tbuckley/cabot-search huggingface dataset:
Sister Chromatid Exchanges and Growth Inhibition Induced by the Flame Retardant Tris(2,3-dibromopropyl) Phosphate in Chinese Hamster Cells: Brief Communication 2
Authors: M. Furukawa, S. R. Sirianni, J. C. Tan, C. C. Huang
Journal: JNCI Journal of the National Cancer Institute (1978)

The effects of the flame retardant tris(2,3-dibromopropyl) phosphate (Tris-BP) on growth, sister chromatid exchanges (SCE), and chromosome aberrations of Chinese hamster V79 cells cultured either in vitro or in diffusion chambers (DC) implanted into mice were studied. Tris-BP caused a dose- and time-dependent reduction of cell growth as measured by colonyforming activities. A significant dose-dependent increase in SCE was observed in V79 cells either in the cultures treated with Tris-BP or In DC in mice given injections of the chemical. In contrast, Tris-BP in V79 cells in culture, in V79 cells in DC in mice, in two human lymphoid cell lines, or in mouse bone marrow cells in vivo did not significantly increase chromosome aberrations.
The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children
Authors: Mohammadreza Modaresi, Perinaz Poursafa, Roya Kelishadi, S.H. Javanmard
Journal: European Respiratory Journal (2011)

Background:  This study aimed to assess the relationship of air pollution and plasma surrogate markers of endothelial dysfunction in the pediatric age group.   Methods:  This cross-sectional study was conducted in 2009-2010 among 125 participants aged 10-18 years. They were randomly selected from different areas of Isfahan city, the second large and air-polluted city in Iran. The association of air pollutants9 levels with serum thrombomodulin (TM) and tissue factor (TF) was determined after adjustment for age, gender, anthropometric measures, dietary and physical activity habits.   Results:  Data of 118 participants was complete and was analyzed. The mean age was 12.79 (2.35) years. The mean pollution standards index (PSI) value was at moderate level, the mean particular matter measuring up to 10 mum (PM10) was more than twice the normal level. Multiple linear regression analysis showed that TF had significant relationship with all air pollutants except than carbon monoxide, and TM had significant inverse relationship with ozone. The odds ratio of elevated TF was significantly higher in the upper vs. the lowest quartiles of PM10, ozone and PSI. The corresponding figures were in opposite direction for TM.   Conclusions:  The relationship of air pollutants with endothelial dysfunction and pro-coagulant state can be an important factor in the development of atherosclerosis from early life. This finding should be confirmed in future longitudinal studies. Concerns about the harmful effects of air pollution on children9s health should be considered a top priority for public health policy; it should be underscored in primordial and primary prevention of chronic diseases.
Tonsillectomy and Hodgkin's Disease: Results From Companion Population-Based Studies2
Authors: Nancy Mueller, G. Marie Swanson, Chung-cheng Hsieh, Philip Cole
Journal: JNCI Journal of the National Cancer Institute (1987)

The question of whether persons with a history of tonsillectomy are at increased risk of Hodgkin's disease (HD) in adulthood was evaluated in companion population-based case-control studies conducted in the eastern Massachusetts and the Detroit metropolitan areas. These studies compared the history of tonsillectomy among incident cases with that of all their siblings by matched analysis controlling for confounding by childhood social class, family size, and birth order. Among young adults (15-39 yr) there is substantial evidence that tonsillectomy is not a risk factor and the relative risk (RR) is 1.0 (95% confidence interval, 0.72-1.4). Among middle-aged persons (40-54 yr) the RR is not significantly elevated, 1.5 (0.67-3.3), and the direction of the association differs between the sexes, consistent with the hypothesis of no association. Among older persons, the RR is significantly elevated, 3.0 (1.3-6.9), but the data are sparse. On the basis of these data, it appears unlikely that prior tonsillectomy is a causal factor in the development of HD in young and middle-aged adulthood. Whether it is a risk factor for the malignancy occurring late in life is unclear.
Efficacy of Anti-Her2 Retherapy with Trastuzumab at First Relapse and/or First Occurrence of Metastases of Her2-Positive Breast Cancer in Clinical Routine – 4Th Interim Analysis of the Non-Interventional Study (Nis) Ml21589
Authors: L. Hanker, T. Hitschold, A. Grafe, F. Förster, J. Schröder, J. Janssen, D. Reichert, T. Wohlfarth, J. Greinemann, T. Hesse
Journal: Annals of Oncology (2014)
Evaluation of the melanocortin-1-receptor gene in melanoma predisposition, progression, and recurrence
Authors: S. Sidash, H. Ostrer, J. D. Goldberg, I. Belitskaya-Levy, I. V. Lobach, D. Polsky, R. L. Shapiro, R. S. Berman, I. Osman, P. Manga
Journal: Journal of Clinical Oncology (2009)

