tbuckley/cabot-search huggingface dataset:
Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with a high-dose doxorubicin-containing regimen.
Authors: K S Zuckerman, A F LoBuglio, J A Reeves
Journal: Journal of Clinical Oncology (1990)

Forty-seven previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with four courses of a regimen that consisted of high-dose (120 mg/m2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine (2 mg), cytarabine (3 gm/m2), and dexamethasone (50 mg intravenously [IV] on day 1 and 20 mg/day orally on days 2 to 5) (AVAD), which was administered every 3 to 4 weeks. The median age of the patients was 58 years; 72% were Ann Arbor stage IV, 49% had "B" symptoms, 62% had masses larger than 7 cm, 40% had masses at least 10 cm in diameter, and 49% had serum lactate dehydrogenase (LDH) greater than 250 U/L. Overall, 72% of the patients (89% of diffuse large-cell lymphoma [DLCL] patients) attained complete (CR) or probable complete responses (PCR), and relapses occurred in 32%. There were no episodes of clinical congestive heart failure, but one patient developed recurrent ventricular arrhythmias. Fever during neutropenia occurred with 65% of treatment courses. Three deaths were attributed primarily to complications of therapy. The lymphoma-free survival of all entered patients is 51% (24 of 47), with a follow-up of 30 to 67 months (median, 58 months). These results confirm that high CR/PCR and long-term survival rates can be achieved in patients with aggressive histologies of non-Hodgkin's lymphomas, even in groups with poor prognostic factors, using high-dose anthracycline-containing chemotherapy regimens delivered over a short period of time. However, the apparently higher relapse rate in comparison to our previous study leads us to speculate that consolidation with noncross-resistant agents may be helpful in increasing even further the cure rate in this group of patients.
Early Effects of &lt;italic&gt;N,N&lt;/italic&gt;′-2,7-Fluorenylenebisacetamide on the Gastric Mucosa of the Rat
Authors: Helen M. Dyer, Kira K. Lueders, Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1967)

It has previously been reported that N,N′2,7-fluorenylenebisacetamide (2,7-FAA) fed in the diet at a concentration of 0.025% induced carcinomas and precancerous lesions of the glandular stomach of rats of the Buffalo strain. With the same experimental conditions, gastric studies have been made of rats of the same strain fed the diet with and without 0.025% 2,7-FAA. Body weight curves of these rats were identical to those in the previous carcinogenic studies. After 6–7 months, rats fed the carcinogen were showing signs of emaciation so the experiment was ended. The livers of the carcinogen-fed rats had hyperplastic nodules and a few hepatomas. The stomachs were small but otherwise appeared normal macroscopically, but histologic examination revealed atrophy of the mucosa. There were dilated glands deep in the gastric mucosa of the 2,7-FAA-fed animals examined, occasional dilated glands in the midzone filled with mucin, and increased mucin on the surface. Zymogen and acid cells were decreased. The amounts of gastric juice secreted during a 5-hour collection period were significantly less, the concentrations of mucin were slightly greater, and the free and total acid, and the peptic activity were less in the 2,7-FAA-fed rats than in the gastric juice of the control rats.
Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients.
Authors: B D Cheson, J M Sorensen, D A Vena, M J Montello, J A Barrett, E Damasio, M Tallman, L Annino, J Connors, B Coiffier, F Lauria
Journal: Journal of Clinical Oncology (1998)

PURPOSE To provide cladribine (CdA) to physicians for the treatment of patients with previously treated or untreated hairy cell leukemia (HCL), and to determine the response rate, response duration, survival, and toxicity with this agent. PATIENTS AND METHODS This Group C phase II study was open to all eligible patients whose primary physician obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 979 patients registered, 861 were assessable for response and 895 for toxicity. RESULTS The complete remission (CR) rate was 50% and the partial remission (PR) rate was 37%. At a median follow-up of 52 months, 12% of patients were reported to have progressed and 62 (7%) have died of disease. CONCLUSION This large experience confirms the excellent response rates and remission duration of CdA in patients with HCL. Nevertheless, the response rates in this setting, which approximates general clinical practice, were lower than in other series. In general, CdA was well tolerated, but the potential increased risk for secondary malignancies requires additional follow-up evaluation. CdA can now be considered as one of the best agents for the treatment of HCL.
geNorm assessment of the efficacy of novel reference genes ALG9, TFCP2 and ZNF410 compared to GAPDH for real time normalization in GI carcinoids
Authors: G. Eick, M. Kidd, S. Mane, B. Nadler, M. Champaneria, R. Pfragner, I. M. Modlin
Journal: Journal of Clinical Oncology (2006)

