tbuckley/cabot-search huggingface dataset:
Different chromosomal alterations correlate with gene expression in African American (AA) versus Caucasian American (CA) prostate cancer (PC) patients
Authors: J. Jean-Gilles, J. Satagopan, Q. Zhou, A. Dash, J. Yu, P. Lee, H. I. Scher, W. Gerald, I. Osman
Journal: Journal of Clinical Oncology (2007)

5000 Background: We used a genome wide approach to identify chromosomal and gene expression alterations that might explain the aggressive clinical behavior of PC in AA compared with CA patients. Methods: We frequency matched 20 AA with 20 CA patients for potential confounding factors (PSA, age, Gleason grade, pathologic stage). We utilized array-CGH (Spectral Genomics), to identify noteworthy genomic regions with significantly different chromosomal alterations between the 2 groups. RNA samples were available for 19 AA and 14 CA patients. Gene expressions were examined using Affymetrix HG-U133 Plus 2.0 arrays. Correlations were examined between the noteworthy altered chromosomal regions and gene expression. Results: Regions of chromosomal gain or loss in each sample were determined using the circular binary segmentation approach coupled with an outlier detection method to identify singleton markers exhibiting alterations. We identified 28 chromosomal regions that were significantly different between the 2 cohorts (Fisher’s exact test). 11 regions (3q28- 29, 3q25–26, 4p12–14, 4p13, 9q21, 10q11, 11q14, 12p13, 14q12, 16p11, 20p11–20q11) were more commonly altered in AA patients compared to CA patients (P&lt;0.005). The altered chromosomal regions were associated with corresponding gene expression changes. Gene ontology and pathway analyses showed a relatively short list of affected pathways: insulin, STAT, TGF-beta signalings, proteosome degradation, integrin- mediated cell adhesion, adipose and calcium metabolisms. Hierarchical clustering of the 33 patients (19 AA and 14 CA) based on the shortlist of gene expressions showed two clusters, one consisting of CA and the other with AA patients, with only 3 AA patients showing similar gene expression to CA group and vice versa. Conclusions: Data demonstrate the presence of biologic differences between the AA and CA cohort of patients studied and suggest that the disproportionately unfavorable outcome of PC in AA patients cannot solely be explained by advanced tumor at presentation. Validation in an independent larger sample size is a prerequisite before further conclusions can be made. No significant financial relationships to disclose.
Polychemotherapy (CT) in pre- and post-menopausal women with early breast cancer prescribed 5 years tamoxifen (T) –results from the UK NCRI Adjuvant Breast Cancer (ABC) international trial in 1991 patients
Authors: P. J. Barrett-Lee, J. M. Bliss, A. M. Brunt, K. Dehshiri, A. N. Harnett, L. Johnson, D. Lawrence, A. Robinson, K. Weerasekera
Journal: Journal of Clinical Oncology (2004)

