tbuckley/cabot-search huggingface dataset:
Profiling of receptor tyrosine kinases (RTK) activation in circulating tumor cells (CTCs) in metastatic tumors using proximity mediated microarray immunoassay
Authors: X. Liu, P. Kim, L. Liu, T. Lee, R. Barham, F. Lin, J. Harvey, B. Ybarrondo, S. Singh
Journal: Journal of Clinical Oncology (2009)

11024 Background: The abnormal activation of HER1 and HER2 has been linked to various types of cancer progression, and the changes in their expression status between primary tumor and CTCs have been reported to occur at a significant frequency. Methods for detecting HER1/HER2 phosphorylation in serially collected CTCs may provide valuable insight into the overall disease profile shift, and therefore lead to better selection of therapy combination for individual patient. Methods: A triple-antibody-enzyme-channeling multiplexed protein microarray platform has been developed to detect the phosphorylation on target molecules. It utilizes a unique immuno-complex formation via co-localization of two detector enzyme-conjugated-antibodies once target proteins are captured on the microarray-surface. The channeling events between two detector enzymes in proximity enabled profiling of the RTKs with a single-cell level sensitivity. The simultaneous binding of three different types of target specific antibodies for signal amplification results in extremely high assay specificity. In order to validate the method on clinical samples, CTCs from 75 cancer patients (stage 3/4) on various therapy regimens were analyzed. Results: We identified 6 patients (8%) with activated HER1, 6 patients (8%) with activated HER2 and 14 (18.5%) patients with dual RTK activation in their CTCs from various types of metastatic cancer. 25 samples from normal subjects showed no detectable HER1/HER2 activation. We also observed discrepancies between HER2 activation status in CTCs and their corresponding primary HER2-IHC status among breast cancer patients. CTCs with activated-HER2 were found in 6 out of 16 (38%) patients with HER2-negative primary breast cancer. In addition, 2 out of 5 HER2-positive breast cancer patients had CTCs with no apparent HER2-activation. Conclusions: The multiplexed-proximity mediated immunoassay successfully detected the activation of RTKs in CTCs isolated from various cancer patients. As CTCs found in metastatic stage represent the most aggressive invading cell population, serial CTC-profiling can lead to better therapy selection/adjustment and disease/treatment monitoring as there are available options to choose appropriate kinase inhibitors for RTK-targeted therapies. [Table: see text]
Identification of an Adverse Biologic Profile in Cyclophosphamide/Metotrexate/5-Fluorouracil Treated Early Stage Breast Cancer Patients by Immunohistochemical Analysis of PI3K/p-Akt Pathway Alterations.
Authors: M. Mottolese, F. Novelli, A. Di Benedetto, E. Melucci, I. Sperduti, L. Perracchio, S. Buglioni, P. Vici, C. Nisticò, P. Pinnarò, A. Fabi, E. Bria
Journal: Cancer Research (2009)

