tbuckley/cabot-search huggingface dataset:
Breast tumor morphometry in relation to race reveals significant differences among Nigerians, African-Americans and Caucasian Americans
Authors: F. O. Ikpatt, J. J. Dignam, A. Khramtsov, T. Grushko, J. Fackenthal, L. Sveen, R. Nanda, R. Ndoma-Egba, O. I. Olopade
Journal: Journal of Clinical Oncology (2004)

9567 Background: African American (AA) women have a lower risk of breast cancer (BC) than Caucasian(C) women, but tumors in AAs are more likely to be poorly differentiated and estrogen receptor negative, leading to worse outcomes. In West Africa, the founder population of most AAs, BC is considered a rare virulent disease of young women. Thus, comparative analysis of BC in AA and Nigerian (N) populations could reveal shared genetic components of the disease. Methods: The cases were randomly selected from the tumor banks at the Universities of Chicago and Calabar (Nigeria). H&E stained slides from 148 N, 166 AA and 170 C cases were evaluated for volume corrected mitotic index (smi) expressed as mitosis/mm2, mean nuclear area (mna) aided by a digitizing interactive video overlay, and fraction of fields with tubular differentiation (ftd). Empirical distributions of and inter-relationships between the three features were examined, followed by comparisons of each feature between groups according to country of origin of the sample. Results: All morphometric features considered individually were highly associated with tumor grade and discriminant analysis indicated ftd was the most effective single variable for correctly classifying tumor grade followed by smi and mna. Mean values were significantly different among the three groups (p<.0001). The sma and mna values were largest for N, intermediate for AA, and lowest for C (smi N=26.5±14.7, AA=19.9±6.7, C=14.5±5.1; mna N=55.9±19.9, AA=47.1±12.7, C=34.3±10.3). For smi and mna, all pair wise means differed (p<0.05). The pattern was reversed for ftd, with the N cases having the smallest value (ftd N=17.8±17.0, AA=21.9±16.6, C=28.4±17.9). Conclusions: Significant differences in proliferative activity and degree of differentiation among N, AA, and C BCs exist, even after adjusting for other confounding variables like age and stage. These differences are likely genetically programmed but may be masked by genetic admixture among AA. Future work will evaluate the molecular determinants of tumor morphometry and whether these differences contribute to disparities in health outcomes. No significant financial relationships to disclose.
Cancer in Families With Severe Combined Immune Deficiency&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D Morrell, C L Chase, M Swift
Journal: JNCI Journal of the National Cancer Institute (1987)

Cancer incidence and mortality were analyzed in 1,181 blood relatives and 558 spouse controls in 24 families of severe combined immune deficiency (SCID) patients, to test the hypothesis that heterozygous carriers of a gene for an autosomal recessive form of SCID are predisposed to cancer. Since at least 1 patient in each family was female and there were no cases outside the probands' sibships, the pattern of occurrence of SCID within the families was compatible with autosomal recessive inheritance. The observed numbers of cancer cases and deaths did not exceed the expected numbers derived from population-based rates; and there was no cancer excess when incidence rates in blood relatives were compared directly to those in spouse controls, since the rate ratios were 1.2 and 1.0 for males and females, respectively. In addition, cancer rate ratios were not significantly elevated when calculated separately for the 9 families of adenosine deaminase (ADA)-deficient SCID patients and for the 15 families without evidence of ADA deficiency.
Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study
Authors: David Tougeron, Guillaume Mouillet, Isabelle Trouilloud, Thierry Lecomte, Romain Coriat, Thomas Aparicio, Gaetan Des Guetz, Cédric Lécaille, Pascal Artru, Gaelle Sickersen, Estelle Cauchin, David Sefrioui, Tarek Boussaha, Aurélie Ferru, Tamara Matysiak-Budnik, Christine Silvain, Lucie Karayan-Tapon, Jean-Christophe Pagès, Dewi Vernerey, Franck Bonnetain, Pierre Michel, Julien Taïeb, Aziz Zaanan
Journal: JNCI Journal of the National Cancer Institute (2016)

Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients.This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided.A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02).This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC.
Heteroplasmy and polymorphism in the major noncoding region of mitochondrial DNA in Japanese monkeys: association with tandemly repeated sequences.
Authors: K Hayasaka, T Ishida, S Horai
Journal: Molecular Biology and Evolution (1991)

