tbuckley/cabot-search huggingface dataset:
NC2213: a novel methionine aminopeptidase 2 inhibitor in human colon cancer HT29 cells
Authors: Ponniah Selvakumar, Ashakumary Lakshmikuttyamma, Umashankar Das, Hari N Pati, Jonathan R Dimmock, Rajendra K Sharma
Journal: Molecular Cancer (2009)

Methionine aminopeptidase 2 (MetAP2) is a bifunctional protein that plays a critical role in the regulation of post-translational processing and protein synthesis. MetAP2 is overexpressed in human colon cancer. In this report we screened various MetAP2 inhibitors and treated HT29 cells with various concentrations of compounds. We evaluated the expression of MetAP2 and pp60c-src expressions in HT29 cells. In addition we also carried out the cell proliferation and cell cycle analysis in the MetAP2 inhibitor-treated HT29 cells. The cell cycle analysis of HT29 treated with 1.0 microM of NC2213 showed an arrest in the G2 phase followed by an induction in the percentage of cells undergoing apoptosis in the sub-G1 phase. Western blot analysis revealed that the MetAP2 expression was dose-dependently decreased when the HT29 cells were treated with the 3,5-bis(benzylidene)-4-piperidone derivative (NC2213). In addition, phosphorylation of Src, a myristoylated oncoprotein was significantly decreased by 1.0 microM of NC2213 as revealed by Western blot analysis. Furthermore, NC2213 also inhibits the expression of pp60c-src in HT29 cells. Interestingly, this compound also inhibits the phosphorylation at Tyr416 of pp60c-src while increasing the phosphorylation at Tyr527 of pp60c-src. NC2213 inhibits the growth of HT29 cells by inducing apoptosis and might be useful for the treatment of human colon cancer.
Imaging in lung cancer: positron emission tomography scan
Authors: J.F. Vansteenkiste
Journal: European Respiratory Journal (2002)

In the past 5 yrs, positron emission tomography (PET), usually used with <sup>18</sup>F‐fluoro‐2‐deoxy-glucose (FDG), has become an important imaging modality in lung cancer patients. Currently, the use of FDG-PET in respiratory oncology is mainly for diagnosis and staging. Standard indications are the evaluation of an indeterminate solitary pulmonary nodule or mass, where FDG-PET has proven to be significantly more accurate than computed tomography (CT) in the distinction between benign and malignant lesions. Several studies have also convincingly demonstrated that locoregional lymph node staging by FDG-PET (in correlation with CT images) is significantly superior to CT, with a negative predictive value equal or even superior to mediastinoscopy. FDG-PET also improves extrathoracic staging, through the detection of lesions missed at conventional imaging or characterization of lesions that remain equivocal on conventional imaging. Many European countries now have or plan reimbursement in these indications. Large-scale randomized studies should now focus on the impact this accurate tumour imaging technique has on treatment outcome and cost-efficacy. Ongoing studies in specialized centres focus on the use of FDG-PET in more advanced clinical applications, such as planning radiotherapy, response evaluation after radiotherapy or (induction) chemotherapy, follow-up and early detection of recurrence, and prognostic information in this <i>in vivo</i> measurement of tumour glucose metabolism. After a short note on the technique used and a summary of the current common indications of diagnosis and staging, this paper will deal mainly with two of the more advanced clinical applications of FDG-PET in locally advanced nonsmall cell lung cancer: radiation treatment planning and assessment of induction chemotherapy. Finally, it should be mentioned that a whole new field of applications of positron emission tomography in molecular biology, using new radiopharmaceutical probes, is under extensive investigation. These techniques are promising for future use in very early response monitoring during chemo- or radiotherapy, in evaluation of novel molecular-targeted lung cancer therapies, or even gene therapy.
Failure of swimming exercise to improve capillarization in cardiac hypertrophy of renal hypertensive rats.
Authors: K Rakusan, P Wicker, M Abdul-Samad, B Healy, Z Turek
Journal: Circulation Research (1987)

