tbuckley/cabot-search huggingface dataset:
Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group.
Authors: F Mandelli, G De Rossi, P Mancini, A Alberti, A Cajozzo, F Grignani, P Leoni, V Liso, M Martelli, A Neri
Journal: Journal of Clinical Oncology (1987)

Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.
Aspirin use in prostate cancer and the risk of death and metastasis.
Authors: Jonathan Assayag, Laurent Azoulay, Hui Yin, Michael N. Pollak, Samy Suissa
Journal: Journal of Clinical Oncology (2013)

1518 Background: There has been recent interest in the role of aspirin in preventing prostate cancer outcomes, but data remain limited. The objective was to determine whether the use of aspirin after prostate cancer diagnosis is associated with a decreased risk of prostate cancer mortality, distant metastasis and all-cause mortality in men newly-diagnosed with prostate cancer. Methods: A population-based cohort of men diagnosed with non-metastatic prostate cancer between 01/04/1998 and 31/12/2009 was identified using the UK Clinical Practice Research Datalink, including the Cancer Registry. All men were followed until death, distant metastasis, or 01/10/2012. A nested case-control analysis was performed where, for each case with an incident outcome event, up to 10 controls were matched on age, year of diagnosis and duration of follow-up. Exposure was defined as aspirin use during the matched follow-up period. Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusted for covariates and considering effect modification by aspirin use prior to prostate cancer diagnosis. Results: The cohort included 13,396 prostate cancer patients, followed for 3.9 (SD=2.4) years during which 4,425 deaths occurred, including 2,315 from prostate cancer, and 2,344 cases of distant metastasis. Aspirin use was associated with an increased risk of prostate cancer mortality (RR 1.36, 95% CI 1.18-1.55) and all-cause mortality (RR 1.33, 95% CI 1.21-1.47), but not distant metastasis (RR 1.09, 95% CI 0.94-1.27). The increased risks were limited to patients who did not use aspirin before diagnosis, for both prostate cancer mortality (RR 1.69, 95% CI 1.43-2.00) and all-cause mortality (RR 1.62, 95% CI 1.44-1.82), while those who used aspirin before diagnosis did not have increased risks (RR 0.93, 95% CI 0.76-1.15 and RR 0.98, 95% CI 0.85-1.13, respectively). Conclusions: The use of aspirin after prostate cancer diagnosis is not associated with a decreased risk of prostate cancer outcomes. Although increased risks were observed for all-cause and prostate cancer mortality, these effects were exclusively driven by new-users of aspirin, suggesting that aspirin use in these patients was likely related to disease progression.
Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC): A planed 200-pt interim safety analysis of the NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG Intergroup Study (HECTOR).
Authors: W. Meier, W. Lichtenegger, C. Marth, A. J. Gonzalez-Martin, P. Harter, O. Tome, P. Wimberger, C. Kurzeder, G. Oskay-Özcelik, J. Sehouli
Journal: Journal of Clinical Oncology (2010)

5071 Background: We present the preliminary safety results from the phase III study of topotecan (T) plus carboplatin (C) versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC). While the primary endpoint of the study is PFS, the specific toxicity observed from these regimens is critically relevant. Therefore this planned safety analysis of the experimental arm (TC) and the standard therapy (control arm = CA) was conducted. Methods: From 02/07 to 12/09, 590 pts were screened and 550 pts were randomized to either T (0.75mg/m2/d1-3/q21d) + C (AUC 5/d1/q21d) or to standard therapy with CP or GC or PLDC based on patient preference. Results: The data from the first 200 pts were analyzed (Table). Median number of cycles was 6 (range 0-9) in the two arms. Most patients preferred the standard therapy with GC (78%) due to low alopecia rate since the PLDC arm was opened after the publication of CALYPSO date at the end of the global study. Hematological toxicity contributed to 41% of cycle delays in the CA and 36% in the TC arm. Neutropenia and infection rates were similar in both arms. G-CSF was administered more frequently to pts in CA arm (26%) than in TC arm (21%). Grade (G) > 2 nonhematological toxicity was not more frequent in the C-P arm. There were more severe adverse events (SAE) in the CA (66%) than in the TC arm (55%). Conclusions: This planned interim safety analysis on the first 200 patients confirmed the safety of the experimental arm and allowed to continue the study enrolment. Study recruitment was now completed in 12/2009. Toxicity Exp. arm% pts in the TC arm Control arm% pts in C-P arm Control arm% pts in C-G arm Anaemia G3-4 8.3 3.7 13.5 Thrombocytopenia G3-4 14.9 7.4 33.7 Alopecia G2 5.8 70.4 12.4 Neuropathy G>2 0.8 0 1.1 Allergic reactions G>2 3.3 7.4 5.6 Arthralgia/myalgia G>2 0 0 0 Hand- foot syndrome G>2 0.8 0 0 Mucositis G>2 0 0 0 Early treatment termination (toxicity related) 13.2 11.1 12.4 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Fresenius Biotech, GlaxoSmithKline, Medac
Abstract 18820: Bayesian Meta-Analysis of the Novel Oral Anticoagulants versus Warfarin in Patients With Renal Failure
Authors: Christopher Lang, Hye Gi Shim, Rohit Arora
Journal: Circulation (2013)