656 Background: EBCTCG 2000 systematic overview confirmed overall survival advantage of CT in early breast cancer (BC), but doubts remain over these benefits in presence of concomitant prolonged tamoxifen (T) and ovarian ablation (OA) in premenopausal women. Methods: The ABC trial is a pragmatic, randomised phase III trial. One aspect of ABC compared CT (any type but CMF recommended) vs. none in patients with early (1–3a) BC. All patients prescribed 20mg T for 5 years. Patients could receive OA or not as elective treatment. Main endpoints: relapse-free survival (RFS) and overall survival (OS). Results: During 1993 to 2000, 1991 (987 CT, 1004 no CT) patients were randomised from 106 UK and 16 non-UK centres. Pre-treatment patient characteristics were well-balanced. In total 62% patients were age >50 years, 56% node positive, and 64% oestrogen receptor (ER) positive. 92% patients received CT as allocated. Type of CT was CMF (87%), anthracycline containing (11%). 244 patients received OA. Results based on median follow-up of 5.0 years, 601 relapses and 485 deaths. CT suggested an improvement in RFS (HR 0.86 [95%CI 0.73–1.01] p=0.061) and OS (HR 0.87 [95%CI 0.73–1.04] p=0.12) but unadjusted results did not reach conventional levels of statistical significance. Adjusting for nodal status, ER, age, OA slightly increases magnitude of benefit of CT (RFS: HR 0.83 (0.71–0.97) p=0.024, OS: HR0.84 (0.70–1.00) p=0.051). Results (RFS) were independent of ER status. Impact appeared greater for women aged <50 (<50 HR 0.76 [0.57–1.01], ≥50 HR 0.89 [0.73–1.09]), for those (pre-menopausal) not receiving OA (without OA HR 0.71 [0.47–1.08], with OA HR 0.94 [0.56–1.56]) and for those from centres with good CT compliance (good CT HR 0.83 [0.68–1.01], poor CT HR 0.95 [0.71–1.25]). Conclusion: This is the first report of CT in women with early BC receiving concomitant and 5-year duration T, showing that benefits of CT are retained in this context. No significant financial relationships to disclose.
Abstract P215: Common Beta-cell-associated Genetic Variants and Hypertension or Anti-hypertensive Drugs do not Interact in Their Positive Associations With Risk for Rising Fasting Glucose or Incident Type 2 Diabetes in Framingham
Authors: Jose M de Miguel-Yanes, Bianca Porneala, Michael J Pencina, Caroline S Fox, Jose C Florez, David S Siscovick, Josèe Dupuis, James B Meigs
Journal: Circulation (2012)

Background: Hypertension (HTN) and some anti-HTN drugs raise fasting glucose (FG) levels and type 2 diabetes (T2D) risk. We hypothesized that common single nucleotide polymorphisms (SNPs) associated with FG or T2D that influence beta-cell function will interact with hypertension (HTN) or anti-HTN drugs in their positive associations with change over time in FG (ΔFG) or incident T2D. Methods: We studied 3,471 Framingham Offspring Study participants comprising 18,786 person-exams (mean age 49 yr; 54% women), in pooled (7 ∼4-yr periods) age-, sex-adjusted logistic regression models predicting T2D incidence, or age-, sex-, baseline FG-adjusted mixed linear models testing ΔFG (FG end minus beginning of period). T2D cases were excluded at baseline of each period, and people who started T2D treatment within a given period were removed for ΔFG analyses. We defined three HTN exposures: 1) HTN (SBP≥140/DBP≥90 mmHg) vs. no-HTN; 2) treated vs. untreated HTN; 3) five mutually-exclusive anti-HTN drug categories (beta-blockers, thiazides, renin-angiotensin system agents, combination, other) vs. untreated HTN, and two genetic exposures reflecting total beta-cell genetic risk burden: 16 FG-SNP and 33 T2D-SNP (only 8 overlap) additive genetic risk scores. We tested ∼4-year mean ΔFG and odds of T2D by HTN category and per-risk allele change in SNP scores, seeking first-order HTNxSNP significant interaction (P&lt;0.05). Results: Versus no HTN, HTN (n=5,372 p-e) was associated with higher ∼4-year ΔFG (0.14 vs. 0.03 mmol/l; P&lt;0.0001) and ∼3-fold increased odds of T2D (OR 3.3; P&lt;0.0001). Versus untreated HTN, treated HTN (n=2,832 p-e) conferred higher ΔFG (0.18 vs. 0.12 mmol/l; P&lt;0.0001) and 1.5-fold increased odds of T2D (P=0.0006). Versus untreated HTN, beta-blockers (n=676 p-e; OR=1.58), combined (n=499 p-e; OR=1.57) and other (n=569 p-e; OR=1.94) were associated with increased odds of T2D (all P&lt;0.03). Per-SNP score risk allele, ΔFG increased by 0.03 mmol/l (P=2.2x10 −16 ) and odds of T2D increased 17% (P=3.1x10 −08 ). In joint models with interaction terms, all HTN-treatment category-by-SNP score interaction terms were non-significant. In joint models without interaction, HTN (P&lt;0.0001) and HTN treatment (P&lt;0.02), but no specific drugs (all but one P&gt;0.02), and per FG-SNP or T2D-SNP risk allele (highest P value=0.0005), all independently predicted ΔFG or incident T2D. Conclusion: HTN, HTN treatment and common FG- and T2D-SNP genetic scores were independently associated with ΔFG and T2D incidence, but did not modify each other's association with ΔFG or T2D risk. Next, larger samples and individual SNP-by-specific drug category interaction tests might disclose some biological basis for T2D risk associated with anti-HTN therapy.
Malignant Transformation of Rat Embryo Fibroblasts by Carcinogenic Fluorenylhydroxamic Acids In Vitro2
Authors: L. I. Sekely, D. Malejka-Giganti, H. R. Gutmann, R. E. Rydell
Journal: JNCI Journal of the National Cancer Institute (1973)

