presented with pain: abdominal pain in 5, hip/lower extremity pain in 2, and rectal pain in one. Overall, 2 patients with perforation died of this complication. Conclusions: Use of bevacizumab in colorectal cancer patients may be associated with an increased risk of bowel perforation and fistula formation. Although an uncommon occurrence, bowel perforation should be considered in colorectal cancer patients treated with bevacizumab who develop symptoms consistent with this diagnosis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Sanofi-Synthelabo Sanofi-Synthelabo Genentech; Pfizer (Pharmacia)
Determinants of survivorship care plan implementation in U.S. cancer programs.
Authors: Sarah Birken, Deborah Mayer, Bryan Weiner, Allison Mary Deal
Journal: Journal of Clinical Oncology (2013)

78 Background: The Institute of Medicine recommended and many professional societies require survivorship care plan (SCP) use to facilitate cancer survivors’ transition from treatment to follow-up care. Rates of SCP adoption (plans to use SCPs) and implementation (current use) in US cancer programs remain unclear. Our objectives were to (1) assess rates of SCP adoption and implementation and (2) determine what distinguishes cancer programs that have implemented SCPs from those that have not moved beyond adoption. Methods: We surveyed employees knowledgeable about SCP adoption and implementation in a nationally representative sample of 100 US cancer programs. Data were analyzed using descriptive and bivariate statistics. Results: The response rate was 80%. Ninety-six percent of programs adopted SCPs, but only 45% implemented SCPs. Among programs that implemented, SCP use remains inconsistent: Use is restricted primarily to breast (81.58%) and colorectal (55.26%) cancer survivors; in 58.33% of these programs, less than a quarter of providers has ever used SCPs; and SCPs are seldom delivered to survivors or their primary care providers. Employees in many programs indicated that SCPs were adopted because of the belief that SCPs would improve care quality and the release of professional society guidelines; however, neither of these factors influenced SCP implementation. Few quality markers (e.g., NCI-designated program type; Commission on Cancer membership) influenced SCP implementation. Determinants of SCP implementation included teaching hospital program type (p = .04) and NCCCP membership (p = .009). Freestanding facility type had a negative relationship with SCP implementation (p = .02). Conclusions: Given inconclusive evidence of SCPs’ effectiveness in improving care coordination and patient outcomes, many scholars have recently advocated for research to promote SCPs’ effectiveness. These efforts may be in vain if SCPs are not more routinely implemented. Efforts should be targeted at enabling programs to implement quality improvement tools. Future research should determine what promotes SCP implementation among teaching hospitals and NCCCP members, and what inhibits freestanding facilities from implementing SCPs.
Driving Under the Influence of Alcohol, Marijuana, and Alcohol and Marijuana Combined Among Persons Aged 16–25 Years — United States, 2002–2014
Authors: Alejandro Azofeifa, Margaret E. Mattson, Rob Lyerla
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Motor vehicle accidents are the leading cause of death among youths and young adults aged 16-25 years in the United States (1). The prevalence of drinking and driving among high school students aged 16-19 years has declined by 54%, from 22.3% in 1991 to 10.3% in 2011 (2). However, the prevalence of weekend nighttime driving under the influence of marijuana (based on biochemical assays) among drivers aged ≥16 years has increased by 48%, from 8.6% in 2007 to 12.6% in 2013-2014 (3). Use of marijuana alone and in combination with alcohol has been shown to impair driving abilities (4-9). This report provides the most recent self-reported national estimates of driving under the influence of alcohol, marijuana, and alcohol and marijuana combined among persons aged 16-25 years, using data from the Substance Abuse and Mental Health Services Administration (SAMHSA) National Survey on Drug Use and Health (NSDUH) from 2002-2014. Prevalence data on driving under the influence of both substances were examined for two age groups (16-20 years and 21-25 years) and by sex and race/ethnicity. During 2002-2014, the prevalence of driving under the influence of alcohol alone significantly declined by 59% among persons aged 16-20 years (from 16.2% in 2002 to 6.6% in 2014; p<0.001) and 38% among persons 21-25 years (from 29.1% in 2002 to 18.1% in 2014; p<0.001). In addition, the prevalence of driving under the influence of alcohol and marijuana combined significantly declined by 39%, from 2.3% in 2002 to 1.4% in 2014 (p<0.001) among persons aged 16-20 years and from 3.1% in 2002 to 1.9% in 2014 (p<0.001) among persons aged 21-25 years. The prevalence of driving under the influence of marijuana alone declined 18%, from 3.8% in 2002 to 3.1% in 2014 (p = 0.05) only among persons aged 16-20 years. Effective public safety interventions,* such as minimum legal drinking age laws, prohibition of driving with any alcohol level >0 for persons aged <21 years, targeted mass media campaigns, roadside testing (e.g., sobriety checkpoints), and graduated driver licensing programs (10) have contributed to the decline in driving under the influence of alcohol in this population. These or similar interventions might be useful to prevent driving under the influence of other substances, such as marijuana alone or combined with other substances.
Disturbed pulmonary immunity and the phenotype of alveolar macrophages in bronchial asthma, gastroesophageal reflux disease and their combination
Authors: Igor Malyshev, Svetlana Lyamina, Igor Maev, Georgi Yurenev
Journal: European Respiratory Journal (2014)