The novel oral anticoagulants (NOACS) dabigatran, rivaroxaban and apixaban for prevention of stroke and systemic embolization in atrial fibrillation are attractive alternatives to warfarin. Controversy exists regarding the use of these medication in renal failure. To compare differential benefit, we performed a Bayesian meta-analysis examining the efficacy and safety of the NOACS versus warfarin in patients with renal failure Methods: Using data from the 3 major trials investigating the novel oral anticoagulants, we conducted a Bayesian meta-analysis of patients stratified by creatinine clearance of 80 ml/min. The primary endpoints of stroke and systemic embolization were assessed, along with safety endpoints of major bleeding, if available. A Bayesian analysis was performed on each group, defining probabilities of benefit for the posterior probability. From this data, sequential Bayesian meta-analysis was performed and posterior probabilities were obtained. Results: Posterior probabilities for stroke and systemic embolization indicate that NOACS in patients with CrCl &gt;80 ml/min have an 74.8% probability of benefit over warfarin. In patients with CrCl 50-80 ml/min there is 95.5% probability of benefit. Patients with CrCl &lt;50 ml/min there is a 93.7% probability of benefit of NOACS over warfarin. Analysis of bleeding events using available data showed a trend towards benefit of NOACS versus warfarin in incidence of major bleeding events. Conclusions: The use of novel oral anticoagulants in patients with renal failure confers a high probability of benefit over warfarin in prevention of stroke and systemic embolization. The NOACS appear to have potentially improved bleeding outcomes in this subgroup, though data is limited. This analysis suggests that the novel oral anticoagulants are more effective and are at least as safe in patients with renal failure when compared with warfarin.
Effect of neoadjuvant systemic therapy prior to radical prostatectomy in high-risk prostate cancer on surgical morbidity: Contemporary results utilizing the Clavien System.
Authors: Stephen Bentley Williams, John W. Davis, Mary F. Achim, Amado J. Zurita, Surena F. Matin, Louis L. Pisters, John Francis Ward, Curtis Alvin Pettaway, Brian Francis Chapin
Journal: Journal of Clinical Oncology (2015)

66 Background: There is limited evidence definingthe morbidity of radical prostatectomy (RP) with curative intent for patients with high risk prostate cancer. Multimodality treatment for men with high risk prostate cancer using neoadjuvant systemic therapy followed by surgery is being increasingly explored. Methods: We analyzed 215 consecutive patients with high risk and very high risk prostate cancer who underwent robotic or open RP with extended pelvic lymph node dissection previously untreated or received neoadjuvant systemic therapy between 2006 and 2010 at a single tertiary care academic center. Univariable and multivariable logistic regression analyses were used to identify predictors of complications. Results: Baseline characteristics were similar between patients who underwent neoadjuvant systemic therapy followed by RP versus RP alone except for PSA (PSA&lt; or equal to 4 ng/ml: 75.4% vs. 15.5%, p&lt;0.001) and preoperative hemoglobin (13.8 g/dl vs. 14.4 g/dl, p=0.003), respectively. Twenty nine percent of patients (63 of 215 patients) experienced a complication of any grade ≤90 d after surgery 6% experienced Grade ≥3, with no significant difference between either cohort (p=0.50). On multivariate analysis, estimated blood loss [Odds Ratio (OR) 1.10; 95% CI, 1.0 to 1.2, p=0.03), length of stay (OR 1.75; 95% CI, 1.3 to 2.4, p=0.001) and preoperative hemoglobin (OR 0.71; 95% CI, 0.53 to 0.94, p=0.02) were independent predictors of the occurrence of any grade complication. Considering grade 3 or 4 complications, procedure time (OR 2.20; 95% CI 1.0 to 4.8, p=0.05) and estimated blood loss (OR 1.39; 95% CI, 0.98 to 1.96, p=0.06) were significant predictors of major complications. Conclusions: Postoperative morbidity in patients with high risk prostate cancer following RP with or without the use of neoadjuvant systemic therapy is comparable to contemporary RP series of low to intermediate risk disease reporting outcomes in a similar fashion. Use of neoadjuvant systemic therapy prior to RP was safe and did not appear to increase the risk of having a perioperative complication.
Systematic review of histamine type 2 receptor antagonists as an adjunct to curative surgical resection in gastrointestinal malignancies
Authors: S. Deva, M. B. Jameson
Journal: Journal of Clinical Oncology (2009)