We have sequenced the major noncoding region of mitochondrial DNA (mtDNA) of four Japanese monkeys and have found length polymorphism in the sequenced region. The length polymorphism resulted from two tandem duplications of 160-bp sequences which contained the conserved sequence blocks 2 and 3 and the light-strand transcription-promoter region. We also found polymorphisms in this mtDNA region among 100 Japanese monkeys from 12 localities, 90 of which were analyzed using DNA amplified through the polymerase chain reaction. In two localities, we found individuals with heteroplasmic mtDNA which had different numbers of the 160-bp repeats mentioned above. The 100 samples were classified into six types in terms of length and presence/absence of the recognition site of two restriction enzymes in the major noncoding region.
Domestic use of hypochlorite bleach and respiratory infections in children
Authors: Jan-Paul Zock, Lídia Casas, Alícia Borràs-Santos, José Jacobs, Esmeralda Krop, Dick Heederik, Anne Hyvärinen, Martin Täubel
Journal: European Respiratory Journal (2011)

Hypochlorite bleach is commonly used in private homes for cleaning and disinfection. Professional bleach use has been associated with respiratory symptoms in adults, and a small study from Belgium suggested that domestic bleach use may increase the risk of recurrent respiratory infections in children (Nickmilder, M., et al. Pediatr Allergy Immunol 2007; 18:27-35). We studied the relationship between domestic bleach use and respiratory infections in a large international study of school children. Parent-administered questionnaires were obtained from 9425 children aged 6-12 years from 54 primary schools in Finland, The Netherlands and Spain. Information was obtained on the use of bleach for home cleaning and respiratory health including 8 types of infections in the previous 12 months. The use of bleach at least once a week was more common in Spain (72%) and The Netherlands (57%) than in Finland (7%). In multivariable logistic regression models with adjustment for sex, age, educational level, passive smoking, presence of mould in the home and country, the risk of several respiratory infections was higher in children who lived in a home where bleach was used. This association was particularly apparent for influenza (Odds Ratio 1.21; 95% Confidence Interval 1.06-1.37), tonsillitis (1.20; 1.03-1.39) and bronchitis (1.16; 0.95-1.42). The risk of any recurrent infections apart from common colds in the previous year (overall 53%) was 14% higher in children from homes where bleach was used, being consistent for the 3 countries (p for heterogeneity 0.57). In conclusion, this large cross-sectional study confirms that the use of bleach in the home may increase the risk of respiratory infections in children.
Immunohistochemical subgroups in diffuse large B-cell lymphoma: Clinicopathologic study of 62 cases from Perú.
Authors: S. M. Quintana Truyenque, C. Barrionuevo, C. A. Samanez, T. Vidaurre, R. Mantilla, L. Casanova
Journal: Journal of Clinical Oncology (2010)

e18543 Background: Recent studies have shown that diffuse large B- cell lymphoma (DLBCL) cases with gene expression profiles of germinal centre B-like (GCB) had a better prognosis than DLBCL cases with gene expression profiles of activated B cells (non-GCB). DLBCL can be classified into three immunohistochemical (IHC) subgroups: GCB expressing CD10 and/or Bcl6 but not MUM1; activated GCB expressing at least one of GC B-cell markers and MUM1; and activated non-GCB expressing MUM1 but not GC B cell markers. Purpose: To determine the frequency of these patterns and the association with the clinical features, International Prognostic Index (IPI), clinical stage (CE), and treatment response. Methods: IHC analysis on paraffin-embedded tissues was performed using the streptavidin-avidin- biotin method in 62 cases of DLBCL. The IHC expression was performed as follows: positive (>30% of cells), and negative (≤30% of cells). Results: The male/female ratio was 1.2/1. The mean age was 58.6 (range: 22 - 89). 64.5%. Patients presented with nodal disease (n=40) and extranodal disease (n=22), CE I-II (n=35), CE III-IV (n=27), ECOG 0-1 (n=34), ECOG 2-4 (n=28), IPI BR-IB (n=37), and IPI IA-AR (n=25). 6 cases, 12 cases and 40 cases corresponded to GCB, activated GCB, and activated non-GCB patterns, respectively. There were 4 cases not evaluable. There was significant association between CE I-II and GCB subgroups as well as between CE III-IV and activated non-GCB subgroup (p< 0.05). Mean course of CHOP was 4.7. There was significant association between treatment response and CE (p<0.05), ECOG (p=0.009), and IPI (p=0,002) but not dependent of the patterns (p=0.746). The 3-year Overall survival (OS) for GCB subgroups and activated non-GCB subgroup was 67.9% and 60.3% respectively. The 3-year event-free survival (EFS) for these subgroups was 64.6% and 55.9%. Conclusions: The activated non-CGB was the most frequent IHC subgroup. Early CEs were associated with the GCB patterns. In our cases the IHC subgroups does not correlate with IPI and treatment response. No significant financial relationships to disclose.
Abstract 215: First Shock Success Rates Across Waveforms and Energy Levels in Adult Cardiac Arrest: A Systematic Review and Meta-analysis
Authors: Laurie J Morrison, Rowan Henry, Vivien Ku, Jerry P Nolan, Peter T Morley, Charles D Deakin
Journal: Circulation (2012)

