tbuckley/cabot-search huggingface dataset:
Whole-Genome Allelotyping Identified Distinct Loss-of-Heterozygosity Patterns in Mucinous Ovarian and Appendiceal Carcinomas
Authors: Colleen M. Feltmate, Kenneth R. Lee, Michael Johnson, John O. Schorge, Kwong-kwok Wong, Ke Hao, William R. Welch, Debra A. Bell, Ross S. Berkowitz, Samuel C. Mok
Journal: Clinical Cancer Research (2005)

Mucinous adenocarcinoma of the ovary is one of the common histologic types of ovarian cancer. Its pathogenesis is largely unknown. In addition, the differential diagnosis of metastatic mucinous carcinomas to the ovaries, particularly those originating from the appendix, remains challenging. The purpose of this study is to identify molecular biomarkers for mucinous ovarian adenocarcinoma and compare them with those of appendiceal origin.Genome-wide loss-of-heterozygosity (LOH) analysis was done on DNA isolated from 28 microdissected primary mucinous ovarian carcinomas and five appendiceal adenocarcinomas. Markers from high-loss regions were selected for further analysis on a total of 32 ovarian and 14 appendiceal cancers.High levels of LOH rates (>40%) were detected on chromosome arms 9p, 17p, and 21q in mucinous ovarian carcinoma cases. The frequency of allelic loss was similar between high-grade and low-grade mucinous ovarian carcinoma cases but was significantly higher in ovarian versus appendiceal cases. In addition, LOH rates on five chromosomal loci were statistically different between ovarian and appendiceal carcinomas.A high frequency of LOH can be found in mucinous ovarian adenocarcinomas independent of grade. Despite histologic similarities between mucinous ovarian carcinomas and metastatic appendiceal carcinomas, they have distinct LOH profiles, which may be used for distinguishing the two diseases.
Inclusion of end-of-life care in the global health agenda
Authors: Richard Harding, Irene J Higginson
Journal: The Lancet Global Health (2014)

Global development, strengthening of health systems, and an increase in access to treatments will improve health outcomes. However, the global need for palliative and end-of-life care will persist. As populations age and societies industrialise, the number of people who will need palliative care to manage the problems associated with chronic progressive illness, e specially cancer, are predicted to increase in low-income and middleincome countries. This increase is compounded by late presentation to medical services and restricted access to potentially curative options. The provision of palliative and end-of-life care, including access to pain relief, is a worldwide human right within existing covenants. 1 However, three documents have shown the woefully inadequate coverage in most regions. First, a worldwide classifi cation of every country’s level of palliative care provisions showed that only 58% of countries have a palliative care service, and provision ratios are as poor as one service per 90 million population. 2 Second, WHO’s 2014 global atlas of palliative care reported that less than 10% of the 20 million people every year who need palliative care at the end of life actually receive it, and although most care is delivered in high-income countries, 80% of people who need palliative care are in low-income and middleincome countries. 3
An asymptomatic male with mediastinal masses
Authors: K-A. Wu, W-C. Perng, S-C. Lee, M-F. Cheng, L-F. Sheu, C-P. Wu
Journal: European Respiratory Journal (2006)

A 35-yr-old obese male was admitted to the Tri-Service General Hospital (Taipei, Taiwan) for further examination of an abnormal opacity seen on a chest radiograph obtained during a medical check-up.The patient had been asymptomatic and had never received any treatment with steroids.Physical examination was unremarkable.Laboratory data, including complete blood count and tumour markers, were within normal limits.Abnormal laboratory findings from serological test were as follows: cholesterol 225 mg?dL -1 ; aspartate aminotransferase 45 IU?L -1 ; and alanine aminotransferase 61 IU?L -1 .The initial chest radiograph and computed tomography (CT) scan are seen in figures 1 and 2, respectively.The patient underwent mass resection via sternotomy.An oversized tumoural thymus (the first specimen) was resected in toto.However, the resected tumour was not comparable in size to the lesion discovered on CT imaging.A decision was made to incise the mediastinal pleura for confirmation of the pre-operative CT findings.A sizeable, whitish soft mass (the second specimen) was uncovered in the mediastinum, adjacent to the aortic arch.No attachment was found between the tumour and either the bronchial tree or oesophagus.Surgical excision of the tumour was performed.The histological findings of both specimens are shown in figures 3 and 4.
Colour-Blindness Amongst the Medical Profession
Authors: B. J. Jeffries
Journal: BMJ (1880)