20052 Background: Robust quantitation of potential clinical marker genes using quantitative real-time PCR (Q RT-PCR) is critically dependent on accurate normalization. Although GAPDH has historically been used for normalization, its expression has been shown to vary widely between different tissues and experimental conditions. Additionally, conventional normalization strategies based on a single housekeeping gene can lead to large normalization errors. The determination of a panel of genes that have robust expression in the experimental system being studied is therefore essential to ensure accurate normalization and interpretation of results. Methods: Based upon the availability of large-scale gene databases, we developed methodology to identify highly expressed genes (mean log-transformed expression levels: 4–8 in all samples) with low variability (S.D. &lt; 0.22) in a Affymetrix U133A dataset of 36 gastrointestinal tumors and normal tissues. Eight novel candidate reference genes were identified and their expression levels established by Q RT-PCR in an independent set of GI tissue samples (n = 24). The geNorm tool was used to identify the most stably expressed set of genes amongst the 8 candidate genes. The expression levels of 3 potential GI tumor marker genes, namely the adhesin MAGE-D2, the metastasis-associated MTA1, and the mitosis regulator, NAP1L1, were normalized to GAPDH or geNorm and compared. Results: geNorm identified 3 genes, ALG9, TFCP2 and ZNF410, as the most robustly expressed control genes. GAPDH, in contrast, exhibited the highest variability and was considered the least stable gene of the nine evaluated. Two previously-identified target genes, MAGE-D2 and MTA1, were significantly elevated (p &lt; 0.05) in malignant tumor samples (vs normal GI samples) when normalized by geNorm ATZ but not when normalized using GAPDH. NAP1L1 was only over-expressed in small intestinal carcinoids (normalized to geNorm ATZ ). Expression levels of this gene were high in normal gastric mucosa. Conclusions: We provide a robust basis for the establishment of a reference gene set using GeneChip data and provide evidence for the clinical utility of identifying reference genes using the geNorm approach in GI neuroendocrine tumors. No significant financial relationships to disclose.
The determinants of recent gains in cancer survival: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
Authors: E. Sun, D. Lakdawalla, C. Reyes, D. Goldman, T. Philipson, A. Jena
Journal: Journal of Clinical Oncology (2008)

6616 Background: Although cancer remains a leading cause of death, the last few decades have seen improvements in the diagnosis and treatment of the disease. We measure the gains in cancer survival over the last 20 years, and separate these gains into the portions due to improvements in treatment and detection. Methods: We used data from the Surveillance, Epidemiology, and End Results database to calculate cancer survival over time. Our analysis focused on improvements in survival for non-Hodgkin's Lymphoma (NHL), breast cancer, colon cancer, pancreatic cancer, lung cancer, and all cancers combined. Due to data limitations, we calculated survival gains between 1990 and 2000 for NHL, lung cancer, and all cancers combined, and gains between 1980 and 2000 for the remaining cancers. To separate these gains into the portions due to improvements in treatment and detection, we applied the tumor stage data in SEER, which allows us to calculate survival conditional on stage of diagnosis. Since improvements in detection shift the distribution of patients into earlier stages, any improvements in survival conditional on diagnosis at a particular stage are likely to be due to advances in treatment, rather than detection. This empirical approach allows us to separate survival gains into the portions due to improved treatment and detection. Results: We observed large gains in survival during this time period, and most of the gains appear to have been driven by improvements in treatment. The table below summarizes our results. *1990 to 2000. Conclusions: In the past decades, gains in cancer survival have been largely driven by improvements in treatment, even for some cancers (breast and colon) for which there have been increased efforts to improve detection. In these latter cases, the results are attributable to both progress in detection and the surprisingly rapid improvement in survival at every given stage of diagnosis. Cancer Gain in Life Expectancy 1980–2000 (Years) Gain Due to Improved Treatment (%) All* 2.9–3.0 379–86% Breast 5.9–6.0 90–93% Colon 2.8–3.2 65–75% Lung * 0.4–0.5 81–91% NHL* 3.1–3.6 91–98% NHL (Aggressive) * 2.8–3.3 95–100% NHL (Indolent) * 3.6–4.8 95–100% Pancreatic 0.6 71% Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc.
Analyzing the same data in two ways: a demonstration model to illustrate the reporting and misreporting of clinical trials.
Authors: J Baar, I Tannock
Journal: Journal of Clinical Oncology (1989)