Female Sprague-Dawley rats were made hypertensive by the two kidney/one clip Goldblatt procedure, while control animals were sham-operated. One week later, half of the animals were subjected to a moderate swimming exercise and the other half remained sedentary. Thus, four experimental groups, each consisting of 14 rats, were formed: control animals that were exercised or kept sedentary and corresponding renal hypertensive animals either exercised or sedentary. In hypertensive rats, a significantly increased left ventricular weight and reduced coronary reserve were found. Cardiac hypertrophy in hypertensive rats was characterized by a lower number of capillaries on a tissue cross-section, larger heterogeneity of the capillary net, and a less uniform orientation of capillaries in space. Total length of capillaries in the hypertrophic hearts increased significantly, but less than the increase in cardiac weight, resulting in reduced capillary length density. Chronic swimming for 2 hr/day for a period of 6 weeks, subsequent to a 4-week acclimation period, did not significantly influence any of the investigated indexes of capillaries from hypertrophic hearts. In the normotensive rats, chronic swimming resulted only in a moderate increase in total capillary length associated with a small increase in the left ventricular weight of similar degree. Thus, chronic exercise in normotensive rats induced a moderate increase in total capillary length per left ventricle, while it did not alleviate impaired capillarization of hypertrophic hearts from hypertensive rats.
Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study
Authors: Lauren C Harshman, Wanling Xie, Georg A Bjarnason, Jennifer J Knox, Mary MacKenzie, Lori Wood, Sandy Srinivas, Ulka N Vaishampayan, Min-Han Tan, Sun-Young Rha, Frede Donskov, Neeraj Agarwal, Christian Kollmannsberger, Scott North, Brian I Rini, Daniel YC Heng, Toni K Choueiri
Journal: The Lancet Oncology (2012)
New edicts for letters - Restrictions should not be imposed on post-publication peer review
Authors: Douglas G Altman
Journal: BMJ (2003)

Editor—I often read the short letters in newspapers and journals in preference to the long ones. They are simpler to assimilate, quicker to read, and often amusing too. But I know that the important stuff is generally in the longer letters.

Research published in scientific journals should be open to comment and correction in published correspondence.1 The BMJ has reduced its word limit for letters from 400 to 300 words (barely more than the length of the abstract of the paper one might be writing about), at the same time as Lancet reduced the time window from eight weeks to two.2,3

What next—a maximum of 800 words for research papers? More people would read them, I'm sure.

There is an effective “statute of limitations” in leading journals, whereby authors of papers are immune to disclosure of methodological weaknesses once some arbitrary (short) period has elapsed.4 Such time limits (four weeks at the BMJ ) discourage post-publication peer review. Similarly, one often cannot adequately address multiple and complex concerns about a study in a short letter.

Convenience should not take precedence over science. Brevity is not more important than scientific rigour. Editors are hiding behind arbitrary rules to avoid having to decide what is actually important. Such restrictions may be suitable for a magazine but not for a scientific journal.

I applaud the rapid responses on bmj.com. It is shocking that so few journals have followed suit. But, although it remains the case that only those published in the paper version get linked to the original article on PubMed, publication in the paper journal should not be determined by rules.

By all means encourage brevity and rapid submissions, but do not rule out longer or later publication if the circumstances warrant it. In particular, letters that draw attention to methodological flaws should not be time limited.4
Myocardial free-wall rupture after acute infarction: survival aided by percutaneous intraaortic balloon counterpulsation.
Authors: C Hochreiter, J Goldstein, J S Borer, T Tyberg, H L Goldberg, V Subramanian, I Rosenfeld
Journal: Circulation (1982)

After his first acute myocardial infarction, a 69-year-old male suffered the usually lethal complication of ventricular free-wall rupture. Early suspicion of possible rupture and immediate percutaneous insertion of an intraaortic balloon pump assist device afforded sufficient hemodynamic stability to proceed with cardiac catheterization. The diagnosis of ventricular free-wall rupture was confirmed and the extent of coronary artery disease defined. The patient underwent repair of the free-wall rupture and coronary artery bypass grafting and has returned to full activity.
Treatment of Respiratory Infection in Schoolboys with Phenethicillin
Authors: R. L. Vollum, B. E. Juel-Jensen
Journal: BMJ (1960)