4uly3,X8S.] 2(WEI BIT-ISH.'MEDIC>ALJ,OEIRN4____ing it, the tubes passed through the mouth might be used, even in the latter case, tot gin time)to allow auindpe'rative sugo tiao i* called.The tubes must necessarily be of various sizes, so as to suit the various larynges into-which they may-he intro u,ced..At -presert,.-atube, of a 'better shape and form than that now in use, ahadone which-w'll present other advantagea, is being prepared for me.It must be obvibus that the time during which the tubes are-retained must depend on the case.In some, a few hours might be sufficient to dispel the edema; in others, a much longer period is necessary.How to recognise that the instrument is in thie Trachea.-How would one recognise the presence of the instrument in the trachea ?i.By finding the instrument pass over the first ring or two of the trachea; 2. By finding that the air flows into the tube during inspiration and out during expiration-the opposite being the case if it be in the cesopha.gus; 3.By the mucous expectoration being'expelled from it; 4. By the negative signs that it is not in the oesophagus or stomrch--i.e., blowing up the stomach through the tube, etc.Before introdnci-sg the tubes, an examination by the laryngoscope ought to be made to ascertain the pre- cise state of the parts.Deductions.-The practical deductions which may be drawn, tenta- tively at least, from these cases are as follows.I. Tubes may be passed through the mouth into the trachea not only in chronic, but also in acute affections-such as cedema glottidis.2. They can be introduced without placing the patient under an anaesthetic.3. The respirations can be perfectly carried on through them.4. The expectoration can be expelled through them. 5. Deglutition can be carried on during the time the tube is in the trachea.6. Though the patient at first suffers -from a painful sensation, yet this passes off, and the parts soon become tolerant of the presence of the tube.7. The patient can sleep with the tube in situ.8.The tubes, in these cases at least, were harmless.. 9.The ultimate results were rapid, complete, and satisfactory.IO.Such tubes may be introduced in operations.on the face and mouth, in order to prevent blood from gaining access to the trachea, and for the purpose of administrating the anaesthetic; and they answer this purpose admirably.
Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model
Authors: Peter von Dadelszen, Beth Payne, Jing Li, J Mark Ansermino, Fiona Broughton Pipkin, Anne-Marie Côté, M Joanne Douglas, Andrée Gruslin, Jennifer A Hutcheon, KS Joseph, Phillipa M Kyle, Tang Lee, Pamela Loughna, Jennifer M Menzies, Mario Merialdi, Alexandra L Millman, M Peter Moore, Jean-Marie Moutquin, Annie B Ouellet, Graeme N Smith, James J Walker, Keith R Walley, Barry N Walters, Mariana Widmer, Shoo K Lee, James A Russell, Laura A Magee
Journal: The Lancet (2010)
PRSS3 promotes tumour growth and metastasis of human pancreatic cancer
Authors: G. Jiang, F. Cao, G. Ren, D. Gao, V. Bhakta, Y. Zhang, H. Cao, Z. Dong, W. Zang, S. Zhang, H. H. Wong, C. Hiley, T. Crnogorac-Jurcevic, N. R. Lemoine, Y. Wang
Journal: Gut (2010)