9018 Background: The melanocortin-1-receptor (MC1R) gene is highly polymorphic in humans. Multiple studies have shown the association between MC1R allelic variants and increased risk of melanoma. Over seventy MC1R single nucleotide polymorphisms (SNPs) have been identified making MC1R a likely target for the development of genetic markers for melanoma predisposition and progression. Alleles described as R and r result in a protein with reduced function compared to wild type, with r alleles having the greatest effect. We sought to investigate the impact of MC1R genotype on risk of developing melanoma and will test for association with disease progression and recurrence in a cohort of melanoma patients enrolled in a prospective study. Methods: Our cohort includes 291 newly diagnosed melanoma patients seen at the New York University Langone Medical Center. The control cohort included 449 subjects. DNA was isolated from leukocytes and analyzed for MC1R SNP status by PCR and direct sequencing. Associations were tested for R-variant R151C and r-variants V60L and V92M. Fisher's Exact test was used to detect significant differences in allele frequency. Odds ratios and confidence intervals were computed for each SNP. Results: Allele frequencies were significantly different in cases and controls for each of the variants (p&lt;0.01). The greatest effect was seen with V60L (Odds Ratio=6.281 95% Confidence Interval 1.77- 22.20). Conclusions: Variants that result in reduced MC1R function increase an individual's risk of developing melanoma. We will continue to test associations with additional variants and determine if these alleles also contribute to risk of disease progression and recurrence. In addition, these variants will be tested for utility as biomarkers for risk assessment of melanoma in a clinical setting. No significant financial relationships to disclose.
Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer.
Authors: J R Jett, A W Maksymiuk, J Q Su, J A Mailliard, J E Krook, L K Tschetter, C G Kardinal, D I Twito, R Levitt, J B Gerstner
Journal: Journal of Clinical Oncology (1994)

PURPOSE We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR). PATIENTS AND METHODS One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months. RESULTS Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years. CONCLUSION Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.
LSC 2011 Abstract: An expression survey of toll-like receptors (TLRs) and nod-like receptors (NLRs) in allergic asthma
Authors: Seil Sagar, Kim A.T. Verheijden, Aletta D. Kraneveld, Niki Georgiou, Gert Folkerts, Johan Garssen
Journal: European Respiratory Journal (2011)

Allergic disorders, such as asthma, are symptomatic reactions of the immune system to common and innocuous environmental antigens. These inflammatory disorders are caused by aberrant immune regulation in which various signalling receptors are involved. Pathogen recognition receptors like the TLRs and NLRs families of receptors are one of the key components of the innate immune system. The function of these receptors has been linked with susceptibility towards the development of allergic diseases, including asthma, making the TLRs and NLRs good targets for novel effective therapies of allergic diseases. In this study the mRNA expression levels of different TLRs and NLRs in the lung tissue in mild and severe mouse models of allergic asthma were measured by q-PCR. In addition, broncho-alveolar lavage fluid (BALF) was collected and cell numbers analysed. In the mild and severe asthma models different TLR and NLR mRNA expression profiles are observed. In the severe asthma model, a higher cell influx in BALF is seen. Moreover, a significant correlation is found between the mRNA expression of TLR3, TLR6 and TLR9 and the total cell number in the BALF.
Relation between Insulin-like growth factor-1 receptor (IGF-1R) expression and the efficacy of trastuzumab (T) monotherapy for hormone-resistant HER2-postitive metastatic breast cancer (MBC)
Authors: C. Shimizu, T. Hasegawa, M. Ando, Y. Fujiwara, Y. Tani
Journal: Journal of Clinical Oncology (2004)

