tbuckley/cabot-search huggingface dataset:
Long-Term Risk of Colorectal Cancer after Excision of Rectosigmoid Adenomas
Authors: Wendy S. Atkin, Basil C. Morson, Jack Cuzick
Journal: New England Journal of Medicine (1992)

Surveillance by repeated colonoscopy is currently recommended for patients with colorectal adenomas. We assessed the long-term risk of colorectal cancer after rigid-instrument sigmoidoscopy and polypectomy in 1618 patients with rectosigmoid adenomas (tumor of the rectum or distal sigmoid colon) who did not undergo surveillance. A total of 22,462 person-years of observation were accrued (mean, 14 years per patient).The incidence of subsequent rectal cancer in these patients was similar to that in the general population (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.7 to 2.1). Most rectal cancers developed in patients whose adenomas had been inadequately removed; the risk was very low after complete removal. The risk of subsequent colon cancer depended on the histologic type, size, and number of adenomas in the rectosigmoid. Among 842 patients with a rectosigmoid adenoma that was tubulovillous, villous, or large (greater than or equal to 1 cm), colon cancer developed in 31 patients. The standardized incidence ratio was 3.6 (95 percent confidence interval, 2.4 to 5.0) overall and 6.6 (95 percent confidence interval, 3.3 to 11.8) if there were multiple rectosigmoid adenomas. Among the remaining 776 patients with only small, tubular adenomas (whether single or multiple), colon cancer developed in only 4 patients. The standardized incidence ratio in this group was 0.5 (95 percent confidence interval, 0.1 to 1.3).Follow-up colonoscopic examinations may be warranted in patients with tubulovillous, villous, or large adenomas in the rectosigmoid, particularly if the adenomas are also multiple. In patients with only a single, small tubular adenoma that is only mildly or moderately dysplastic (43 percent of our series), however, surveillance may not be of value because the risk of cancer is so low.
Abstract 4663: Acquired resistance to gefitinib is associated with cancer stem-like phenotype and EMT in EGFR mutant lung adenocarcinoma.
Authors: Sun Min Lim, Hyun Jung Kim, Young Ho Ban, Sang Jun Ha, Byoung Chul Cho
Journal: Cancer Research (2013)

Abstract Background: Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of lung adenocarcinoma to tyrosine kinase inhibitor (TKI) such as gefitinib. During gefitinib treatment, however, the tumor becomes resistant by acquiring specific types of resistance via the somatic changes. Although the underlying mechanisms for acquired resistance include the amplification of c-Met gene and the secondary mutation in EGFR genes, there are still unknown mechanisms that cannot be explained by the two types of genetic changes. Here, we sought to find a novel mechanism to explain TKI-resistance of EGFR-dependent lung adenocarcinoma. Methods: We developed resistant cells (HCC827-GR) from gefitinib-sensitive HCC827 cells harboring EGFR deletion mutation by chronic exposure to increasing concentrations of gefitinib. Acquired resistance mechanisms of HCC827-GR cells were analyzed. Results: HCC827-GR showed much less phosphorylation of most receptor kinases including EGFR but higher phosphorylation of downstream signaling molecules, Erk and Akt, than its parental cell. By comparing the gene expression profiles between HCC827 and HCC827-GR, we found that cancer stem cell (CSC) markers, CD44 and ALDH1A1 genes, were highly induced in HCC827-GR compared with those in HCC827. Knockdown of CD44 and ALDH1A1 expression by RNA interference induced inactivation of both Akt and Erk phosphorylation in HCC827-GR. Furthermore, HCC827-GR displayed CSC-like functionality such as colony formation and the phenotype of epithelial-mesenchymal transition (EMT). Higher level of vimentin, ZEB1 and ZFHX4 and lower level of E-cadherin were observed in HCC827-GR together with morphological change. Interestingly, miR200c, a tumor suppressive microRNA, was dramatically decreased in HCC827-GR. Forced expression of miR200c in HCC827-GR abrogated the increased expression of ZEB1 and ALDH1A1, resulting in the restoration of E-cadherin. Conclusions: These findings imply that cancer stemness induced via CD44 and ALDH1A1 expression and EMT contribute to the acquisition of gefitinib resistance in EGFR-TKI sensitive lung adenocarcinoma. Therefore, CSC markers including CD44 and ALDH1A1 and EMT regulators such as miR200c can be used as therapeutic targets for TKI-resistant EGFR-dependent lung adenocarcinoma. Citation Format: Sun Min Lim, Hyun Jung Kim, Young Ho Ban, Sang Jun Ha, Byoung Chul Cho. Acquired resistance to gefitinib is associated with cancer stem-like phenotype and EMT in EGFR mutant lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4663. doi:10.1158/1538-7445.AM2013-4663 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Doctors' perceptions of drinking alcohol while on call: questionnaire survey
Authors: T. Ahmad
Journal: BMJ (2002)