The number of patients with bronchial asthma (BA), gastroesophageal reflux disease (GERD) and their combination (BA+GERD) has been growing. These diseases are associated with disturbed pulmonary immunity. We hypothesized that the disturbed pulmonary immunity in BA, GERD and BA+GERD is determined by a change in alveolar macrophage phenotype. The aim of study was to compare changes in the pulmonary immune response and alveolar macrophage phenotype in patients.

The pulmonary immune status was evaluated by levels of proinflammatory M1, antiinflammatory M2 and bivalent M1/M2 cytokines in bronchoalveolar lavage fluid. The macrophage phenotype was determined by concentrations of the same cytokines in the culture medium and by CD markers. Concentrations of cytokines and CDs were measured by flow cytofluorometry.

In BA, the phenotype of pulmonary immune response was shifted towards M2, in GERD – towards M1, and in BA+GERD – towards M2. These changes were consistent with changes in the macrophage phenotype. Each disease had a specific pattern of changes in cytokines

![Figure][1] 



and the population of alveolar macrophages was heterogeneous.

Theobtaineddataagreewiththestudy'shypothesisandsuggestthatthetherapyforinflammationinlungshouldbeadministeredwithconsiderationofspecificchangesinthecytokinepatternandphenotypicheterogeneityofmacrophages.

 [1]: pending:yes
Pattern of relapse and the risk of second malignancies in molecular subtypes of early breast cancer (BC)
Authors: B. Radecka, J. Hudala-Klecha, A. Badzio, M. Szwiec, K. Drosik, J. Jassem
Journal: Journal of Clinical Oncology (2009)

e22057 Background: In a large, consecutive series of early BC patients (pts) we investigated clinical behavior of four major molecular subtypes, with particular focus on pattern of relapse and the risk of second malignancies. Methods: BC cases were divided into four phenotypes: triple negative BC (TNBC), characterized by negativity of hormone receptors (HR) and HER2 (0–2+ by immunohistochemistry), HR+/HER2-, HR+ /HER2+ and HR-/HER2+. All pts underwent curative surgery between January 2003 and December 2007, followed by radiation and/or systemic therapy according to current standards. Univariate risks of relapse and death were estimated using Kaplan-Meier survival curves and compared with log-rank test, and the multivariate analysis used stratified Cox model. Results: Of the 783 tumors, 520, 50, 48 and 165 were classified as HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC, respectively. The TNBC and HR-/HER2+ subtypes were associated with higher tumor grade (p&lt;0.001), higher T stage (p&lt;0.001), and higher proportion of medullary type (p&lt;0.001) compared to other two subtypes. After a median follow-up of 30 months, the risk of relapse in HR+/HER2-, HR+/HER2+, HR-/HER2+ and TNBC was 5.0%, 10.0%, 12.5% and 12.1%, respectively (p=0.007). Inferior prognosis of TNBC and HR-/HER2+ types remained significant after correction by T and N stage. Of the 57 relapses, 12 were locoregional, 37 distant and 8 concomitantly locoregional and distant. In TNBC isolated locoregional relapse constituted 45% of all relapses, compared to 8.1% in three other subtypes combined (p=0.001). TNBC was associated with almost doubled risk of second malignancy compared to all other types combined (12.7% vs. 6.5%, respectively; p=0.008). This risk was significantly increased for contralateral BC and endometrial cancer (p=0.002 and 0.024, respectively). Conclusions: Poor prognosis of TNBC is related to increased occurrence of both locoregional and distant relapses. Additionally, this subtype carries increased risk of second malignancies, most likely due to higher proportion of hereditary BC. No significant financial relationships to disclose.
Abstract 215: Out-of-Hospital Cardiac Arrest Due to Drowning: Drowning Locations and Outcomes---a Nationwide Observational Study
Authors: Joo Jeong, Sang Do Shin
Journal: Circulation (2014)