9578 Background: T is an active drug for HER2-positive MBC with excellent toxicity profile, but its anti-tumor effect as monotherapy is limited and the mechanism of T resistance is not elucidated. Lu Y et al. recently demonstrated in human breast cancer cell-lines that increased level of IGF-1R signaling adversely interferes with T's action on cell growth (JNCI, 2001). We assessed the predictive value of IGF-1R protein expression for T therapy in tumor samples using immunohistochemistry(IHC). Methods: Between June 2001 and May 2003, 39 patients without visceral crisis were treated with T monotherapy as the first line therapy for hormone-resistant MBC. All tumors were HER2 positive either by Herceptest(3+) or FISH. Among them, 26 formalin-fixed paraffin embedded tissue of primary or metastatic lesions were available. Mouse monoclonal antibody (clone 24–31) specific for alpha subunit was used for IGF-1R IHC. ER, PgR, IGF-BP3 was also evaluated by IHC. IGF-1R and IGFBP3 expression levels were measured from its staining on the membrane and cytoplasm, respectively, as mode-intensity (MI) by automated imaging analyzer(Ariol SL-50). T monotherapy was continued until clinical progression. Results: Median duration of T monotherapy was 78 days (range 20–375). The range of MI for IGF-1R and IGF-BP3 was 0–166.7 (mean 86.0, SD 40.8) and 0–86.4 (mean 57.3, SD 28.3), respectively. Neither IGF-1R MI nor IGF-BP3 MI correlated with duration of T monotherapy (p=.692 and .791, respectively). High IGF-1R MI (>50.0) was observed in 5 out of 6 patients who received T monotherapy more than 12 weeks without progression (1 CR, 5 MR), and 4 of the 5 patients showed high IGFBP3 MI(>50.0). Conclusions: In contrast to previously reported in vitro experiment, IGF-1R protein expression did not correlate with resistance to T monotherapy. Further studies are necessary to clarify the role of IGF-1R axis in mechanism of action of T. No significant financial relationships to disclose.
A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of farletuzumab (MORAb-003) in combination with weekly paclitaxel in subjects with platinum-resistant or refractory relapsed ovarian cancer.
Authors: L. Elit, J. A. Konner, D. K. Armstrong, M. Buck, A. Dean, N. J. Finkler, A. Hulstine, C. Schweizer, M. Phillips, S. Weil
Journal: Journal of Clinical Oncology (2010)

TPS255 Background: Farletuzumab (MORAb-003) is a humanized monoclonal antibody that binds to the folate receptor alpha (FRA) which is overexpressed in most epithelial ovarian cancers (EOC), but largely absent on normal tissue. The expression of FRA is known to relate to the malignant potential of the cancer. Farletuzumab has been shown to inhibit phosphorylation of proteins by the Lyn kinase (a member of the src family of kinases). It inhibits tumor growth in preclinical xenograft models of ovarian cancer, in addition to being active in antibody-dependent cellular cytotoxicity (ADCC) assays (Ebel W et al. Cancer Immun 2007; 7:6). It showed signs of efficacy as a single agent in a phase I study in subjects with advanced platinum refractory/resistant EOC (Bell-McGuinn KM et al. J Clin Oncol 2008;26 (15S):5517). In this phase I study, as well as in a subsequent phase II study (Armstrong DK. et al. 2009 ECCO and ESMO Congress, Abstract 08000), farletuzumab demonstrated a favorable safety profile. Weekly low dose paclitaxel (80mg/m2) shows promise as a single agent in platinum refractory/resistant EOC with an overall response rate of about 21%, and a median duration of remission of 3 months (Markman M. et al. Gynecologic Oncology 2006;101:436-440). In a xenograft model, synergy between taxane and farletuzumab has been demonstrated ( Spannuth WA et al. Gynecologic Oncology 2008: 108(3S):S135). In this study we are comparing the efficacy of farletuzumab when combined with paclitaxel in platinum refractory/resistant EOC. Methods: 126 subjects with platinum-resistant/refractory nonmucinous EOC receive paclitaxel and are randomized 2:1 to receive farletuzumab:saline placebo IV. Farletuzumab/placebo is administered weekly. Paclitaxel is administered weekly for the first 12 weeks, then in 4 week cycles with week 4 being a rest week (Markman M. et al. Gynecologic Oncology 2006;101:436-440). The primary endpoint is progression-free survival. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Morphotek Morphotek Morphotek Morphotek
P04 Admission serum lactate is a strong predictor of outcome in cirrhotics admitted to intensive care unit, and when added to the liver-specific scores of model for end-stage liver disease or UK model for end-stage liver disease, improves their respective predictive value
Authors: A Burroughs, M Garcovich, V Vemala, B Agarwal, A Davenport, S Shaw, J O'Beirne
Journal: Gut (2010)