We continue to find an effect of the Gulf conflict manifested as increased symptomatic distress.In our study, the modest increase in psychiatric disorders do no fully explain ill health in Gulf veterans.We thank the UK Ministry of Defence for help with tracing veterans, Graham Dunn for his expert advice and comments on the statistics, and the veterans who participated.
Ubiquitylation of Autophagy Receptor Optineurin by HACE1 Activates Selective Autophagy for Tumor Suppression
Authors: Zhengzhao Liu, Peng Chen, Hong Gao, Yu Gu, Jiao Yang, Hong Peng, Xingxing Xu, Haifeng Wang, Meiqiang Yang, Xiaoying Liu, Libin Fan, Shiyao Chen, Jian Zhou, Yihong Sun, Kangchen Ruan, Shuqun Cheng, Masaaki Komatsu, Eileen White, Lin Li, Hongbin Ji, Daniel Finley, Ronggui Hu
Journal: Cancer Cell (2014)
Abstract 1079: Identification of autocrine motility factor (AMF) receptor, HER2 (ErbB2) in breast cancer cells
Authors: Dhonghyo Kho
Journal: Cancer Research (2012)

Abstract Overexpression of HER2 (ErbB2) oncoprotein is associated with approximately 25% of aggressive breast carcinoma. Although a humanized monoclonal antibody (Trastuzumab) against HER2 is currently considered one of the most effective treatments, a significant number of patients are initially or eventually become resistant to Trastuzumab based therapy. Here, we demonstrate that secreted phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF), an orphan -CXXC- cytokine directly binds to HER2 and activates PI3K and MAPK through HER2 autophosphorylation, and also induces immediately HER2 cleavage in metalloprotease dependent fashion. We therefore speculate that AMF/HER2 signaling pathways play a physiological role in HER2 overexpressing breast cancer cells and contribute to Trastuzumab resistance and propose that AMF can be a novel therapeutic target in Trastuzumab resistant breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1079. doi:1538-7445.AM2012-1079
Sudden Death in Adolescents Resulting From the Inhalation of Typewriter Correction Fluid
Authors: Gregory S. King
Journal: JAMA (1985)

Inhalation abuse of various toxic agents continues to be a significant health problem among the younger segment of our society. We describe four cases of sudden death in adolescents associated with recreational sniffing of typewriter correction fluid occurring during the period 1979 through mid-1984. The solvents used in most of these fluids, 1,1,1-trichloroethane and trichloroethylene, are known to induce potentially fatal arrhythmias. Sniffing typewriter correction fluid poses a significant and underappreciated danger to the lives of these abusers. School health officials, public health departments, and law enforcement personnel should be alerted to the need for surveillance of this type of activity.
Flat-Topped and Condylomatous Papules in a Lung Transplant Patient
Authors: Fridolin Hoesly, Mark Cappel
Journal: JAMA Dermatology (2014)

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Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study
Authors: Smita Bhatia, Liton Francisco, Andrea Carter, Can-Lan Sun, K. Scott Baker, James G. Gurney, Philip B. McGlave, Auayporn Nademanee, Margaret O'Donnell, Norma K. C. Ramsay, Leslie L. Robison, David Snyder, Anthony Stein, Stephen J. Forman, Daniel J. Weisdorf
Journal: Blood (2007)
Resuscitation of Drowning Victims
Authors: James O. Elam
Journal: JAMA (1960)

Twenty-one successful users of oral resuscitation for victims of asphyxia were questioned to evaluate the acceptability and effectiveness of the method and the details of technique in the hands of laymen in the field. Vomiting and trismus occurred in 16 and 13 cases, respectively, and three patients had convulsions. Pallor or cyanosis was uniformly noted. Two patients, though successfully resuscitated temporarily, died subsequently. The six rescuers who were unhappy about the experience in retrospect rescued victims who either vomited or were drowned in sewage. Ten rescuers were not upset by the experience in retrospect, even though their patients vomited. The thumb-in-the-mouth technique, which had been extensively promoted in the area during the time of this survey, was attempted in only a few instances and was discontinued because the thumb was bitten in some cases.
Injectable Colloidal Gold for Use in Intrafractional 2D Image‐Guided Radiation Therapy
Authors: Rasmus I. Jølck, Jonas S. Rydhög, Anders N. Christensen, Anders E. Hansen, Linda M. Bruun, Henrik Schaarup‐Jensen, Asger Stevner von Wenck, Betina Børresen, Annemarie T. Kristensen, Mads H. Clausen, Andreas Kjær, Knut Conradsen, Rasmus Larsen, Per Munck af Rosenschöld, Thomas L. Andresen
Journal: Advanced Healthcare Materials (2015)