The methods used to analyze and interpret clinical trials of chemotherapy may have a major impact on the conclusions that are drawn in papers reporting them. To illustrate this problem, we constructed a hypothetical clinical trial in which patients with metastatic cancer were treated with chemotherapy. The following two articles provide reports of this trial, analyzed by methods that we would interpret as being of low and high quality, respectively. In the present report, we describe briefly the methodological differences that led to the opposite conclusions based on this single set of data. The errors of reporting and omissions of the first article (A) are similar to those that have been extracted from recent issues of the Journal of Clinical Oncology and other leading cancer journals, although they have not all appeared within a single report. This demonstration model illustrates problems in the reporting of clinical trials and suggests guidelines for improved reporting.
The burden of obstructive lung disease (BOLD) methodology overestimates the prevalence of COPD: A 5-year follow-up study
Authors: Brian Allwood, Rencia Gillespie, Mary Bateman, Helena Olckers, Luis Taborda-Barata, Greg Calligaro, Richard Van Zyl-Smit, Nulda Beyers, Eric Bateman
Journal: European Respiratory Journal (2014)

BACKGROUND:   The BOLD method (questionnaires and standardized post-bronchodilator spirometry) estimates and compares the prevalence of COPD in different countries. Its diagnostic accuracy has not been fully evaluated.   AIM:   To assess the diagnostic accuracy of the BOLD methodology.   METHODS:   We performed a BOLD assessment, additional lung function and clinical assessment in subjects 5 years after their COPD diagnosis in the Cape Town BOLD study in 2005.   RESULTS:   The response rate was 56% (106 of 196 eligible subjects). Sixteen subjects (15%) had a post-bronchodilator FEV1:FVC≥0.7 (i.e. non-obstructed), a further 11 subjects (10%) were non-obstructed using lower limit of normal (7 of whom were >70yr). Using 2 sets of clinical criteria of different stringency to define asthma, 10 or 18% of the cohort were considered to have asthma: 6 or13% without current airflow limitation (AFL); 11 or19% with current AFL (n=90); and 10 or26% with both AFL and reversibility (n=31). In a same-day comparison between the BOLD handheld (ndd EasyOne) and office spirometry (nSpire), the FEV1 differed by >150ml in 23%, resulting in reclassification of COPD status in 17% of subjects [Bland-Altman: mean diff=41ml;sd 146ml; 95%CI: -250:+333ml]. Between visit variability of the ndd EasyOne (performed 150ml between visits. [mean diff=18ml;sd 220ml; 95%CI: -0.422:+0.458ml].   CONCLUSIONS:   The BOLD methods overestimate the burden of COPD owing to use of the fixed FEV1/FVC definition, lack of discrimination from asthma, and test variability of the handheld spirometer.
The effects of prior radiation therapy and age on the frequency and duration of complete remission among various four-drug treatments for advanced Hodgkin's disease.
Authors: M R Cooper, T F Pajak, A J Gottlieb, A S Glicksman, N Nissen, F Richards, C Bloomfield, J F Holland
Journal: Journal of Clinical Oncology (1984)

The current report examines the clinical response observed in 137 patients with advanced Hodgkin's disease who had relapsed from an initial complete response following radiation therapy (RTF) in comparison to 280 patients with no prior therapy (NPT). Patients were prospectively randomized to therapy with a four-drug combination chemotherapy program to determine whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine when combined with procarbazine and prednisone. The frequency of complete remission (CR) was 75% for the RTF group compared to 60% of those with NPT (P = .005). In the RTF group, those patients receiving a nitrosourea (CCNU) had a significantly greater CR frequency than those receiving mechlorethamine (P = .006). Significant risk factors favoring longer duration of remission were age less than 40 (P = .005), the absence of splenic involvement (P = .007), and the use of CCNU-containing programs (P = .015). The advantage for CCNU-containing programs was seen only in patients less than 40 years of age. In this study, the strongest factors favorably affecting response to therapy were prior RTF, age less than 40 years, and treatment with a nitrosourea (CCNU).
Posterior capsule opacification 1 1The following two letters address an article that appeared in the March 2001 issue of the Journal:Apple DJ, Peng Q, Visessok N, et al. Eradication of posterior capsule opacification: documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 psuedophakic human eyes obtained postmortem. (Ophthalmology 2001;108:505–18.)
Authors: John F Ramsey
Journal: Ophthalmology (2002)
Impact of alfa delta sleep, but not obstructive sleep apneas on potential cardiotoxic CD4 lymphocytes
Authors: Richard Staats, Raquel Rodrigues, Aguiar Margarida, Fernandes Dina, Moreira Susana, Valença João, Barbara Cristina, Bugalho António, Moita Luís
Journal: European Respiratory Journal (2013)