An elevated level of serum vitamin B12 in chronic myeloid leukaemia, first reported by Beard et al. (1954), has been conclusively confirmed by a number of investigators.The exact cause of this elevated level is not clear.Lack of any differential pattern in the two groups-vegetarian or non-vegetarian-as revealed in the present study, indicates that in this disease the factor responsible for hypervitaminosis far outweighs the hypovitaminic effect of a vegetarian diet. SummaryThe serum vitamin B12 level was studied in 232 sub- jects (196 non-vegetarians and 46 vegetarians).The subjects belonged to the following five categories: normal, tropical eosinophilia, nutritional macrocytic anaemia, aplastic anaemia, and chronic myeloid leukaemia.Serum vitamin B12 in the vegetarian group was, in general, lower than that in the non-vegetarian group.Chronic myeloid leukaemia was an exception, all the patients in this category showing a raised level as previously reported.Low serum vitamin B12 was not, however, associated with any anaemia or neurological complications.The implications of these findings are discussed.
Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells
Authors: T Itagaki
Journal: Gut (2005)

Oxidative stress, including the generation of reactive oxygen species (ROS), is involved in hepatofibrogenesis. The authors' previous studies have shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates the activation of cultured rat hepatic stellate cells (HSCs), which possess oestrogen receptor subtype beta and are also activated by ROS.To define the mechanisms by which female sex hormones play an antifibrogenic role in activated HSCs, the effects of oestradiol and progesterone on ROS generation processes and intracellular pathways, leading to the activation of HSCs undergoing oxidative stress, was examined.HSCs, isolated from rats, were cultured for 7 days with oestradiol or progesterone for 24 hours as pretreatment, and oxidative stress was then induced by exposure to low doses of hydrogen peroxide for another 24 hours.Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced transforming growth factor-beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the activation of mitogen activated protein kinase (MAPK) pathways and transcription factors. Progesterone exerted a stimulatory effect through the progesterone receptor on the induction of ROS generation processes and intracellular pathways, resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were inhibited by oestradiol.These findings show for the first time that oestradiol inhibits the activation of transcription factors by suppressing ROS generation processes and the MAPK pathways, and inactivates the downstream transcription processes involved in TGF-beta1 expression and HSC activation, whereas progesterone acts in opposition to the favourable effects of oestradiol and its effects are blocked by oestradiol.
Chronic obstructive pulmonary disease * 6: The aetiology of exacerbations of chronic obstructive pulmonary disease
Authors: A J White
Journal: Thorax (2003)

Exacerbations of COPD are thought to be caused by interactions between host factors, bacteria, viruses, and changes in air quality to produce increased inflammation in the lower airway. The evidence for this and the potential mechanisms by which they result in the characteristic symptoms of exacerbations is reviewed. A better understanding of the causes and processes is needed for the appropriate use of existing treatments and the development of new ones. Future studies need to define populations clearly, stratify for known confounding factors, and should aim to identify clinical correlates so that clinical practice can be modified appropriately.
Safety and efficacy of erlotinib in first-relapse glioblastoma: a phase II open-label study
Authors: W. K. A. Yung, J. J. Vredenburgh, T. F. Cloughesy, P. Nghiemphu, B. Klencke, M. R. Gilbert, D. A. Reardon, M. D. Prados
Journal: Neuro-Oncology (2010)

Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is active in glioblastoma. We evaluated erlotinib efficacy in patients with first-relapse glioblastoma and assessed whether response was related to EGFR amplification and/or concomitant use of enzyme-inducing antiepileptic drugs (EIAEDs) in a phase II open-label study of glioblastoma patients in first relapse. Patients took erlotinib daily until progression. Starting dose was 150 mg for patients not taking EIAEDs and 300 mg for patients taking EIAEDs. Tumors were radiographically assessed every 8 weeks. Response was evaluated by investigators and confirmed by an independent radiology facility (IRF). The primary efficacy outcome was the objective response (OR) rate, according to the modified WHO criteria. Enrollment (n = 48) was terminated after a planned interim analysis due to an insufficient number of responses. The IRF confirmed 1 complete and 2 partial responses (PRs), for an OR rate of 6.3% (95% confidence interval [CI]: 1.7–17.0). Investigators determined 1 complete response and 3 PRs, median response duration of 7.0 months, 6-month progression-free survival (PFS) of 20% (95% CI: 10.0–32.4), and median survival of 9.7 months (95% CI: 5.9–11.6). Outcomes were not related to EGFR amplification or EIAED status. Diarrhea and rash were the most common adverse events (AEs); 23% of patients experienced grade 3–4 drug-related AEs. Despite the limited number of responses, 6-month PFS and median survival reached or exceeded the previously reported values for patients undergoing chemotherapy for recurrent glioblastoma. EGFR amplification was not associated with erlotinib activity. Given the large CIs and nonrandomized nature of the study, results should be interpreted cautiously.
Evidence for mast cell involvement in human postoperative ileus: a novel link
Authors: R. De Giorgio, G. Barbara
Journal: Gut (2007)

Postoperative ileus (POI) is defined as a severe impairment of gut motility which unavoidably follows any type of abdominal and, to a lesser extent, extra-abdominal surgery.1 2 Clinically, this condition is characterised by symptoms and signs of intestinal subocclusion including nausea, vomiting, lack of passage of flatus and stool, along with abdominal distension and absence of borborygmi. Although the clinical outcome is essentially not life-threatening, POI is a markedly morbid condition accompanied by increased hospitalisation (ie, up to 10 days or longer in the most severe cases)3 and related costs.4 The need to improve the patient’s postoperative course and reduce time spent in hospital has fuelled basic and clinical research aimed at a better understanding of the pathogenetic mechanisms involved in POI. Several potentially relevant factors, including extrinsic and intrinsic neural reflexes, a variety of inflammatory mediators and pharmacological agents used during postoperative analgesia, have been implicated in the pathogenesis of POI.2 5–7 The clinical evidence that patients undergoing minimally invasive (ie, laparoscopic) surgery have a shorter period of POI suggests that manipulation of bowel loops during surgery plays an important pathogenetic role in this condition.8 9

Data from animal models indicate that abdominal surgery and bowel manipulation promote cessation of gut motility by at least two major mechanisms: (1) activation of neural reflexes; and (2) a remarkable inflammatory response within the enteric neuromuscular layer.5–7 Concerning neurogenic mechanisms, the activation of inhibitory reflex circuits has been proposed to contribute to POI. These reflexes can occur at different levels of the innervation supplying the gut, namely within the intrinsic (enteric) nervous system or via extrinsic nerve pathways involving prevertebral ganglia, the spinal cord or supraspinal centres.5–7 Although the hierarchy and sequence of these reflexes remain a matter of …
Regional Changes in Hormone Therapy Use and Breast Cancer Incidence in California From 2001 to 2004
Authors: Anthony S. Robbins, Christina A. Clarke
Journal: Journal of Clinical Oncology (2007)

Recently, an unprecedented 1-year 7% decrease in the overall incidence of invasive female breast cancer in the United States was reported. It has been suggested that the decrease resulted from the mass cessation of estrogen-progestin hormone therapy (EPHT) in 2002. We took advantage of California's unique population-based cancer surveillance resources to assess whether regional changes in breast cancer incidence observed between 2001 and 2004 correlated with regional changes in EPHT use between 2001 and 2003.We obtained statewide cancer registry and California Health Interview Survey (CHIS) EPHT data for almost 3 million non-Hispanic white women age 45 to 74 years, residing in California's 58 counties. We examined trends in the age-adjusted incidence of invasive female breast cancer and compared these with trends in the use of EPHT, after grouping all California counties into three groups based on EPHT use in 2001. We also examined CHIS data on trends in screening mammography. Results In 2001, there were large regional differences in EPHT use and breast cancer incidence. From 2001 to 2004, incidence declined by 8.8% in the counties with the smallest EPHT reductions, by 13.9% in those with intermediate reductions, and by 22.6% in counties with the largest EPHT reductions. Between 2001 and 2003, CHIS data did not show any significant change in the proportion of women who reported having a mammogram in the previous 2 years.These data support the hypothesis that changes in EPHT use in 2002 may be responsible for significant declines in breast cancer incidence between 2002 and 2003 and sustained through 2004.
Functional Characterization of the Bladder Cancer Marker, BLCA-4
Authors: Thu-Suong Van Le, Julie Myers, Badrinath R. Konety, Timothy Barder, Robert H. Getzenberg
Journal: Clinical Cancer Research (2004)