In the western world, approximately 50% of all cancer patients receive radiotherapy alone or in combination with surgery or chemotherapy. Image‐guided radiotherapy (IGRT) has in recent years been introduced to enhance precision of the delivery of radiation dose to tumor tissue. Fiducial markers are often inserted inside the tumor to improve IGRT precision and to enable monitoring of the tumor position during radiation therapy. In the present article, a liquid fiducial tissue marker is presented, which can be injected into tumor tissue using thin and flexible needles. The liquid fiducial has high radio‐opacity, which allows for marker‐based image guidance in 2D and 3D X‐ray imaging during radiation therapy. This is achieved by surface‐engineering gold nanoparticles to be highly compatible with a carbohydrate‐based gelation matrix. The new fiducial marker is investigated in mice where they are highly biocompatible and stable after implantation. To investigate the clinical potential, a study is conducted in a canine cancer patient with spontaneous developed solid tumor in which the marker is successfully injected and used to align and image‐guide radiation treatment of the canine patient. It is concluded that the new fiducial marker has highly interesting properties that warrant investigations in cancer patients.
Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome
Authors: Ercole Rao, Birgit Weiss, Maki Fukami, Andreas Rump, Beate Niesler, Annelyse Mertz, Koji Muroya, Gerhard Binder, Stefan Kirsch, Martina Winkelmann, Gabriele Nordsiek, Udo Heinrich, Martijn H. Breuning, Michael B. Ranke, André Rosenthal, Tsutomu Ogata, Gudrun A. Rappold
Journal: Nature Genetics (1997)
Clinical Features and Outcomes of Childhood Dilated Cardiomyopathy
Authors: Piers E. F. Daubeney, Alan W. Nugent, Patty Chondros, John B. Carlin, Steven D. Colan, Michael Cheung, Andrew M. Davis, C.W. Chow, Robert G. Weintraub
Journal: Circulation (2006)

Background— Despite considerable mortality, population-based prognostic factors for childhood dilated cardiomyopathy are lacking. Methods and Results— A population-based cohort study was undertaken of all children in Australia who presented with cardiomyopathy at age 0 to 10 years between January 1, 1987, and December 31, 1996. A single cardiologist analyzed all cardiac investigations, and a single pathologist analyzed histopathological material. There were 184 subjects with dilated cardiomyopathy. Positive viral identification or lymphocytic myocarditis was found in 30 (68.2%) of 44 cases with available early histology and 8 of 9 cases presenting with sudden death. Freedom from death or transplantation was 72% (95% CI, 65% to 78%) 1 year after presentation and 63% (95% CI, 55% to 70%) at 5 years. By proportional hazards regression analysis, risk factors for death or transplantation comprised age &gt;5 years at presentation (hazard ratio 5.6, 95% CI, 2.6 to 12.0), familial dilated cardiomyopathy (hazard ratio, 2.9; 95% CI, 1.5 to 5.6), lower initial fractional shortening z score (hazard ratio per z -score unit, 0.75; 95% CI, 0.65 to 0.87), and failure to increase fractional shortening z score during follow-up (hazard ratio per unit increase, 0.68; 95% CI, 0.58 to 0.79). At follow-up, 78 (44.6%) of 175 cases diagnosed during life have no symptoms and are not taking any cardiac medication. Conclusions— Early mortality is high in childhood dilated cardiomyopathy, but the clinical status of long-term survivors is good. This population-based study identifies children at risk of adverse events.
Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis
Authors: Masataka Sata, Akio Saiura, Atsushi Kunisato, Akihiro Tojo, Seiji Okada, Takeshi Tokuhisa, Hisamaru Hirai, Masatoshi Makuuchi, Yasunobu Hirata, Ryozo Nagai
Journal: Nature Medicine (2002)
Cerebral Perfusion Imaging with Technetium-99m HMPAO Following Cerebral Trauma
Authors: ROBERT H. REID, KAREN Y. GULENCHYN, JAMES R. BALLINGER, E C G VENTUREYRA
Journal: Clinical Nuclear Medicine (1990)

Thirteen patients with cerebral trauma were studied for cerebral perfusion by the use of Tc-99m HMPAO scanning. CT imaging was performed on nine patients. Because of their clinical condition, four patients were scanned only in the planar mode to help establish the diagnosis of brain death. Other indications for study included gunshot wound and blunt or sharp object trauma with or without skull fracture. In all cases, HMPAO scans showed defects with a quality equivalent to or greater than that demonstrated by CT. Our initial results suggest that HMPAO may predict the degree of permanent damage and which patients may develop post-traumatic headache. A diagnosis of brain death can be established without the withdrawal of medical therapy.
Cardiovascular Outcomes in Type 2 Diabetes: A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study
Authors: Robert S Elkeles, Judith R Diamond, Clare Poulter, Surinder Dhanjil, Andrew N Nicolaides, Shahid Mahmood, William Richmond, Hugh Mather, Patrick Sharp, Michael D Feher
Journal: Diabetes Care (1998)