The capacity of several fluorenylhydroxamic acids and their acetate esters to transform Wistar rat-embryo fibroblasts grown in mass culture was investigated. N-Hydroxy-2-fluorenylacetamide, N-hydroxy-3-fluorenylacetamide, N-acetoxy-2-fluorenylacetamide, N-acetoxy-3-fluorenylacetamide, and N-hydroxy-2-fluorenylbenzamide induced morphologic alterations commonly associated with malignant transformation. Untreated controls did not change morphologically. Inoculation of carcinogen-treated cells into Wistar or Sprague-Dawley rats gave a high incidence of transplantable fibrosarcomas. Untreated cells yielded no tumors. Addition of cysteamine to rat embryo fibroblasts beFore exposure to N-hydroxy-2-fluorenylacetamide and N-hydroxy-2-fluorenylbenzamide reduced the latent period and increased the tumor yield. Preliminary studies indicated that rat embryo fibroblasts, unlike rat livers, do not activate N-hydroxy-2-fluorenylacetamide by sulfonation. This suggests that the mechanism underlying the transformation of rat embryo fibroblasts is different from that considered to account for the malignant transformation of the rat hepatic cell.
Nasal non-invasive positive pressure ventilation for moderate exacerbation of chronic obstructive pulmonary disease (COPD) treated in a Tunisian medical ward
Authors: Ibtihel Khouaja, Habib Ghedira
Journal: European Respiratory Journal (2012)

Nasal Non-Invasive Positive Pressure Ventilation (NNPPV) is a soft method with a low burden which can be used in medical ward and may improve the outcome of COPD exacerbation.  Aim: The aim of this study is to evaluate the effectiveness of the addition of NNPPV to usual medical care in improving the outcome of patients treated in a medical ward for an exacerbation of COPD with moderate hypercapnia.  Methods: Among 25 patients who were hospitalized for an exacerbation of COPD with moderate hypercpnia, 10 were randomly selected to receive NNPPV (NNPPV group) and then compared to the 15 patients who received only an optimal medical treatment without ventilation support (control group).  Results: The age of patients who received NNPPV did not differ from that of control group (63 ± 10 yrs-old vs 66 ± 9 yrs-old; p = 0,31) and neither did the blood gas on admission (PaO2: 46 ± 9 vs 49 ± 12 mmHg; p=0,56; PaCO2 : 58 ± 12 mmHg vs 57 ± 9 mmHg; p=0,80; pH : 7,39 ± 0.1vs 7,38 ± 0.06, p = 0, 8). None of the patients treated with NNPPV died or was transferred to ICU while 2 died and 3 were transferred to ICU among patients of control group. Also, time to improve for blood gas parameters was shorter and on day one we recorded a ΔPaO2 = 33.6 ± 14 mmHg in NNPPV group vs 17.28 ± 19 mmHg in control group (p=0,02) and a ΔPaCO2 =-4 ± 13 mmHg in NNPPV group vs 16 ± 7.5 mmHg in control group (p=0,04).  Results: NNPPV in COPD patients treated for an exacerbation with moderate hypercapnia shortens time to improve of blood gas and is likely to reduce mortality and the need of more invasive ventilation methods.
Salvage chemotherapy with high-dose carboplatin and etoposide (HDCE) with peripheral blood stem cell transplant (PBSCT) in patients with relapsed seminoma
Authors: S. M. Herbert, R. Abonour, L. H. Einhorn M.D.
Journal: Journal of Clinical Oncology (2007)