Bladder cancer is a common disease of the genitourinary tract for which the development of a noninvasive detection technique would have a significant impact on disease management. One of our previously identified bladder cancer-specific proteins, BLCA-4, appears to be associated with a "field effect" of the disease, and in clinical trials is able to separate individuals with bladder cancer from those without the disease with high sensitivity and specificity. The potential clinical utility of this marker has led to the analysis of its function in bladder cancer pathobiology.To additionally analyze the specificity of this marker, the expression in the urine of a variety of benign urologic conditions was analyzed. After cloning the gene encoding BLCA-4, functional aspects of the protein were analyzed by overexpressing it in cell systems, as well as its interaction with other transcription factors and in gel mobility shift assays. Finally, to determine the timing of expression in relation to the observance of bladder cancer, an animal model of the disease was examined.Expression of BLCA-4, the cDNA of which reveals that it is a novel member of the ETS transcription factor family, is not found in benign urologic conditions. Overexpression leads to increased growth rates of cells, and the protein interacts with other transcription factors. In vivo studies reveal that BLCA-4 expression occurs significantly before the observance of grossly visible tumors in an animal model of the disease.BLCA-4 is a bladder cancer marker that is highly specific and occurs early in the development of the disease. It appears to be a transcription factor that may play a role in the regulation of the gene expression in bladder cancer. BLCA-4 is a marker with significant clinical utility that may have an active role in the disease.
No Place Like Home? Outpatient Management of Patients With Febrile Neutropenia and Low Risk
Authors: Alison G. Freifeld, Kent A. Sepkowitz
Journal: Journal of Clinical Oncology (2011)

and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: Proposal of new computed tomography response criteria. J Clin Oncol 25:1753-1759, 2007 45. Choi H, Charnsangavej C, de Castro Faria S, et al: CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: A quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 183:1619-1628, 2004 46. Lencioni R, Llovet JM: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52-60, 2010 47. Abou-Alfa GK, Schwartz L, Ricci S, et al: Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293-4300, 2006 48. Abou-Alfa GK, Zhao B, Capanu M, et al: Tumor necrosis as a correlate for response in subgroup of patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. ESMO 2008, Stockholm, Sweden. Ann Oncol 19:viii178, 2008 (suppl 8; abstr 547P)
Should NICE's threshold range for cost per QALY be raised? Yes
Authors: A. Towse
Journal: BMJ (2009)

NICE has recently raised the threshold for end of life drugs. <b>Adrian Towse</b> argues it should consider doing the same for other treatments, but <b>James Raftery</b> (doi:10.1136/bmj.b185) believes that the threshold is already too high
High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H
Authors: Claire E. Dearden, Estella Matutes, Bruno Cazin, Geir E. Tjønnfjord, Antonio Parreira, Benet Nomdedeu, Pietro Leoni, Fiona J. Clark, Deepti Radia, Saad M. B. Rassam, Tony Roques, Nicolas Ketterer, Vasantha Brito-Babapulle, Martin J. S. Dyer, Daniel Catovsky
Journal: Blood (2001)
Autoimmunity in a Cohort of 106 partial DiGeorge Syndrome Pediatric Patients
Authors: B. Tison, C.M. Davis, S.L. Abramson, I. Hanson, S. Nicolas, M.E. Paul, F. Seeborg, W.T. Shearer, M.D. Perez, L.M. Noroski
Journal: Journal of Allergy and Clinical Immunology (2011)