Objectives: Current guidelines advise a single biphasic shock followed by chest compressions; however, it is unclear if this applies to all waveforms and energy levels. We conducted a systematic review and meta-analysis of the literature to determine the comparative success rates for single-shock defibrillation across waveforms evaluated in out-of-hospital cardiac arrest patients presenting in Ventricular Fibrillation. Methods: A comprehensive search strategy was used across Embase, Medline, Cochrane libraries, dissertation abstracts and clinicaltrials.gov, and unpublished data was sought. Two investigators independently reviewed titles, abstracts and full texts in a hierarchical manner for study eligibility with a quadratic kappa score at each level. Two authors abstracted data independently, and the quality of the articles was assessed using the Jadad scale. Outcomes were termination of fibrillation to any rhythm (TOF), return of organized rhythm (ROOR) and return of spontaneous circulation (ROSC). Results: A total of 3,281 potentially relevant citations were identified and of these 7 RCTs were selected with Kappa values of titles 0.53, abstract 0.71, and article 0.94. Mean quality scores varied from 1-2.5/3. First-biphasic shock success (pooled mean) for TOF were similar: Biphasic Truncated Exponential (BTE) 200J 90.5%, BTE 150J 89.9%, Rectilinear Biphasic (RLB) 120J 84.9% but were lower and divergent for both ROOR BTE 200J 43%, BTE 150J 38%, RLB 23% and ROSC; BTE 200J 39%, BTE 150J 78%, RLB 46%. Median time to first shock (min) varied across trials (5.1 BTE 200/150J, 10.4 RLB) and may contribute to observed differences. Conclusion: First shock success rates as measured by the industry standard of TOF do not significantly differ across biphasic waveforms and energy levels.
Effect of adjuvant zoledronic acid (ZOL) on disseminated tumor cells (DTC) in the bone marrow (BM) of women with early-stage breast cancer (ESBC): Updated results.
Authors: S. Greenberg, J. W. Park, M. E. Melisko, A. Goga, M. M. Moasser, M. Anderson, J. H. Scott, L. A. Petrillo, D. H. Moore, H. S. Rugo
Journal: Journal of Clinical Oncology (2010)

1002 Background: DTC are associated with increased risk of distant recurrence and death in patients (pts) with ESBC, especially if present after adjuvant chemotherapy (AT). Bisphosphonates (BP) including clodronate and ZOL have demonstrated anti-tumor activity in several clinical trials. We designed a pilot study to evaluate the effect of ZOL on DTC in pts with ESBC and DTC following AT. We hypothesized that ZOL would reduce DTC which could serve as a surrogate marker of anti-tumor effect. Methods: Pts with stage I-III BC were evaluated for DTC with a unilateral BM aspiration after neoadjuvant or AT. Eligibility was defined as > 4 DTC/mL w/in 12 wks of study entry, defined as > 2.5 standard deviations above that found in 50 normal BMs (Park, Proc ASCO 2002). Pts received 4 mg of ZOL IV monthly for 24 months (mos). Concomitant hormonal therapy was allowed. Serum creatinine (Cr) and toxicity were evaluated monthly, urinary n-telopeptide (nTX) was measured at 0, 2, 4, 6, 12, and 24 mos, peripheral blood circulating tumor cells (pbCTC) were measured every 6 mos. Repeat BM aspirations were performed at 12 and 24 mos. DTCs were detected by immunomagnetic enrichment + flow cytometry (FC): 4 mL of BM aspirate was subjected to anti-EpCAM-conjugated iron particles, followed by FC for EpCAM, CD45, and nucleic acid content for quantitative analysis of DTC/mL. Results: 45 pts were enrolled. Median FU is 49 mos (5-81 mo). Median DTC at baseline were 13.3 DTC/mL (range 4-333). DTC increased with tumor size up to 5 cm (p < 0.001). There was a significant reduction in DTC from baseline to 12 mos (mean reduction 9.3, range: 23.6 to 57.2, p > 0.0001), and from baseline to 24 mos (p < 0.001). Baseline DTC predicted recurrence (p > 0.0002); there was a trend towards greater risk of recurrence in pts with higher baseline pbCTC (p > 0.09). ZOL was well tolerated; 1 pt withdrew due to minor toxicity and there was 1 dose delay for elevated Cr. Conclusions: Adjuvant ZOL results in a reduction in DTC at 12 and 24 mos in pts with high risk ESBC; treatment was well tolerated. Elevated DTC following AT was predictive of recurrence. DTC may be a surrogate marker of the antitumor effect of ZOL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Foundation Novartis Novartis
Prematurity and use of asthma medication from childhood to young adulthood
Authors: Anne Louise Damgaard, Bo MÃ¸lholm Hansen, RenÃ© Mathiasen, Frederik Buchvald, Theis Lange, Gorm Greisen
Journal: European Respiratory Journal (2013)