Abstract Background: Akt activation through PI3K, leads to the phosphorylation of p27 protein thus avoiding nuclear entry and inducing mislocation to the cytoplasm of the protein with consequent inhibition of p27 cell cycle inhibitory function. The prognostic role of PI3K/Akt pathway alterations correlating phenotypic profiles with bio-pathologic variables of known clinical importance have been investigated in a retrospective series of early stage breast cancer patients (BC pts) treated with cyclophosphamide/metotrexate/5-fluorouracil based chemotherapy (CMF).Materials and methods: p-Akt, PI3K and p27 expression were evaluated by immunohistochemistry in a series of stage I/II BC pts who underwent conservative surgery and were candidates to receive CMF adjuvant therapy plus radiotherapy. Multiple Correspondence Analysis (MCA) was used to identify sub-groups of pts with different prognosis, while uni- and multivariate Cox regression analyses were applied to determine the impact of parameters identified by MCA on 10-yrs Disease Free Survival (DFS), together with clinico-pathological features. Receiver Operative Curve (ROC) analysis was adopted for optimal cut-off values.Results: In a series of 133 pts, with a median follow-up of 107 months (range 40 to 141), those pts characterized by high Ki67 index, p53+, p-Akt+, PI3K+ and HER2+ (Adverse Biologic Factors, ABF) were associated with tumor relapse at the MCA analysis. ROC analysis dicotomized between pts with a Favourable Biological Profile (FBP, &amp;lt;3 ABF) and Unfavorable Biologic Profile (UBP ≥ 3 ABF). UBP pts showed a significantly shorter 10- yrs DFS than FBP pts at Kaplan-Meier analysis (67.0% vs 91.3%, p=0.0006). According to the multivariate analysis, the biologic profile was the only significant prognostic indicator for longer DFS (p=0.002). Significant factors at uni- and multivariate analysis are shown in the table.Significant factors at uni- and multivariate analysisFactorsUnivariate (HR, 95% CI)p-valueMultivariate (HR, 95% CI)p-valueGrading3.32 (1.31-8.43)0.012--PgR2.37 (1.03-5.48)0.043--UBP4.24 (1.73-10.40)0.0024.24 (1.73-10.40)0.002 Discussion: These data suggest that the activation of Akt may contribute together with high Ki67 index, p53+, p-Akt+, PI3K+ and HER2+ in predicting recurrence in early stage BC pts homogeneously treated with CMF based therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6036.
TAVR AGE PARADOX: THE OLDEST PATIENTS HAVE BETTER THAN EXPECTED OUTCOMES IN THE PARTNER STUDY
Authors: Creighton W. Don, Adam Johnson, Chris Burke, Ashley Lowry, Jeevanantham Rajeswaran, Vinod Thourani, Martin Leon, Edward Verrier, Susheel Kodali, Raj Makkar, Howard Herrmann, Samir Kapadia, Augusto Pichard, Larry Dean, James McCabe, Gabriel Aldea, Mark Reisman
Journal: Journal of the American College of Cardiology (2016)
Edwin Ernest Frederick Keal
Authors: M. Turner-Warwick, R. Keal
Journal: BMJ (2012)

Edwin Ernest Frederick Keal, always affectionately known to his professional colleagues as “Eddie,” was born and brought up in Hull. He left grammar school at 15 to become a shipping clerk, and at the age of 17, in May 1939, he enrolled in the Hull division of the Royal Navy Volunteer Reserve. The RNVR had its own training ship, an anti-aircraft cruiser called HMS Curacao . He was called up in September 1939, when just 18 years old, and took part in the 1940 Norway campaign and the evacuation from Dunkirk. He was quickly selected for officer training, but, because he was only 19 years old, he became a midshipman on the battleship HMS Malaya . In August 1941 he was promoted to sub-lieutenant on the destroyer HMS Gurkha . Posted to the Mediterranean, the ship took part in the Malta convoys. He was seriously wounded on 17 January 1942, when his ship was torpedoed and sunk by a German U-boat. This resulted in an above knee amputation of his left leg at just 20 years of age. After rehabilitation in South Africa he was declared fit for service ashore and sent to a naval air arm training centre in Lancashire, where he met Connie, who was in the …
Heparin Use as a Risk Factor for Intraventricular Hemorrhage in Low-Birth-Weight Infants
Authors: Samuel M. Lesko, Allen A. Mitchell, Michael F. Epstein, Carol Louik, George P. Giacoia, Samuel Shapiro
Journal: New England Journal of Medicine (1986)

In a systematic review of data on drug use and adverse clinical events in infants with birth weights under 2000 g, we observed an association between germinal matrix-intraventricular hemorrhage and the use of heparin to maintain the patency of vascular catheters. Sixty-six infants with germinal-matrix (periventricular) or intraventricular hemorrhage or both (cases) were matched with 254 infants with other conditions (controls), and analysis, taking the matching factors into account, yielded an odds ratio of 14.0 (95 percent confidence interval, 5.4 to 34). When potential confounding factors were taken into account, the odds ratio was 3.9 (1.4 to 11). The association did not appear to vary according to the severity of hemorrhage or to the method of administration or dose of heparin. The data suggest that the routine use of heparin in neonatal intensive care units is associated with a fourfold increase in the risk of germinal matrix-intraventricular hemorrhage. Because of the possibility that confounding may have been incompletely controlled for, the true risk cannot be determined from these data, and a controlled clinical trial of heparin use in low-birth-weight infants is recommended. (N Engl J Med 1986; 314: 1156–60.)
Rosacea is linked to Parkinson’s disease in Danish study
Authors: Jacqui Wise
Journal: BMJ (2016)

A significantly increased risk of Parkinson’s disease in patients with rosacea has been reported in a Danish study published in JAMA Neurology , but the authors say that further research is needed to confirm this observation.1