5054 Background: Patients with relapsed seminoma are treated with salvage chemotherapy. Current therapeutic options include cisplatin plus ifosfamide based regimens or high dose chemotherapy with PBSCT. At Indiana University HDCE was usually reserved for third line therapy for relapsed seminoma, unless there were visceral metastases or relapse within 3 months of initial chemotherapy. Methods: Retrospective review of 35 consecutive patients with pure seminoma (median 38 yrs; range 23–56 yrs) that received HDCE with PBSCT from 2/96–12/04. Cytoreductive chemotherapy with 0–2 courses of vinblastine, ifosfamide, and cisplatin (VeIP) preceeded HDCE. Carboplatin dosage was 700mg/m 2 for 3 days plus etoposide 750mg/m 2 for 3 days. A second course of therapy was given after hematopoietic recovery. Results: Treatment related mortality was seen only in patients that received two or more prior regimens (median age 45 yrs, range 27–56 yrs) and occurred in 4/35 (11%) patients. One man died of AML at 62 months (see table below). 26/35 (74%) are continuously NED (cNED). 15/35 patients received 1 prior regimen and 14/15 (93%) are cNED. 20/35 patients received =2 prior regimens and 12/20 (60%) are NED. 14/35 patients had prior XRT. 10/14 (71%) are cNED. 6/14 patients had prior XRT and =2 prior regimens and 3/6 (50%) are NED. Conclusions: HDCE with PBSCT has a high cure rate even when used as 3 rd line or later therapy. Because of the 93% continuous NED rate when used as 2 nd line therapy and the increased treatment related mortality when used as 3 rd line therapy we now recommend HDCE as initial salvage therapy. [Table: see text] No significant financial relationships to disclose.
Fever and Neutropenia Clinical Practice Guidelines in Oncology
Authors: Alison G Freifeld, Lindsey Robert Baden, Arthur E Brown, Linda S Elting, Michael Gelfand, John N Greene, James I Ito, Earl King, Guido Marcucci, Jose G Montoya, Ashley Morris, Gary Noskin, Ken Rolston, Anne F Schott, Brahm Segal
Journal: Journal of the National Comprehensive Cancer Network (2004)

Substantial improvements have occurred in the management of infectious disease in patients with cancer. It is now unusual for patients with acute leukemia who receive their initial induction chemotherapy at a major center to die of infectious complications. Many patients will undergo further therapy that leads to prolonged periods of neutropenia without succumbing to a major infectious complication. However, managing infections in neutropenic patients remains a dynamic process, affected by the appearance of new pathogens, the emergence of antibiotic-resistant organisms, and the improved stratification of patients' infection risk. All of these factors have fostered new treatment approaches. These NCCN clinical guidelines address many of the day-to-day issues inherent in managing fever and neutropenia. For the most recent version of the guidelines, please visit NCCN.org
PTH-116 Evaluation of the d’amico clinical staging system and the albi grade for prognostication in cirrhosis and hepatocellular carcinoma
Authors: R Kia, I Buck, K Clark, A Halpen, C Farrell, D Palmer, TJS Cross
Journal: Gut (2015)