<h3>Background and aims</h3> Metastasis accounts for the poor outcome of patients with pancreatic cancer. We recently discovered PRSS3 to be over-expressed in metastatic human pancreatic cancer cells. This study aimed to elucidate the role of PRSS3 in the growth and metastasis of human pancreatic cancer. <h3>Methods</h3> PRSS3 expression in human pancreatic cancer cell lines was detected by qPCR and immunoblotting. The effect of PRSS3 on cancer cell proliferation, migration and invasion in vitro, tumour growth and metastasis in vivo were investigated by manipulation of PRSS3 expression in human pancreatic cancer cell lines. VEGF expression was detected by ELISA, and the pathway through which PRSS3 regulates VEGF expression was investigated. The therapeutic effect of targeting this pathway on metastasis was assessed in vivo. Immunohistochemistry was employed to detect PRSS3 expression in human pancreatic cancer tissues. <h3>Results</h3> PRSS3 was over-expressed in the metastatic PaTu8988s cell line, but not in the non-metastatic PaTu8988t cell line. Over-expression of PRSS3 promoted pancreatic cancer cell proliferation as well as invasion in vitro, and tumour progression and metastasis in vivo. Stepwise investigations demonstrated that PRSS3 upregulates VEGF expression via the PAR1-mediated ERK pathway. ERK inhibitor significantly delayed the progression of metastases of pancreatic cancer and prolonged the survival of animals bearing metastatic pancreatic cancer (p&lt;0.05). 40.54% of human pancreatic cancers (n=74) were positive for PRSS3 protein. A significant correlation was observed between PRSS3 expression and metastasis (p&lt;0.01). Multivariate Cox regression analysis indicated that patients with PRSS3 expression in their tumours had a shorter survival time compared to those without PRSS3 expression (p&lt;0.05). <h3>Conclusion</h3> PRSS3 plays an important role in the progression, metastasis and prognosis of human pancreatic cancer. Targeting the PRSS3 signalling pathway may be an effective and feasible approach for treatment of this lethal cancer.
Treatment of Corticosteroid-Responsive Autoimmune Inner Ear Disease With Methotrexate
Authors: Jeffrey P. Harris, Michael H. Weisman, Jennifer M. Derebery, Mark A. Espeland, Bruce J. Gantz, A. Julianna Gulya, Paul E. Hammerschlag, Maureen Hannley, Gordon B. Hughes, Richard Moscicki, Ralph A. Nelson, John K. Niparko, Steven D. Rauch, Steven A. Telian, Patrick E. Brookhouser
Journal: JAMA (2003)

A number of therapies have been proposed for the long-term management of corticosteroid-responsive, rapidly progressive, bilateral sensorineural hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged as the benchmark agent but has not been rigorously evaluated for hearing improvement in patients with AIED.To assess the efficacy of long-term methotrexate in maintaining hearing improvements achieved with glucocorticoid (prednisone) therapy in patients with AIED.A randomized, double-blind, placebo-controlled trial conducted from February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive, bilateral sensorineural hearing loss at 10 tertiary care centers in the United States.Randomization to either oral methotrexate (15 to 20 mg/wk; n = 33) or placebo (n = 34), in combination with an 18-week prednisone taper. Follow-up examinations, including audiometric evaluation, were performed at 4, 8, 12, 24, 36, 48, and 52 weeks, or until hearing loss was documented.Maintenance of hearing improvement achieved from prednisone treatment.Sixty-seven patients (57.8%) enrolled in the prednisone challenge experienced hearing improvement. Twenty-five patients (37%) experienced hearing improvements in both ears. Of the individuals who reached study end points, 24 (80%) of 30 end points were because of measured hearing loss in the methotrexate group and 29 (93.5%) of 31 end points were because of measured hearing loss in the placebo group (P =.15). Methotrexate was no more effective than placebo in maintaining the hearing improvement achieved with prednisone treatment (hazard ratio, 1.31; 95% confidence interval, 0.79-2.17; P =.30).Methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED.
A Randomized Phase II Trial of the Matrix Metalloproteinase Inhibitor BMS-275291 in Hormone-Refractory Prostate Cancer Patients with Bone Metastases
Authors: Primo N. Lara, Walter M. Stadler, Jeff Longmate, David I. Quinn, Jason Wexler, Marta Van Loan, Przemyslaw Twardowski, Paul H. Gumerlock, Nicholas J. Vogelzang, Everett E. Vokes, Heinz Josef Lenz, James H. Doroshow, David R. Gandara
Journal: Clinical Cancer Research (2006)