The cause of rosacea, a common chronic inflammatory condition of the skin, is unclear. However, increased activity of the enzyme matrix metalloproteinase seems to play an important role. Matrix metalloproteinases have also been implicated …
New Approaches to Cancer Chemoprevention With Difluoromethylornithine and Selenite
Authors: C. Ip, H. J. Thompson
Journal: JNCI Journal of the National Cancer Institute (1989)

New approaches to enhancing D,L-α-difluoromethylornithine (DFMO) inhibition of DMBA-induced mammary tumorigenesis were investigated. It is reasoned that perturbation of a second regulatory element in polyamine biosynthesis, i.e., the generation of propylamine groups from S-adenosylmethionine (AdoMet), would potentiate the effectiveness of DFMO. Precursor availability for AdoMet was limited when rats were fed a low methionine diet. The diet of control rats was supplemented with 0.3% methionine. DFMO, when added to the diet at 0.1%, suppressed tumorigenesis, regardless of methionine levels, although its efficacy was significantly enhanced by the low methionine diet Selenite, another effective chemopreventive agent in this tumor model, also requires AdoMet for its metabolism. However, the anticarcinogenic action of selenite is not compromised by low dietary methionine. The differential sensitivity of DFMO and selenium chemoprevention to low dietary methionine, therefore, provides an opportunity to test for an additive effect. Results of the combination regimen study showed that the incidence and yield of DMBA-induced mammary tumors were significantly lower in the two-agent protocol compared to either DFMO or selenite alone. The mechanism(s) that accounts for the heightened efficacy of combined DFMO and selenite chemoprevention will be discussed. [J Natl Cancer Inst 81:839–843, 1989]
Outcomes of endoscopic papillectomy in elderly patients with ampullary adenoma or early carcinoma
Authors: N. Nguyen, J. Shah, K. Binmoeller
Journal: Endoscopy (2010)

Outcomes for 14 elderly (age ≥ 70 years) patients (79.4 ± 1.0 years) who underwent endoscopic papillectomy for ampullary tumors were compared with those of 22 younger (age < 70 years) patients (52.5 ± 1.9 years). There were no differences in procedural success (100 %), bleeding (5/14 vs. 6/22), adenoma recurrence (0/14 vs. 2/22) and median survival (24.0 vs. 25.5 months) between the elderly and younger patients. In younger patients, although adenoma recurrences (n = 2) were managed endoscopically, invasive adenocarcinomas (n = 3) were treated by pancreatoduodenectomy. All elderly patients with invasive (T2) tumors (n = 5) were not surgically fit and underwent successful palliation with further endoscopic resection and stenting. Whilst all younger patients survived, five elderly patients died but three of these deaths were not cancer-related. Advanced age, therefore, did not adversely influence the outcomes of endoscopic papillectomy, suggesting it may be a treatment of choice for elderly patients with ampullary tumors or early cancer who are deemed unfit for surgery.
Lobar Extent of Pulmonary Lymphangitic Carcinomatosis
Authors: NAOKO KASHITANI, RYOSUKE EDA, TOYOHISA MASAYOSHI, HIROYASU TAKEYAMA, SHIGEKI MAKIHARA, YASUHIRO KITAMURA, YOSHIKI YAMAMOTO, YOSHIO HIRAKI
Journal: Clinical Nuclear Medicine (1996)

Two cases of histologically proven lobar pulmonary lymphangitic carcinomatosis are reported in which well-defined sites of accumulation of Tl-201 and Tc-99m MIBI were observed. The combination of Tl-201 and Tc-99m MIBI SPECT can detect the extent of pulmonary lymphangitic carcinomatosis.
Soft Tissue Metastases and Lung Cancer Recurrence Detected by Tc-99m Depreotide Scintigraphy
Authors: JOHN S. MILIZIANO, YONG C. BRADLEY
Journal: Clinical Nuclear Medicine (2002)

A 63-year-old woman with previously treated stage I lung cancer was reexamined 5 years later for recurrence. A conventional work-up using computed tomographic scanning and transbronchial biopsy showed nothing abnormal. A Tc-99m depreotide scan, however, led to a noninvasive diagnosis of lung cancer recurrence with metastases, and it directed a noninvasive tissue diagnosis.
P312 UNTARGETED H-NMR SPECTROSCOPY DEMONSTRATES A UNIQUE METABOLIC PHENOTYPE OF ALCOHOLIC HEPATITIS
Authors: S. Atkinson, A. Wijeyesekera, M.J. McPhail, N. Vergis, D.L. Shawcross, J. Mellor, E. Holmes, M.R. Thursz
Journal: Journal of Hepatology (2014)
False-positive Cholecystoduodenal Fistula on a Hepatobiliary Study After Liver Transplantation
Authors: RONALD J. ROSENBERG, RATHNAKARA M. SHERIGAR, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1999)