e15085 Background: H 2 RAs have induced regression in a number of malignancies. The mechanisms that may contribute to this effect include inhibition of T-suppressor lymphocytes, increased tumor infiltrating lymphocytes and blockade of histamine-induced tumor proliferation and angiogenesis. Unique to cimetidine is its ability to inhibit vascular endothelial expression of the cell adhesion molecule E-selectin, to which many GI tumor cells adhere via carbohydrate antigen ligands. The optimal use of H2RAs in cancer patients could therefore be as adjuvant therapy rather than for metastatic disease. Methods: This systematic review examines the impact of H 2 RAs on the overall survival of patients when used as an adjunct to curative surgical resection for a GI malignancy. Using a sensitive search strategy, randomized controlled trials were identified in relevant databases. Criteria for study selection included: patients with colorectal or gastric cancer surgically resected with curative intent; H 2 RAs used i) at any dose, ii) for any length of time, iii) with any other treatment modality and iv) in the pre-, peri- or post-operative period. The results were stratified for both the type of malignancy and the H 2 RA used and analyzed by meta-analysis using Cochrane Collaboration software. Results: Of 350 trials identified, 8 were eligible for inclusion and had sufficient data for analysis, including a total of 1461 patients. Meta-analysis revealed a risk ratio for mortality of 0.86 (95% CI 0.76–0.99, p = 0.03) for patients randomised to H2RAs. Trials of colorectal cancer patients where cimetidine was the H2RA being evaluated demonstrated a significant survival advantage, risk ratio 0.53 (95% CI 0.33–0.84, p = 0.007). All other subgroups demonstrated a non-significant trend favouring H 2 RAs. Conclusions: H 2 RAs, and cimetidine in particular, appear to confer a survival benefit when given as an adjunct to curative surgical resection of GI cancers. The trial designs were heterogeneous and further large studies are warranted. No significant financial relationships to disclose.
Antitumor activity of PSMA ADC after progression on docetaxel in a mouse xenograft model of human prostate cancer
Authors: D. Ma, H. Zhang, B. Kennedy, T. Parsons, W. C. Olson
Journal: Journal of Clinical Oncology (2009)

3030 Background: Currently, there are no approved therapies for castration-resistant metastatic prostate cancer that has progressed following docetaxel therapy. Prostate-specific membrane antigen (PSMA) is an attractive target for antibody-targeted therapy of prostate cancer due to its abundant and restricted expression on the surface of prostate cancer cells. We have developed a novel antibody-drug conjugate (ADC) by linking a fully human PSMA monoclonal antibody to monomethylauristatin E (MMAE), a potent tubulin inhibitor. Here, we describe the use of PSMA ADC in a mouse model to treat xenografted human prostate tumors that have progressed following docetaxel therapy. Methods: Nude mice were implanted subcutaneously with 5 x 10 6 C4–2 human prostate cancer cells. Animals were first randomized to receive weekly intravenous (IV) doses of either 2 mg/kg docetaxel (n = 50) or vehicle (n = 10). Docetaxel significantly reduced tumor growth (p = 0.025) during the initial phase of the study; however, most of the tumors later progressed. When the tumor volume of an animal in the docetaxel group exceeded 400 mm 3 , the animal was rerandomized to receive continued docetaxel therapy (n = 18) or weekly IV doses of 6 mg/kg PSMA ADC (n = 18). Treatment effects were assessed by measuring tumor volume and overall survival. When tumor volume was assessed to be ≥2,000 mm 3 , animals would be sacrificed. Results: At 134 days following tumor implantation, the survival rate was 100% for animals in the PSMA ADC treatment group; 94% of these mice had tumor sizes &lt;100 mm 3 . In the continued docetaxel treatment group, 14 of 18 animals that were sacrificed when their tumors exceeded 2,000 mm 3 ; the survival rate was 22%. Therefore, PSMA ADC treatment significantly shrank tumors and increased overall survival of animals compared to continued docetaxel treatment (p &lt; 0.0001). Conclusions: PSMA ADC had antitumor activity in mice to xenografted human prostate tumors that had progressed following docetaxel treatment. Treatment with PSMA ADC significantly extended survival in this setting. [Table: see text]
Dissociative reactions to the San Francisco Bay Area earthquake of 1989
Authors: E Cardeña, D Spiegel
Journal: American Journal of Psychiatry (1993)