Abstract Background: BMS-275291 is a selective matrix metalloproteinase inhibitor (MMPI) that does not inhibit sheddases implicated in the dose-limiting arthritis of older MMPIs. We conducted a randomized phase II trial of two doses of BMS-275291 (1,200 versus 2,400 mg) in hormone-refractory prostate cancer (HRPC) patients with bone metastases to probe for a dose-response relationship and to assess differential toxicities. Serial serum and urine specimens were collected to assess for markers of bone metabolism. Methods: The primary end point was 4-month progression-free survival (PFS). Eligibility criteria included documentation of androgen-independent disease (including anti-androgen withdrawal), skeletal metastasis, adequate end-organ function and performance status, and no more than one prior chemotherapy regimen. Patients were randomized to 1,200 mg orally once daily (arm A) or 1,200 mg orally twice daily (arm B). Response was assessed every 56 days. Results: Eighty patients were enrolled: 39 in arm A and 41 in arm B. There were no responders by prostate-specific antigen or measurable disease to treatment. Stable disease was noted at 8 weeks in 39% of patients in arm A and in 17% of patients in arm B. Progression of disease at 8 weeks was seen in 61% of patients in arm A versus 83% of patients in arm B. Median survival time was 21.6 months (95% confidence interval, 17.5; not reached), whereas median PFS time was 1.8 months (95% confidence interval 1.74; 2) for all patients. Patients in arm A had a median survival time that was not reached, whereas patients on arm B has a median survival time of 21 months (P = 0.2). PFS at 4 months favored arm A: 22% versus 10% (log-rank, P = 0.008). Grade 3 toxicities occurred in 5 (13%) patients in arm A and in 9 (22%) patients in arm B. Grade 4 toxicities were uncommon (only 4% of patients): one each of thrombosis, fatigue, and motor neuropathy was seen in the arm B. Bone marker studies showed that baseline serum levels of N-telopeptide, osteocalcin, procollagen I NH2-terminal propeptide, and PICP had prognostic significance for PFS and/or overall survival. Conclusions: Regardless of dose schedule, BMS-275291 was well tolerated in HRPC patients and had no dose-limiting arthritis. Toxicities differed modestly according to the dose schedule employed. As overall survival and PFS favored the once daily schedule, this dose schedule is recommended for future studies. Baseline markers of bone metabolism may have prognostic value in HRPC patients with bone metastases.
The E3 ubiquitin ligases β-TrCP and FBXW7 cooperatively mediates GSK3-dependent Mcl-1 degradation induced by the Akt inhibitor API-1, resulting in apoptosis
Authors: Hui Ren, Junghui Koo, Baoxiang Guan, Ping Yue, Xingming Deng, Mingwei Chen, Fadlo R Khuri, Shi-Yong Sun
Journal: Molecular Cancer (2013)

Abstract Background The novel Akt inhibitor, API-1, induces apoptosis through undefined mechanisms. The current study focuses on revealing the mechanisms by which API-1 induces apoptosis. Results API-1 rapidly and potently reduced the levels of Mcl-1 primarily in API-1-senstive lung cancer cell lines. Ectopic expression of Mcl-1 protected cells from induction of apoptosis by API-1. API-1 treatment decreased the half-life of Mcl-1, whereas inhibition of the proteasome with MG132 rescued Mcl-1 reduction induced by API-1. API-1 decreased Mcl-1 levels accompanied with a rapid increase in Mcl-1 phosphorylation (S159/T163). Moreover, inhibition of GSK3 inhibited Mcl-1 phosphorylation and reduction induced by API-1 and antagonized the effect of API-1 on induction of apoptosis. Knockdown of either FBXW7 or β-TrCP alone, both of which are E3 ubiquitin ligases involved in Mcl-1 degradation, only partially rescued Mcl-1 reduction induced by API-1. However, double knockdown of both E3 ubiquitin ligases enhanced the rescue of API-1-induced Mcl-1 reduction. Conclusions API-1 induces GSK3-dependent, β-TrCP- and FBXW7-mediated Mcl-1 degradation, resulting in induction of apoptosis.
Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.
Authors: D R Smith, P J Polverini, S L Kunkel, M B Orringer, R I Whyte, M D Burdick, C A Wilke, R M Strieter
Journal: The Journal of Experimental Medicine (1994)

We investigated the role of interleukin 8 (IL-8) in mediating angiogenesis in human bronchogenic carcinoma. Increased quantities of IL-8 were detected in tumor tissue as compared with normal lung tissue. Immunohistochemical staining of tumors revealed primary localization of IL-8 to individual tumor cells and demonstrated the capacity of tumor to elaborate IL-8. Functional studies that used tissue homogenates of tumors demonstrated the induction of both in vitro endothelial cell chemotaxis and in vivo corneal neovascularization. It is important to note that the addition of neutralizing antisera to IL-8 to these assays resulted in the marked and specific attenuation of these responses. Our observations definitively establish IL-8 as a primary mediator of angiogenesis in bronchogenic carcinoma and offer a potential target for immunotherapies against solid malignancies.
Dipyridamole-induced capillary endothelial cell proliferation in the rat heart--a morphometric investigation
Authors: T. MATTFELDT, G. MALL
Journal: Cardiovascular Research (1983)