A 36-year-old woman received a liver transplant. One week after surgery, hepatobiliary imaging was performed. The liver was functioning poorly, as evidenced by slow accumulation of the radiotracer. Four hours after injection, a lower hepatic pole accumulation of activity resembled the gallbladder, with drainage into the duodenum (a cholecystoduodenal fistula). However, the gallbladder had not been transplanted. That the collection was due to pooling in the dilated colon was shown by a contrast CT study.
Abstract 4232: GFP imaging of DNA repair after UV irradiation of cancer cells
Authors: Yasunori Tome, Shuya Yano, Hiroki Maehara, Elena V. Efimova, Fuminori Kanaya, Hiroyuki Tsuchiya, Katsuro Tomita, Michael Bouvet, Robert M. Hoffman
Journal: Cancer Research (2012)

Abstract The ability to image DNA repair in cancer cells after irradiation as well as its inhibition by potential therapeutic agents is important for the further development of radiotherapy of cancer. The relocalization of GFP fused to the chromatin-binding domain of a check-point-adapter protein 53BP1 was imaged after UV irradiation of breast cancer and MiaPaca-2 human pancreatic cancer cells. 53BP1 is a DNA repair protein that is over-expressed when double-stranded breaks occur in DNA. During live-cell imaging, 53BP1-GFP foci formation was observed within 15 minutes after UV irradiation. Most 53BP1 foci resolved by 90 min. To block UV-induced double stranded break (DSB) repair in cancer cells, we targeted poly (ADP-ribose) polymerase (PARP) with ABT-888 (veliparib). PAPR inhibition markedly enhanced UV-irradiation-induced foci persistence, even more than 90 min after UV irradiation, and decreased cell proliferation of breast and pancreatic cancer cells. The results suggest UV-irradiation and PAPR inhibition are a promising therapeutic combination for breast and pancreatic 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 4232. doi:1538-7445.AM2012-4232
AB0709 Association of tinu, nodal tuberculosis and renal amylosis
Authors: L. Baili, Z. Aydi, M. Dridi, B. Ben Dhaou, S. Kochbati, F. Boussema, L. Rokbani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tubulo-interstitial nephritis may be caused by drugs, infections or systemic diseases. However, the precise cause and etiology of the disease are unclear. Uveitis is a general terme of the inflammation of the iris and choroid. This ocular disorder is known to be complicated with several systemic disorders such as sarcoîdosis, Behecet's disease and toxoplasmosis. The association of tubulo-interstitial nephritis and uveitis (TINU) was first described in 1974. Subsequently, Dobrin et al reported two cases of interstitial nephritis complicated with anterior uveitis. Since then, this association has become known as Dubbin's syndrome. <h3>Objectives</h3> We present a case of TINU associated with nodal tuberculosis and renal amylosis. <h3>Results</h3> A 68-year-old woman with 4 months history of nodal tuberculosis diagnosed on histological study of cervical nodal biopsy was referred to our department for painful red eye and decreased vision in both eyes. Physical examination was unremarkable except for the bilateral red eye. Ophtalmological examination objective revealed bilateral non-granulomatous anterior uveitis. Laboratory finding was normal except for proteinuria (1g/24h). <i>Urinary cytobacteriological</i>exam showed <i>aseptic leukocyturia</i>. Antinuclear and antineutrophil cytoplasmic antibody test results were negative. Serological tests of infectious were negative. An ophthalmological examination revealed bilateral non-granulomatous anterior uveitis. Abdominal ultrasonography was normal. Histopathological examination of kidney biopsy showed <i>amyloid deposits</i> and tubulo-intersitial nephritis. Diagnosis of TINU was made. The patient was treated with antitubercular drugs. Eight months later, 24h urinary protein gets better and uveitis improved. <h3>Conclusions</h3> TINU syndrome no longer appears to be so rare, but its mechanism remains unclear. It should be considered as differential diagnosis of unexplained tubule-interstitial nephritis especially in the presence of ocular finding. <h3>Disclosure of Interest</h3> None Declared
Abstract 891: The association of single nucleotide polymorphisms in folate metabolism genes with hypermethylation patterns in smokers at high risk for lung cancer
Authors: Kristina G. Flores, Christine A. Stidley, Maria A. Picchi, Amanda J. Mackey, Tim Byers, Marianne Berwick, Steven A. Belinsky, Shuguang Leng
Journal: Cancer Research (2011)