<h3>Introduction</h3> The ability to prognosticate in both cirrhosis and hepatocellular carcinoma (HCC) is vital for correct treatment decisions. For HCC, many staging systems incorporate tumour characteristics but inadequately consider underlying liver dysfunction. Therefore, models that accurately stratify the degree of liver dysfunction, may improve our understanding of its impact on survival in patients with HCC. We aimed to compare current and potential prognostication models of survival for patients with cirrhosis, and to determine their applicability in HCC patients. <h3>Method</h3> A single-centre retrospective comparative analysis of cohorts of consecutive patients diagnosed with cirrhosis alone was performed against HCC patients with background cirrhosis. The Child-Pugh score, MELD score, UKELD score, the D’Amico clinical stage of cirrhosis (D’Amico G, <i>et al</i>., J Hepatol, 2006) and the Albumin-Bilirubin (ALBI) grade – a composite model of liver function using serum bilirubin and albumin levels (Johnson PJ, <i>et al</i>., J Clin Oncol, 2015), were determined at diagnosis. The patient outcome at 1 year post diagnosis was also determined. The primary outcome was the models’ ability to predict death at 1 year. The impact of liver dysfunction on survival in patients with HCC was also evaluated. <h3>Results</h3> A total of 117 patients were included in this study (67% male, median age: 57 years). The aetiologies were ALD (52%), NASH (15%), HCV (11%), PBC (5%), HBV (2%), AIH (2%), mixed aetiology (9%) and others (5%). 75% of patients had cirrhosis alone while 25% had HCC. All the evaluated models accurately predicted death at 1 year (all with p &lt; 0.001). The risk of death was greater amongst patients with HCC (p = 0.04; OR 2.6, 95% CI: 1.1–6.3) compared to patients with cirrhosis alone, despite favourable levels of albumin (37 vs. 35 g/L, p = 0.003), bilirubin (25 vs. 87 μmol/L, p &lt; 0.0001) and prothrombin time (12 vs. 16 s, p &lt; 0.0001). D’Amico stage 3–4 also predicted a significantly increased risk of death for cirrhotic patients (p &lt; 0.0001; OR 5.7, CI: 2.4–14). <h3>Conclusion</h3> All the evaluated prognostication models performed well, though the study was limited by a small cohort of patients with HCC. Despite a better liver function, the survival of patients with HCC was inferior, suggesting that tumour biology has a greater impact overall compared to the degree of underlying liver dysfunction. However, future studies specifically looking at the impact of liver dysfunction on survival in non-surgical treatment of HCC should be considered. <h3>Disclosure of interest</h3> None Declared.
Israeli agents raid Hebron hospital and kill visiting relative of wanted man
Authors: O. Dyer
Journal: BMJ (2015)

Agents of Israel’s security service, disguised as the family of a woman in labour, raided a West Bank hospital last week (12 November) to arrest a wounded man accused of stabbing an Israeli settler. The man’s cousin was shot and killed during the raid.

Security video footage from the entrance corridor of the Al-Ahli hospital in Hebron showed four bearded and moustached men pushing a wheelchair carrying an apparently pregnant woman in a niqab. On reaching the reception desk the apparent woman stood up and produced a handgun, as did the others, and at least a dozen more armed men entered. They shouted commands to watching hospital …
Atypical patterns of response in patients (pts) with metastatic melanoma treated with pembrolizumab (MK-3475) in KEYNOTE-001.
Authors: Jedd D. Wolchok, Omid Hamid, Antoni Ribas, Caroline Robert, Richard Kefford, Wen-Jen Hwu, Jeffrey S. Weber, Anthony M Joshua, Tara C. Gangadhar, Roxana Stefania Dronca, Adil Daud, Amita Patnaik, Richard Wayne Joseph, Hassane M. Zarour, Xiaoyun Nicole Li, Dahai Xue, Scot Ebbinghaus, Soonmo Peter Kang, Andrea Marie Perrone, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2015)