20 male Wistar rats were randomly divided into two equal groups. Each experimental rat was injected with 4 mg . kg-1 dipyridamole ip twice daily for 4 weeks, the control rats received sham injections of an equal volume of saline. The rats were fixed by retrograde vascular perfusion. Left ventricular papillary muscles were sampled for light and electron microscopic morphometry. By means of a combination of serial section reconstruction and morphometry we could demonstrate that the number of capillary endothelial cell nuclei per tissue volume had increased by 37% (P less than 0.01), whereas the average nuclear volume remained constant. All other morphometric parameters (volume densities of myocardial cells, capillaries, cellular and non-cellular interstitial tissue, and myocardial cell nuclei; surface area, diameter, and density of capillaries; volume densities of myofibrils, mitochondria, and sarcoplasmic matrix; surface areas of the inner and outer mitochondrial membranes; dimensions of average mitochondrial section profiles) were unchanged. We conclude that chronic dipyridamole application induces proliferation of capillary endothelial cells in the rat myocardium, possibly by an increase of myocardial blood flow.
Androgen receptor analysis on needle biopsy of the liver: A step closer in determining whether hepatocellular carcinomas are sex hormone-sensitive
Authors: Seymour Mishkin, Shaindel Y. Mishkin, Julius Erdstein
Journal: Hepatology (1989)

The liver is a steroid-responsive organ and contains high levels of androgen receptors (AR). The present study investigated cytosolic AR concentrations in diseased human liver obtained by needle biopsy. Insufficient tissue was available for full Scatchard analysis. Previous studies have shown the binding affinity of the liver AR to be sufficiently constant to allow the use of a single saturating dose analysis, using 3 H-mibolerone as the active ligand, for the estimation of binding sites. Thirteen samples were studied and compared to normal liver. AR was identified in all samples and the level negatively correlated to the degree of liver damage. A role for AR in hepatocellular carcinoma has been postulated and anti-androgens used in treatment. This study shows AR can be measured in needle-biopsy specimens and, if hepatocellular carcinoma is proven to be hormone sensitive, then this technique may help in the assessment of such tumours.
Heparin neutralization by platelet-rich thrombi. Role of platelet factor 4.
Authors: D T Eitzman, L Chi, L Saggin, R S Schwartz, B R Lucchesi, W P Fay
Journal: Circulation (1994)

BACKGROUND Platelets contain several factors that inhibit heparin. This study was designed to assess the heparin-neutralizing activity present in acute, platelet-rich arterial thrombi formed at sites of arterial injury in animals. METHODS AND RESULTS Platelet-rich thrombi (n = 3) were induced in pig coronary arteries by balloon catheter-mediated arterial injury. Soluble extracts were prepared from each thrombus and assayed for the capacity to inhibit heparin in an in vitro clotting assay (activated partial thromboplastin time). Mean heparin-neutralizing activity was 28 U of heparin neutralized per milliliter of thrombus, indicating that 1 vol of coronary thrombus completely inhibited the heparin present in 140 vols of therapeutically anticoagulated (0.2 U heparin/mL) plasma. In contrast, thrombus extracts had no effect on the anticoagulant activity of hirudin, a direct-acting thrombin inhibitor. The heparin-neutralizing activity present in coronary thrombi bound to heparin-agarose and was eluted from it by 1.4 mol/L NaCl, suggesting that platelet factor 4 mediated the antiheparin effect of thrombi. Consistent with this hypothesis, a murine monoclonal antibody to rabbit platelet factor 4 nearly completely inhibited the heparin-neutralizing activity present in rabbit thrombi (n = 3) generated by carotid artery injury. CONCLUSIONS Extracts prepared from platelet-rich arterial thrombi significantly inhibit the in vitro anticoagulant potency of heparin but not of hirudin. This antiheparin effect appears to be mediated by platelet factor 4. These results are consistent with the hypothesis that localized inhibition of heparin at sites of platelet activation may reduce its antithrombotic efficacy. In addition, they suggest an additional mechanism for the apparent superiority of hirudin over heparin as a thrombin inhibitor at sites of arterial injury.
Treatment for multiple myeloma shows promise
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Patients with multiple myeloma who were treated with high dose chemotherapy followed by stem cell rescue lived almost a year longer than patients who had standard treatment, a new study has found.

In the randomised controlled trial, 44% of patients in the intensive treatment group had a complete response to treatment, compared with only 8% in the standard treatment group ( New England Journal of Medicine 2003;348:1875-83).

The study included 401 patients from 83 centres in the United Kingdom and New Zealand and took place between 1993 and 2000. Patients were previously untreated and were aged under 65 years.

Standard treatment (200 patients) was doxorubicin, carmustine, cyclophosphamide, and melphalan every six weeks until maximal response was attained. The number of cycles needed ranged …