Introduction:  Obstructive sleep apneas (OSA) are known to affect immune functions, but the role of sleep patterns like the alpha delta sleep (AD-sleep) have not been addressed. Perforin (P) and/or granzyme-B (GrB) positive CD4 lymphocytes (CD4+) have been linked to the instability of atherosclerotic plaques. Here we report preliminary results suggesting that alpha-delta sleep and not OSA affect cytotoxic CD4+ T cells.  Methods:  80 participants were included. According to the apnea/hypopnea index (AHI) groups were classified as controls (C=AHI  15/h). AD-sleep was defined as > 40% of slow wave sleep with superimposed alpha-rhythm. Intracellular P and GrB in CD3+CD4+ lymphocytes were investigated by standard flow cytometry analysis. Results are shown as means +/- SEM. A p  Results:  Age and BMI were similar between the 4 groups. Table 1 shows the main results.  Discussion:  To our knowledge this is the first study to report an influence of AD sleep on cytotoxic lymphocytes. While CD4+ cells have limited cytotoxic potential, they might be important in coronary heart disease and viral defense. AD sleep is common in patients with non-restoring sleep like fibromyalgia or chronic fatigue (CF). Our results might help understanding why patients with a CF show a reduced cytotoxic response. An impact of OSA on these cells was not confirmed.This work was supported by Fundacao e a Tecnologia PIC/IC/82991/2007.
PTU-236 Surgical site infection (SSI) rates in colorectal surgery: room for improvement: Abstract PTU-236 Table 1
Authors: J Docherty
Journal: Gut (2015)

<h3>Introduction</h3> SSI in colorectal surgery is a major cause of morbidity and is poorly recorded in clinical practice. We had a high rate of wound infection in our unit and therefore over a four year period we worked as a multidisciplinary group which included colorectal surgeons, infection control / surveillance nurses, microbiologists, theatre nurses and ward nurses to reduce our SSI rate in major elective colorectal surgery. We envisaged that we could reduce our wound infection rate but recognised that deep and organ space infection would remain unchanged, as these are related to anastomotic failure, which would not be altered by this work. Our aim, therefore, was to use quality improvement methodology to change our SSI rates. <h3>Method</h3> We formed a core team –the collaborative who met monthly. Using the model for improvement we set an aim- to reduce colorectal SSI in elective patients by 50% by June 2014. We looked at the evidence to determine changes we would make and we collected data weekly on all elective colorectal patients. Independent to the surgical team, infection surveillance staff monitored colorectal patients’ wounds and identified patients with in hospital and readmission wound infections, within 30 days of surgery (using standard national definitions of SSI). Based on the available evidence we introduced several changes over this quality improvement project: designed dedicated data collection forms written pre-op advice to patients clippers used for immediate hair removal changed to 2% chlorhexedine skin preparation introduced specific closing trays and limited redraping standardised wound dressing and its management, reviewed prophylactic antibiotic cover standardised prophylactic antibiotics and ensured repeat administration in long procedures and where there was excessive blood loss ensured tight glyacemic control in diabetic patients and strove for normothermia Using the model for improvement ensured reliability of all of our processes in the work detailed above and enabled us to maintain success <h3>Results</h3> Three of the four consultant colorectal surgeons were in post for the whole time period and all of their major elective colorectal patients are included. For the calendar years 2012 to 2014 our collective infection rates are shown in the Table 1. We achieved our aim of reducing colorectal SSI by 50%. <h3>Conclusion</h3> By engaging the multidisciplinary team and explaining what we wanted to achieve; we were able to consistently apply the evidence base and substantially lower wound infection rates in elective colorectal surgery. Our next priority in this work is ensure that all of the processes underpinning this reduction are reliable and will continue in perpetuity. <h3>Disclosure of interest</h3> None Declared.
Activation of a Plasma Membrane–Associated Neutral Sphingomyelinase and Concomitant Ceramide Accumulation During IgG-Dependent Phagocytosis in Human Polymorphonuclear Leukocytes
Authors: Vania Hinkovska-Galcheva, Lars Kjeldsen, Pamela J. Mansfield, Laurence A. Boxer, James A. Shayman, Suzanne J. Suchard
Journal: Blood (1998)
Phase I/II trial of OncoVEX<sup>GM-CSF</sup> combined with radical chemoradiation (CRT) in patients with newly diagnosed node-positive stage III/IV head and neck cancer (HNC)
Authors: R. S. Coffin, M. Hingorani, I. McNeish, A. Sibtain, B. Hamilton, C. Love, C. Nutting, K. Harrington
Journal: Journal of Clinical Oncology (2007)