3000 Background: Immune-related response criteria (irRC) were developed to better characterize the atypical response patterns observed with ipilimumab. Previously, we showed that 7.2% of melanoma pts treated with the anti–PD-1 monoclonal antibody pembrolizumab also demonstrate atypical response patterns and that irRC may better represent the clinical benefit of pembrolizumab than conventional RECIST. This updated analysis includes all 655 melanoma pts enrolled in KEYNOTE-001 (NCT01295827). Methods: Pts received pembrolizumab 2 mg/kg every 3 wk (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W. Imaging was performed every 12 wk. Response was assessed centrally by irRC and RECIST v1.1. Investigator-assessed irRC was used for pt management. Early pseudoprogression was defined as ≥25% increase in tumor burden at first assessment that was not confirmed as progressive disease (PD) per irRC at the next assessment performed ~4 wk later. Delayed pseudoprogression was defined as ≥25% increase in tumor burden at any time point after the first assessment, followed by non-PD at the next assessment. Results: Of the 655 pts enrolled, 327 had ≥28 wk of follow-up by imaging at the time of analysis and were assessed for atypical responses. Overall, 29 pts (8.9%) experienced atypical response. Early pseudoprogression was observed in 15 (4.6%) pts. Late pseudoprogression was observed in 14 (4.3%) pts. In the 592 pts who survived ≥12 wk, 331 (56%) had best overall response of non-PD per RECIST and irRC, 177 (30%) had PD per both criteria, and 84 (14%) had PD per RECIST v1.1 but non-PD per irRC. OS was longer in pts with PD per RECIST but non-PD per irRC compared with those who had PD by both criteria (Table). Conclusions: Results of this expanded analysis are consistent with previous reports suggesting that pembrolizumab may result in atypical response patterns and that conventional response criteria may underestimate the therapeutic benefit of pembrolizumab in advanced melanoma. New standards such as irRC or irRECIST should be considered for assessing response to immunotherapy. Clinical trial information: NCT01295827. OS 12-mo Rate, % 24-mo Rate, % Non-PD by RECIST and irRC (n = 331) 92.1 77.6 PD by RECIST, non-PD irRC (n = 84) 74.4 37.5 PD by RECIST and irRC (n = 177) 33.5 17.3
A randomized study comparing etoposide and vindesine with or without cisplatin as induction therapy for small cell lung cancer
Authors: J.P. Sculier, J. Klastersky, P. Libert, P. Ravez, J. Thiriaux, J. Lecomte, G. Bureau, G. Vandermoten, G. Dabouis, J. Michel, J. Schmerber, R. Sergysels, D. Becquart, P. Mommen, M. Paesmans
Journal: Annals of Oncology (1990)

We conducted a randomized trial testing etoposide (120 mg/m2 d1-3) + vindesine (3 mg/m2 d1) with or without cisplatin (60 mg/m2 d1) in patients with SCLC. A total of 8 courses were given at 3-week intervals. 221 patients were registered and 201, 95 in the CEV arm and 106 in the EV arm, were eligible for survival analysis. 183 patients were evaluable for response: 74% had an objective response (OR) with CEV versus 55% with EV (p = 0.01). Complete response rates were, respectively, 21% and 13% (NS). In patients with limited disease (LD), OR rates were 72% and 61% (NS), and 76% and 48% in extensive disease (ED) (p = 0.01). There was no statistically significant difference in survival between the two regimens (p = 0.745, log rank test). Median survival for EV and CEV were, respectively, 40 and 45 weeks, and two-year survivals were 11% and 9%; in patients with LD, the corresponding figures were 14% and 16% (NS) and in those with ED, 8% and 3% (NS). Disease extent (LD vs ED), Karnofsky performance status and loss of body weight were significant prognostic factors for survival; age, sex, type of treatment and type of lesion were not. The CEV regimen was not significantly more myelotoxic than EV but was associated with more severe nausea, vomiting and alopecia. In conclusion, the addition of cisplatin to the EV regimen, a combination reported to be easily manageable, was associated with a significantly higher OR rate but survival was not significantly improved.