OBJECTIVE To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)—clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)—were recorded. RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (−32 vs. 4%, P = 0.001), total cholesterol (−7 vs. −0.3%, P = 0.004), and total−to-HDL cholesterol ratio (−12 vs. −0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. −2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (−18 vs. −6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction. CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of “definite CHD events” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.
Abstract C61: A macrophage autonomous α4β1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth, and metastasis
Authors: Shweta Joshi, Alok Ranjan Singh, Muamera Zulcic, Bao Lei, Karen Messer, Donald L. Durden
Journal: Cancer Research (2013)

Abstract Macrophages, a major leukocyte population present in tumors, play an essential role in promoting tumor growth by affecting angiogenesis, immune suppression, invasion and metastasis. Despite considerable research efforts, the signal transduction events within macrophages which encode the complex cascade of events required for tumor growth and polarization of macrophages are poorly understood. Our previous findings demonstrate that α4β1 and αvβ3 integrin directed cell migration on specific extracellular matrices (ECM) requires a specific kinase-GTPase pair, Syk-Rac2. This pathway was shown to regulate the ECM dependent postnatal angiogenic response with no defect in vascular development. Herein, we have linked this ECM dependent signaling pathway in macrophages to the regulation of M2 macrophage differentiation and to the regulation of tumor growth, invasion and metastasis. Using mouse genetic models, we provide direct evidence that a macrophage specific, α4β1 integrin dependent Syk-Rac2 signaling axis acts in concert with the p110γ isoform (PTEN-PI-3 kinase pathway) to control HIF1α levels, tumor growth and metastasis. We report a novel proteasome/E3 ligase dependent mechanism by which PI-3 kinase regulates HIF1α levels under hypoxic conditions in the stromal compartment. Moreover, treatment with Syk or PI-3 kinase inhibitors demonstrate potent activity in multiple metastatic models. The results define a novel molecular mechanism for the regulation of HIF1α and a macrophage autonomous signaling pathway that is required for alterations in the ECM and the provisional integrin to regulate tumor metastasis and suggest treatment for metastatic disease targeting this pathway in the M2 macrophage compartment. Citation Format: Shweta Joshi, Alok Ranjan Singh, Muamera Zulcic, Bao Lei, Karen Messer, Donald L. Durden. A macrophage autonomous α4β1integrin-Syk-Rac2 signaling axis controls macrophage differentiation, tumor growth, and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C61.
Bronchopulmonary Kaposi's sarcoma in patients with AIDS.
Authors: D M Mitchell, M McCarty, J Fleming, F M Moss
Journal: Thorax (1992)

BACKGROUND: Kaposi9s sarcoma is the most common secondary neoplasm to complicate HIV infection and may cause pulmonary disease. METHODS: A prospective study was carried out in 140 consecutive patients who were HIV seropositive and required bronchoscopy for new respiratory symptoms of at least two weeks9 duration, with either a chest radiographic abnormality or abnormality of pulmonary function. The patients were classified into those with single local endobronchial lesions of Kaposi9s sarcoma or generalised widespread lesions. Before bronchoscopy all patients had routine simple pulmonary function tests and chest radiography. RESULTS: Thirty nine (21%) patients had evidence of cutaneous Kaposi9s sarcoma. Nineteen of the 39 were found to have endobronchial Kaposi9s sarcoma lesions at bronchoscopy, but none of those who did not have cutaneous Kaposi9s sarcoma. Respiratory symptoms of cough and breathlessness and radiographic abnormalities were attributed to Kaposi9s sarcoma in this group, except in four patients who had concomitant pneumocystis pneumonia. Eight patients had local endobronchial Kaposi9s sarcoma lesions and 11 had extensive lesions. Patients with extensive lesions had more widespread radiographic abnormalities; four of the patients with local endobronchial lesions had normal chest radiographs. All patients had reduced transfer factor for carbon monoxide and transfer coefficient, whereas patients with extensive endobronchial lesions also had reductions in forced expiratory volume in one second and forced vital capacity. Median survival (with palliative chemotherapy with vincristine and bleomycin) was only seven months. In three patients who needed further diagnostic bronchoscopy endobronchial lesions had regressed while they were having chemotherapy. CONCLUSIONS: This study suggests that endobronchial Kaposi9s sarcoma is a relatively common finding in patients with AIDS and is particularly common in patients with cutaneous Kaposi9s sarcoma who present with respiratory illness. Endobronchial Kaposi9s sarcoma causes respiratory disease and abnormalities of pulmonary function. Pulmonary Kaposi9s sarcoma should be considered as a possible cause for respiratory illness in any patient with cutaneous Kaposi9s sarcoma.