Introduction 

Preterm birth is associated with increased risk of asthmatic symptoms in childhood, but it is not clear whether this association persists into adulthood.

Aims and objectives 

We aimed to investigate the association between gestational age (GA), neonatal respiratory morbidity (acute and bronchopulmonary dysplasia) and the use of prescription asthma medication from infancy to young adulthood.

Methods 

This is a register study of a Danish cohort of all infants born 1980-2009. Use of asthma medication (combination of inhaled β-2 agonists and at least two retrievals of other drugs for obstructive airway disease) was evaluated in 2010-2011. Multivariate logistic regression was used to evaluate associations.

Results 

Data were obtained on 1790241 individuals, 84.6% of all infants born in the period. There was a strong dose-response association between GA and asthma medication during infancy with odds-ratios (OR) (95% CI): 3.87 (2.47-6.07) in GA 23-27 weeks, 2.34 (1.82-3.01) in GA 28-31 weeks and 1.59 (1.43-1.77) compared to GA 37-42 weeks. This association weakened gradually with increasing age and was not statistically significant in 25-31 year olds. The association was only partly explained by neonatal respiratory morbidity.

Conclusion 

There was an association between gestational age per se and the use of prescription asthma medication in infancy and childhood, which appeared to weaken during adolescence and early adulthood. It remains to be investigated whether the strength of this association will increase again later in adulthood.
Increased Growth of Tumor Isotransplants After Immunosuppression of the Recipient Mice by Methotrexate or 5-Fluoro-2′-Deoxyuridine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Julius Reiner, Chester M. Southam
Journal: JNCI Journal of the National Cancer Institute (1967)

Immunosuppression of a graft recipient by chemotherapy or irradiation delays rejection of homotransplants in animals and man. If such immunosuppression were shown to similarly influence the growth of syngeneic tumors (isctransplants), it would provide another kind of evidence that tumor tissue is antigenically different from normal host tissues and that host immunologic mechanisms react against these antigenic differences to inhibit tumor growth. This concept was tested by quantitative transplantation of syngeneic tumors in immunosuppressed mice. Fibrosarcomas were induced in C57BL/6 mice by a single intramuscular injection of methylcholanthrene. Primary syngeneic transplants, with the use of cell suspensions, were made into mice given Methotrexate (MTX) or 5-fluoro-2′-deoxyuridine (FUDR) and into normal recipients. Various forms of treatment of the recipients with MTX or FUDR resulted in a higher percentage of takes than occurred in untreated control recipients.
Abstract 11927: MRI T1 Mapping of the Right Ventricle Using High Resolution ANGIE
Authors: Bhairav B Mehta, Xiao Chen, Michael Salerno, Christopher M Kramer, Kenneth C Bilchick, Frederick H Epstein
Journal: Circulation (2013)

Introduction: MRI T1 mapping has become an important method for the quantitative assessment of left ventricular myocardial fibrosis. T1 mapping of the right ventricle (RV) would also be valuable, h...
Identification of patients who most benefit from hepatic arterial infusion (HAI) combined or not with systemic chemotherapy for the treatment of unresectable colorectal liver metastases
Authors: P. Pilati, S. Mocellin, M. Lise, D. Nitti
Journal: Journal of Clinical Oncology (2007)