Introduction  Accurate prognostic indicators of patient survival in an intensive care unit (ICU) help guide clinical decision-making. Factors known to portend poor prognosis in acutely ill cirrhotics in ICU include the need for mechanical ventilation, development of shock, renal failure and sequential increase in the number of failing organs. While serum lactate is now an established marker of survival and/or the need for transplantation in fulminant liver failure, its impact on critically ill cirrhotics is less well known.  Method  We retrospectively studied 133 consecutive acutely ill cirrhotics admitted to the ICU between 2005 and 2008 at the Royal Free Hospital, a tertiary referral centre in liver diseases and transplantation. Data were collected on demographic variables, aetiology of liver disease, liver-specific prognostic scores (Child–Turcotte–Pugh (CTP), model for end-stage liver disease (MELD), UK model for end-stage liver disease (UKELD)), and acute illness scores (acute physiological score and chronic health point (APACHE II), sequential organ failure assessment score (SOFA)). In addition, serum lactate levels at 0, 24 and 48 h were also recorded. Multivariable logistic regression analysis was performed, and the discrimination ability of each of the above-mentioned scoring models in predicting ICU and hospital survival of these patients was evaluated using the area under the receiver operating characteristic (ROC) curve.  Results  The ICU and hospital non-survivors—43/133 (32.3%) and 57/133 (43.4%) respectively—had similar demographic features as the survivors, but had significantly higher mean admission MELD, UKELD, SOFA and APACHE II scores, as well serum lactate levels on admission. Serum lactate at admission and particularly at 24 h had a better discriminative accuracy for mortality (AUC=0.737 and 0.764) compared with liver-specific prognostic scores, MELD (AUC=0.732 and 0.720), MELD-Na (AUC=0.338 and 0.554) and UKELD (AUC=0.698 and 0.695). Acute illness scores exhibited a rather poorer predictive power, both APACHE II (AUC=0.632 and 0.571) and SOFA (AUC=0.688 and 0.716). Adding lactate to MELD and UKELD scores further improved their outcome prediction potential (AUC MELD-lactate=0.737 and UKELD-lactate=0.717).  Conclusion  Serum lactate is a powerful independent tool in predicting survival of acutely ill cirrhotics on ICU. Persistent hyperlactataemia after aggressive resuscitation for 24 h may reflect native liver9s inability to metabolise it. In that case, should lactate not be incorporated in the liver function scoring models such as CTP, MELD or UKELD?
BCIRG 001 molecular analysis: Identification of prognostic factors in patients (pts) receiving adjuvant therapy for node- positive (N+) breast cancer (BC)
Authors: C. M. Dumontet, J. C. Reed, M. Krajewska, I. Treilleux, J. R. Mackey, M. Martin, C. Vogel, M. Rupin, E. Brunel, J. Hugh
Journal: Journal of Clinical Oncology (2007)

525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubicin/cyclophosphamide (TAC) over fluorouracil/doxorubicin/cyclophosphamide (FAC) given as adjuvant therapy for N+ operable BC in terms of disease-free survival (DFS) and overall survival (OS) (Martin et al, N Eng J Med, 2005). This ancillary study was aimed to identify tumor-associated factors related to DFS and OS. Methods: Formalin-fixed primary tumors from pts in BCIRG 001 were analysed by immunohistochemistry. Protocol- specified assessment of histological grade (GR), tumor size (TS), estrogen (ER) and progesterone receptors (PR), lymph node status (LN), HER2, MUC1, Mib, p53, Bcl-2, Bax, Bcl-X, Bag-1, tubulin β isotypes II, III and IV, tau protein and detyrosinated a tubulin was performed. Parameters were scored as the percentage of positive cells and analysed as lower or greater than median values. The samples were randomly split into training (2/3) and validation (1/3) sets. Associations between selected parameters and DFS or OS were tested through univariate analyses using the Kaplan Meier method (log-rank test) on the training set. A backward stepwise Cox regression analysis was performed to identify the final model of prognostic factors on the training set. Multivariate analyses were applied to the validation set. Results: 1,350 samples were split into a training (n=906) and a validation (n=444) set. In univariate GR, TS, LN, ER and PR, Mib, tau protein and HER2 were correlated with DFS in both sets. In multivariate ER, PR, TS, LN, Mib (all p&lt;0.01) and tau (p=0.043) were significantly associated with DFS in the training set. In univariate GR, TS, LN, ER and PR, Mib, MUC1, Bcl-2, tubulin III and IV and tau were correlated with OS in both sets, with a trend for p53. In multivariate ER, TS, LN, Mib, p53 (all p&lt;0.01) and PR (p=0.028) were independently correlated with OS in the training set. Conclusions: These data suggest that tau and p53 are independent markers of DFS and OS, respectively, while Mib is correlated with both DFS and OS in pts receiving these forms of adjuvant chemotherapy for N+ BC. Complementary analyses will be presented. No significant financial relationships to disclose.
Baseline characteristics, prior bisphosphonate (BPH) therapy (Rx), and clinical parameters of patients in LOTUZ, a prospective pharmacoepidemiological study of long-term zoledronic acid (ZOL) treatment (≥2 years) in patients (pts) with solid and hematologic malignancies
Authors: H. Wildiers, L. Duck, M. Delforge, C. Doyen, A. Lefever, C. Wouters, K. MacDonald, I. Abraham
Journal: Journal of Clinical Oncology (2008)