This study systematically evaluated the psychological reactions of a nonclinical population to the October 1989 earthquake in the San Francisco Bay Area.A representative group of about 100 graduate students from two different institutions in the Bay Area volunteered to participate in the study. Within 1 week of the earthquake, the authors administered a checklist of anxiety and dissociative symptoms to the subjects, and 4 months later they conducted a follow-up study with the same checklist.The participants reported significantly greater numbers and frequency of dissociative symptoms, including derealization and depersonalization, distortions of time, and alterations in cognition, memory and somatic sensations, during or shortly after the earthquake than after 4 months. To a lesser degree they also reported significantly more nonsomatic anxiety symptoms and Schneider's first-rank symptoms at the earlier testing time.These results suggest that among nonclinical populations, extreme distress may significantly increase the prevalence and severity of transient dissociative phenomena and anxiety. They provide further evidence of the role that dissociation plays in the response to trauma and are of considerable clinical and theoretical importance in view of the lifetime prevalence of traumatic experiences in the general population.
Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells
Authors: Wilson Kuswanto, Dalia Burzyn, Marisella Panduro, Kathy K. Wang, Young Charles Jang, Amy J. Wagers, Christophe Benoist, Diane Mathis
Journal: Immunity (2016)
Rate of antigen entry into the circulation in experimental versus naturally occurring immune complex glomerulonephritis.
Authors: L A Hebert, D J Birmingham, X P Shen, F G Cosio, A Fryczkowski
Journal: Journal of the American Society of Nephrology (1994)

This study tested the hypothesis that the rate of antigen entry into the circulation in systemic lupus erythematosus (SLE), a naturally occurring immune complex glomerulonephritis (IC-GN), is slow compared with that of traditional experimental models of IC-GN, in which the antigen is delivered rapidly as a daily iv bolus. This hypothesis was tested by comparing rates of decline of the third component of complement (C3) and of circulating neutrophils (PMN) in SLE patients with active disease with those of cynomolgus monkeys (CYN) undergoing induction of experimental IC-GN by means of a daily bolus infusion of antigen. It has previously been shown that, as antigen enters the circulation and forms circulating IC, C3 levels and circulating PMN decline acutely. Thus, acute changes in these parameters can be surrogates for the rate of antigen entry into the circulation. In the CYN undergoing induction of IC-GN (N = 11), infusion of the antigen (bovine gamma-globulin) over 10 min resulted in acute declines in C3 levels (25 +/- 6.6%; P = 0.0018 and PMN counts (59 +/- 9%; P < 0.0002). In addition, the CYN experienced the onset of acute respiratory distress and hypotension. By contrast, in patients with active SLE (N = 9), C3 and white blood cell counts measured at 24-h intervals did not change significantly, and episodes of acute hypotension or respiratory distress were not observed. In the CYN, the onset of visible vasculitic lesions in the omentum were also documented within minutes of the infusion of bovine gamma-globulin. The rapidity of onset of these vascular lesions suggests that the tempo at which lesions develop in experimental models of IC disease is faster than that of naturally occurring IC diseases. It was concluded that, in naturally occurring IC diseases, antigen probably enters the circulation slowly over prolonged periods of time, rather than as large boluses over short periods of time, as in traditional experimental models of IC-GN. Thus, models of IC-GN involving a daily bolus infusion of antigen may not be clinically relevant, particularly when IC clearing mechanisms are tested, because the efficiency of these mechanisms may be markedly influenced by the rate at which IC form in the circulation.
In Vivo Stabilization of a Gastrin-Releasing Peptide Receptor Antagonist Enhances PET Imaging and Radionuclide Therapy of Prostate Cancer in Preclinical Studies
Authors: Kristell L.S. Chatalic, Mark Konijnenberg, Julie Nonnekens, Erik de Blois, Sander Hoeben, Corrina de Ridder, Luc Brunel, Jean-Alain Fehrentz, Jean Martinez, Dik C. van Gent, Berthold A. Nock, Theodosia Maina, Wytske M. van Weerden, Marion de Jong
Journal: Theranostics (2015)