14095 Background: OncoVEX GM-CSF is a second generation oncolytic herpes virus expressing GM-CSF which has previously completed a Phase I study with evidence of anti-tumor activity. Combination of OncoVEX GM-CSF with CRT has additionally demonstrated significant pre-clinical anti-tumor activity. Methods: Patients (pts) with newly-diagnosed node-positive stage III/IV HNC were enrolled in cohorts of 4. Patients received radiotherapy (70 Gy/35 fractions to gross disease, 50 Gy/25 fractions to elective areas) with concomitant cisplatin (100mg/m 2 days 1, 22, 43). Four doses of intranodal virus were given on days 1, 22, 43 and 64 as follows: Cohort 1 - 10 6 , 10 6 , 10 6 , 10 6 ; Cohort 2 -10 6 , 10 7 , 10 7 , 10 7 ; Cohort 3 - 10 6 , 10 8 , 10 8 , 10 8 pfu/ml. Patients underwent neck dissection 4–6 weeks after the last dose. Endpoints were safety, viral replication and anti-tumor activity. Results: Eight pts have completed the protocol. Nodal stages were N2a (2 pts), N2b (3), N2c (2), N3 (1). Compliance with the CRT schedule was 100%. In Cohort 1, 1 pt received only 3 doses of virus because of early complete response (CR). In Cohort 2, 1 pt received 3 doses and 1 pt 2 received doses because of early CR. Neck dissection was undertaken as planned in all but 1 pt. CRT-related toxicities were not exacerbated by OncoVEX GM-CSF . Non-CRT-related toxicities were mild (grade 1–2 fever and injection site pain). No dose-limiting toxicities were seen. In pts in whom nodal biopsy was possible during treatment, evidence of viral replication was seen. Clinical responses in the primary site (7 pts) and nodal disease (8 pts) were impressive which anecdotally appeared to be greater than would be expected with chemoradiation alone. Pathological CR was confirmed at the primary tumour site in 6 pts and in the neck in 3 pts after neck dissection. Extensive tumour necrosis was seen in all injected nodes. Extensive staining for OncoVEX was also seen including in adjacent uninjected nodes demonstrating considerable intratumoral virus spread. Conclusions: Combination of OncoVEX GM-CSF and CRT is well tolerated with promising anti- tumor activity. Recruitment to the final dose-escalation cohort has now been completed. No significant financial relationships to disclose.
Pathophysiologic Features and Prevention of Human and Experimental Acute Tubular Necrosis
Authors: NORBERT LAMEIRE, RAYMOND VANHOLDER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Acute renal failure (ARF) remains a common and potentially devastating disorder that affects as many as 5% of all hospitalized patients, with a higher prevalence in patients in critical care units. The focus of this article is on categorizing recent pathophysiologic and clinically relevant developments in the field. The vascular and tubular factors in the pathogenesis of ARF, together with the potential mechanisms of recovery and repair of the injured kidney, are discussed. A number of experimental and clinical interventions to prevent. ARF are summarized. Although the clinical treatment of these patients is still largely supportive and many recent clinical trials showed rather negative results, it is hoped that basic research will provide therapeutic tools to improve the grim prognosis of this disease in the future.