14565 Background: Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, there is substantial lack of evidence for benefit in terms of overall survival (OS). To test the hypothesis that systemic chemotherapy affects OS of patients with unresectable colorectal liver metastases treated with HAI. Furthermore, we investigated patient- and tumor-related predictive factors that might identify patients who most benefit from HAI regimen. Methods: In this retrospective study, 153 consecutive patients treated at our institution were considered. In group-A (n=72), patients were treated with HAI alone (floxuridine (FUDR) 0.2 mg/Kg + leucovorin (LV) 4 mg/m 2 + desamethasone 20 mg 14 days/month) between 1994 and 1999. In group-B (n=81), patients were treated with the same HAI regimen combined with systemic chemotherapy (5-fluorouracil (5FU) 450 mg/m 2 + LV 20 mg/m 2 ) between 1999 and 2003. Results: No difference in OS was observed between group-A and group-B (median OS: 18.0 and 19.1 months, respectively). Considering all patients (group A + group B), low tumor load was associated with a better tumor response rate, but none of the traditional clinico-pathological prognostic factors correlated with OS. Median OS was better in patients with less than 50% of liver parenchyma involvement (21.3 vs 13.2 months; P&lt;0.0001) as well as in responders (complete or partial response) versus non-responders (24.4 vs 13.4 months; P&lt;0.0001). The combination of low tumor load with good tumor response to HAI was the only variable retained at multivariate analysis, and identified a subgroup of patients with a very favorable clinical outcome (median survival: 34.2 months; hazard ratio: 0.347, CI: 0.249–0.564, P&lt; 0.0001). Conclusions: Combination with 5FU+LV systemic chemotherapy did not lead to an OS benefit over FUDR-based HAI alone. The identification of tumor response predictors is urgently needed, as it would lead to the tailored treatment of patients with low load but unresectable metastatic liver disease who most benefit from HAI therapy. No significant financial relationships to disclose.
Comparison of 1D, 2D, 3D and volumetric parameters in measuring tumor response in high-grade gliomas in adults
Authors: G. Shah, S. Kesari, R. Xu, J. Henson, T. Batchelor, F. Hochberg, A. Oneill, B. Levy, J. Bradshaw, P. Y. Wen
Journal: Journal of Clinical Oncology (2004)

1523 Background: : The RECIST criteria (1D measurement) is widely used to measure response in solid tumors but there are few studies validating this criteria in brain tumors. In a small study in childhood brain tumors, Warren et al. (JNCI 2001;92:205) found a high concordance between 1D, 2D and 3D measurements in detecting partial responses but not disease progression. More recently, Galanis et al (ASCO Abst 423, 2003) found that tumor responses assessed by RECIST and 2D measurements were equally associated with survival improvement. In this study we compared the 1D, 2D, 3D and computer assessed tumor volume (CV) measurements in adult brain tumors. Methods: : Tumor size on MRI scans in 80 patients with high-grade gliomas treated on clinical protocols were measured using 1D, 2D, 3D and CV. A total of 278 T1 post-gadolinium MRI scans (80 baseline and 198 follow up scans) were evaluated. Volumetric analysis was performed using VITREA. Results: Pearson correlation coefficients (ρ) with 95% confidence intervals (CI) are presented in the table for each measurement modality. All ρ values are greater than 0.70 with 95% CI no wider than 14%. Correlation was best between the 1D vs 2D and 2D vs 3D group. The poorest correlations were between the 1D and 3D and 1D and volumetric criteria. Median progression-free survival (MPFS) and 6-month progression free survival (6m-PFS) were 5.9 months (95% CI=5.0–7.6) and 45% (SD 6%) for 1 D, 6.0 m (5.1–7.6) and 47% (6%) for 2D, 6.0 m (5.1–7.7) and 47% (6%) for 3D, 6.2 m (5.1–8.2) and 49% (6%) for volumetric analysis. Conclusions: These results suggest that there is good concordance between the RECIST criteria and 2D measurements in determining response, MPFS and 6m-PFS in adult brain tumor patients. The correlations between 1D or 2D criteria and volumetric measurements are not as strong, but still high. No significant financial relationships to disclose.