Background: Little is known about the effect of drowning locations to outcomes in out-of-hospital cardiac arrest due to drowning. This study aims to describe drowning locations and associated outcomes in the South Korea. Methods: All out-of-hospital cardiac arrest patients due to drowning and treated with emergency medical services were collected from nationwide out-of-hospital cardiac arrest registry between 2008 and 2012. Main outcome was survival hospital discharge measured by hospital medical record review. Descriptive analysis using chi-square test and t-test were performed for comparing drowning locations and survival. Multivariable logistic regression analysis were performed adjusting for potential confounders to calculate adjusted odds ratios and 95% confidence intervals for determining effect size of drowning location with sport or leisure activity to the survival discharge. Results: Of 113,075 total out-of-hospital cardiac arrest patients, 1,982 patients (1.8%) were drowning victims. After exclu...
CORRECTION
Authors: N J Kenefick, C J Vaizey, A J Malouf, C S Norton, M Marshall, M A Kamm
Journal: Gut (2006)

In the Methods section, under Primers and probes and PCR assay the correct sequences should read: ''Quantitative real-time PCR was performed using the following primers: K-ras, 5'-GGCCTGCTGAAAATGA-3' (forward) and 5'-AAGGCACTCTTGCCTA-3' (reverse); FRET probe, 5'-
Plasma TIMP-1 as an independent prognostic factor in patients with gastric cancer
Authors: T. Yoshikawa, O. Kobayashi, A. Tsuburaya, H. Cho, T. Yoshida, H. Murakami, T. Osaragi, M. Sairenji, H. Motohashi
Journal: Journal of Clinical Oncology (2005)

4062 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) not only inhibits matrix metalloproteinases but also promotes cell proliferation and inhibits apoptosis. Clinically, TIMP-1 in the tumor and plasma has been reported to correlate with disease progression and prognosis in patients with various types of malignancy. Methods: To clarify the prognostic implication of plasma TIMP-1 in gastric cancer, 149 patients with primary tumors were studied preoperatively and were followed-up for more than 5 years (Median =63.0: range 60–104 months). Staging was done by UICC-TNM and plasma TIMP-1 ≥112.5 ng/mg protein were defined as positive. Results: Thirty of 149 patients had positive TIMP-1 (20.1%). Between patients with negative and positive TIMP-1, significant differences were observed in age, T, N, M, and stage of the disease. Also by univariate analysis, T, N, M, and plasma TIMP-1 were related with survival. Multivariate analysis demonstrated that T, N, and plasma TIMP-1 were significant prognosticators with hazard ratio of 2.251 (p=0.000), 1.596 (p=0.002), and 3.135(p=0.000), respectively; and in M0 tumors they were 2.640 (p=0.000), 1.532 (p=0.034), and 3.385 (p=0.002), respectively. When the survival was stratified by N category and stage, 5-year survival rates of negative and positive TIMP-1 were 94.3% (n=70) and 87.5% (n=8) in N0 (ns), 61.5% (n=30) and 0% (n=6) in N1 (p=0.000), 50% (n=10) and 0% (n=5) in N2 (p=0.031), and 22.2% (n=9) and 9.1% (n=11) in N3 (p=0.042), respectively, while those were 95.6% (n=68) and 87.5% (n=8) in stage I (ns), 75% (n=20) only for negative in stage II, 51.5% (n=17) and 0% (n=7) in stage III (p=0.003), and 21.4% (n=14) and 6.7% (n=15) in stage IV (p=0.03), respectively. Conclusions: These results suggested that plasma TIMP-1 was an independent significant prognosticator in patients with gastric cancer and would identify a more aggressive subset of the node positive and advanced disease. No significant financial relationships to disclose.