Abstract Hypermethylation of promoter regions serve as potential biomarkers for the early detection of lung cancer. Because folate metabolism is necessary for nucleotide synthesis and DNA methylation reactions, that when perturbed, may both contribute to the development of cancer, hypermethylation of promoter regions in folate metabolism genes may be particularly important to explore. Dietary folate was recently found to protect against gene promoter hypermethylation patterns. This study investigated the association of functional and haplotype tagging single nucleotide polymorphisms (SNPs) in folate metabolism genes with promoter hypermethylation in sputum cell DNA from a cohort of current and former smokers (n=937). This cohort was a subset of the Lovelace Smokers’ Cohort of approximately 2000 high risk current and former smokers who were non-Hispanic white and for whom a complete methylation panel was obtained. Methylation panel status from a 12 gene panel was dichotomized into high and low methylation based on a cutoff of the number of genes methylated (&amp;gt; = 3 genes for women and &amp;gt; = 4 genes for men were categorized as high). Lymphocyte DNA was interrogated on a 96 SNP Illumina Goldengate platform. A SNP in the cystathionine-beta synthase gene (CBS), that converts homocysteine to cystathionine, was found to be significantly associated with gene promoter hypermethylation. Analyses used logistic regression and adjusted for multiple comparisons. There was an interaction between gender and CBS (p&amp;lt;0.0001), so we conducted a stratified analysis by gender. Males with the variant allele had an increased risk of methylation (OR = 3.61; 95% CI: 1.71, 7.64); p&amp;lt;0.001) and females with the variant allele had a decreased risk for methylation (OR = 0.64; 95% CI: 0.40, 1.00; p=0.05). A 20% reduction in CBS gene transcription was seen in bronchial epithelial cells heterozygous for the CBS variant allele compared to cells without the variant allele but was not statistically significant. Epidemiological studies have shown that men have higher levels of homocysteine compared to women but the mechanisms regulating this difference are not known. This study shows that a SNP in the CBS gene is associated with methylation patterns in smokers at high risk to develop lung cancer and differs by gender. This work may further help to elucidate the differences in lung cancer risk by gender. Grant Support: This work is supported by K01CA128823 NCI and R01CA097356 NCI Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 891. doi:10.1158/1538-7445.AM2011-891
Tuberculous abscess formation with liver invasion after endoscopic ultrasound-guided fine-needle aspiration for abdominal lymphadenopathy
Authors: Shogo Kumagai, Yu Muta, Shujiro Yazumi
Journal: Endoscopy (2014)

A 62-year-old woman was referred to our hospital because of low-grade fever, with a suspected diagnosis of extrapulmonary tuberculosis. Computed tomography (CT) revealed lymphadenopathy, 25 mm in diameter, around the common hepatic artery ([Fig. 1]). Endoscopic ultrasonography (EUS) revealed hypoechoic lesions measuring about 20 mm ([Fig. 2]). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed and indicated no sign of malignancy. Polymerase chain reaction and culture of the biopsied specimens were negative for Mycobacterium tuberculosis.
Malignant Smooth-Muscle Tumors (Leiomyosarcomas) of Soft-Tissue Origin
Authors: John T. Phelan, William Sherer, Perez Mesa
Journal: New England Journal of Medicine (1962)

MALIGNANT smooth-muscle tumors (leiomyosarcomas) of soft-tissue origin are rare tumors, as indicated by the fact that in a review of the recent surgical literature, only one series, comprising 36 cases, has been documented.1 Because of the relative infrequency of this type of tumor the present report, which includes an additional 10 cases, provides further information concerning the clinicopathological features of these tumors.MaterialDuring the five years 1955 to 1960, 10 cases of leiomyosarcoma of soft-tissue origin were treated at Roswell Park Memorial Institute, Buffalo, New York. Histologic tissue from each patient was available for study, and the diagnosis of . . .