20597 Background: There is a trend towards long-term Rx with ZOL. The LOTUZ study is among the first to examine ZOL Rx treatment patterns, effectiveness, and safety beyond 2 years. Reported are baseline characteristics, prior BPH Rx, and clinical parameters of enrolled pts. Methods: Prospective (18 months [mths]), multicenter (50 centers), pharmacoepidemiological study on pts with ZOL Rx ≥2yrs (3–4wk schedule). Endpoints: skeletal-related events (SREs), skeletal morbidity, pain, and safety (general, renal, osteonecrosis of jaw [ONJ]) as associated with variability in treatment patterns and patient risk profiles. 191 pts recruited for evaluable sample of 189 pts. Results: Pts’ age ranged from 37.7–88.0yrs (M±SD=65.2±11.0). Most were female (66.7%). 91.5% had performance status ≤1. 66.7% had metastatic bone disease due to solid tumor (breast 49.7%, prostate 12.7%, other 3.7%; mean duration [MD] 4.1±2.4yrs) and 33.3% multiple myeloma (MD=4.9±2.9 yrs). Prior cancer therapy: pharmacotherapy (98.9%, incl. 60.3% hormonal, 77.8% chemo, 64.0% corticosteroids, and 12.2% other agents), skeletal (49.2%) and nonskeletal (37.0%) radiotherapy and skeletal surgery (9.5% of pts). 30.2% had non-ZOL BPH Rx prior to ZOL Rx (MD=20.2±15.7 months). Pre-enrollment ZOL Rx ranged from 23–80.5 mths (M±SD=38.9±9.9) with 62.8% treated for ≥3yrs. 58.2% had prior SREs: 40.7% radiotherapy to bone, 20.1% bone pain requiring BPH, 12.2% spontaneous fracture, 10.1% bone surgery, 2.1% spinal compression, 1.1% hypercalcemia. Mean time since last SRE was 32.4±20.5 mths (range 2.3–92.4). 20% received calcium and 14% Vit D. At inclusion 1.1% had a dental extraction, 4.2% gingivitis, 0.5% dental/sinus infection, 0.5% jaw trauma/fracture. Serum creatinine was 0.4–2.1mg/dL [M±SD=0.9±0.3]. 6.3% had stage 3 renal disease. Conclusions: LOTUZ is among the first studies on safety and effectiveness of long-term (≥2yrs) ZOL Rx. Baseline data provide an initial profile of patients considered for long-term ZOL Rx in Belgium. On behalf of Belgian Society of Medical Oncology (H.W., L.D.) and Belgian Hematology Society (M.D., C.D.). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Cameroon's multidrug-resistant tuberculosis treatment programme jeopardised by cross-border migration
Authors: Alberto Matteelli, Knut Lönnroth, Davide Mosca, Haileyesus Getahun, Rosella Centis, Lia D'Ambrosio, Ernesto Jaramillo, Giovanni Battista Migliori, Mario C. Raviglione
Journal: European Respiratory Journal (2016)

We read with interest the correspondence from J. Noeske and colleagues on the potential effect of cross-border migration on the multidrug-resistant tuberculosis (MDR-TB) treatment programme in Cameroon, elicited by our article on the framework for TB elimination in low TB incidence countries [1]. The manuscript highlights some of the consequences of cross-border migration for caring for people with TB and ending this epidemic, as well as relevant issues on clinical and public health management of MDR-TB in Cameroon. Cross-border migration: migrant and native populations' health cannot be ignored by national TB programmes <http://ow.ly/U7TO4>