A single tool for early detection, accurate staging, and personalized treatment of prostate cancer (PCa) would be a major breakthrough in the field of PCa. Gastrin-releasing peptide receptor (GRPR) targeting peptides are promising probes for a theranostic approach for PCa overexpressing GRPR. However, the successful application of small peptides in a theranostic approach is often hampered by their fast in vivo degradation by proteolytic enzymes, such as neutral endopeptidase (NEP). Here we show for the first time that co-injection of a NEP inhibitor (phosphoramidon (PA)) can lead to an impressive enhancement of diagnostic sensitivity and therapeutic efficacy of the theranostic (68)Ga-/(177)Lu-JMV4168 GRPR-antagonist. Co-injection of PA (300 µg) led to stabilization of (177)Lu-JMV4168 in murine peripheral blood. In PC-3 tumor-bearing mice, PA co-injection led to a two-fold increase in tumor uptake of (68)Ga-/(177)Lu-JMV4168, 1 h after injection. In positron emission tomography (PET) imaging with (68)Ga-JMV4168, PA co-injection substantially enhanced PC-3 tumor signal intensity. Radionuclide therapy with (177)Lu-JMV4168 resulted in significant regression of PC-3 tumor size. Radionuclide therapy efficacy was confirmed by production of DNA double strand breaks, decreased cell proliferation and increased apoptosis. Increased survival rates were observed in mice treated with (177)Lu-JMV4168 plus PA as compared to those without PA. This data shows that co-injection of the enzyme inhibitor PA greatly enhances the theranostic potential of GRPR-radioantagonists for future application in PCa patients.
Bone Lesions in Cats With Anemia Induced by Feline Leukemia Virus2
Authors: Edward A. Hoover, Gary J. Kociba
Journal: JNCI Journal of the National Cancer Institute (1974)

Varying degrees of medullary osteosclerosis were in 12 of 13 cats with nonregenerative anemia induced by inoculation of feline leukemia virus (FeLV). In 7 cats with severe bone lesions, a trabecular network of cancellous bone extended from the primary spongiosum throughout the diaphysis and replaced the medullary marrow cavity. Despite the dramatic increase in medullary trabecular bone, histologic and ultrastructural examination of the bones indicated atrophy of osteoblasts and few osteoclasts, which implies general depression of bone growth and remodelling. C-type virus particles compatible with FeLV were associated with osteocytes, osteoblasts, and megakaryocytes, but not with other marrow cells.
O-019 SIRFLOX: Randomized trial comparing first-line mFOLFOX6 ± bevacizumab versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bevacizumab in patients with metastatic colorectal cancer (mCRC) – analysis by presence or absence of extra-hepatic metastases and bevacizumab treatment
Authors: G.A. van Hazel, V. Heinemann, N.K. Sharma, M.P.N. Findlay, J. Ricke, M. Peeters, D. Perez, B. Robinson, A. Strickland, T. Ferguson, J. Rodrigez, H. Kroening, I. Wolf, V. Ganju, E. Walpole, E. Boucher, T. Tichler, V. Gebski, M. Van Buskirk, P. Gibbs
Journal: Annals of Oncology (2015)
Mumps epidemic in Portugal despite high vaccine coverage - preliminary report
Authors: J A Dias, M Cordeiro, M A Afzal, M G Freitas, M. R. Morgado, J. L. Silva, L. M. Nunes, M. G. Lima, F Avilez
Journal: Eurosurveillance (1996)

A measles, mumps, and rubella (MMR) trivalent vaccine was added to Portugal's National Immunisation Programme (NIP) in 1987. All vaccines are given at health centres, free of charge, but an epidemic of mumps began in 1995, firstly in northern Portugal and