tbuckley/cabot-search huggingface dataset:
Vascular Endothelial Growth Factor Trap Combined with Paclitaxel Strikingly Inhibits Tumor and Ascites, Prolonging Survival in a Human Ovarian Cancer Model
Authors: Limin Hu, Judith Hofmann, Jocelyn Holash, George D. Yancopoulos, Anil K. Sood, Robert B. Jaffe
Journal: Clinical Cancer Research (2005)

Abstract Ovarian cancer is characterized by i.p. carcinomatosis and massive ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis and vascular leakage leading to ascites. We assessed the efficacy of a soluble decoy receptor (VEGF Trap) combined with paclitaxel, in a mouse model of human ovarian cancer. Tumor burden after VEGF Trap plus paclitaxel was reduced by ∼98% versus controls. No measurable ascites developed in the treated group. Morphologic studies showed that most residual tumor had degenerative changes. Diaphragmatic and hepatic tumors were not found in the VEGF Trap plus paclitaxel group in contrast to controls, indicating lack of metastasis. In vivo FITC-lectin tumor vessel imaging showed sparse, short, straight vessels in treated mice as compared to controls, in which vessels were numerous, irregular, tortuous, and leaky. In a survival study, all controls underwent euthanasia between 29 and 58 days after tumor cell inoculation (cachexia, extensive ascites, and tumor masses). In the VEGF Trap plus paclitaxel group, mice were ambulating and eating normally with no signs of disease for at least 81 days after tumor cell inoculation, and survival occurred for 129.9 ± 38.88 days with no further treatment. We conclude that combination therapy with VEGF Trap plus paclitaxel may provide a novel, long-lasting therapeutic strategy for treatment of patients with ovarian cancer associated with ascites.
Malignant pleural effusion: would the real cause please stand up?
Authors: RW Light, H Hamm
Journal: European Respiratory Journal (1997)

Pleural effusions in patients with malignant disease are not invariably due to metastatic spread to the pleura and thus, they are not always incurable. For example, about 5% of patients with effusions due to lung cancer have subsequently been found to be operable and curable [1]. It is, therefore, important to assess the potential curability in all cancer patients with cytologically negative effusions, since they may not only be free from pleural metastases but also from tumour spread elsewhere. On the other hand, autopsy studies indicate that only about 55‐60% of patients with proven pleural metastases develop pleural effusions. What are the mechanisms that cause the development of an effusion in one patient with malignant involvement of the pleura and what prevents it in another? In this issue of the Journal, SAHN [2] suggests that neoplastic involvement of the lymphatic drainage system, either in the parietal pleura and/or in the mediastinum, is the primary mechanism by which pleural metastases cause pleural effusions. This leads to accumulation of the fluid which normally leaves the pleural space. These conclusions are based primarily on postmortem studies in which the presence of pleural effusions was correlated with the autopsy findings [3, 4]. If the lymphatic clearance is normal, excess fluid that enters the pleural space can usually be removed, since the maximum capacity of the lymphatics for fluid removal is up to 25 times the normal rate of fluid formation [5]. Therefore, unless the amount of pleural fluid being formed is very high, pleural fluid will accumulate only if there is also decreased lymphatic clearance. Indeed, it has been shown that the clearance of fluid from the pleural space is decreased in patients with malignant pleural effusions [6]. However, there are several observations that seem to be incompatible with the theory that lymphatic obstruction is solely responsible for the pleural fluid accumulation.
R-CHOP14 Compared to R-CHOP21 in Elderly Patients with Diffuse Large B-Cell Lymphoma: Results of the Interim Analysis of the LNH03-6B GELA Study.
Authors: Richard Delarue, Herve Tilly, Gilles Salles, Christian Gisselbrecht, Nicolas Mounier, Marion Fournier, Thierry Jo Molina, Caroline Bonmati, Hervé Ghesquieres, Michel Blanc, Delphine Germain, Laurence Girard, Corinne Haioun, Andre Bosly
Journal: Blood (2009)
A prospective evaluation of magnetic resonance cholangiopancreatography in patients with suspected bile duct obstruction
Authors: H E Adamek, J Albert, M Weitz, H Breer, D Schilling, J F Riemann
Journal: Gut (1998)

The value of magnetic resonance cholangiopancreatography (MRCP) is under debate.To assess the diagnostic accuracy of MRCP and endoscopic retrograde cholangiopancreatography (ERCP) and to determine whether MRCP may help to prevent unnecessary interventional procedures.Eighty six patients with suspected common bile duct obstruction who presented between January and December 1996 were enrolled. Twenty six were excluded due to anatomical reasons or because MRCP or ERCP could not be performed successfully. Results of MRCP were interpreted by two radiologists and a gastroenterologist unaware of clinical diagnosis. Final diagnosis was determined by ERCP and histopathological findings or a follow up of at least 12 months.MRCP images of diagnostic quality were obtained in all 60 patients. Thirteen patients had a clear bile duct. Sensitivity and specificity for the detection of any abnormality (n=47) were 89% and 92%, and for the detection of malignancy (n=27) 81% and 100%, respectively. These results were equivalent to the respective figures of ERCP (91% and 92% for any abnormality, and 93% and 94% for malignant diseases).MRCP is as sensitive as ERCP in the evaluation of bilary tract diseases. As the specificity of this non-invasive technique is close to 100%, MRCP may prevent inappropriate invasive explorations of the common bile duct and pancreatic duct.
Persistent Right Jugular Lymph Sac Simulating Cervical Tumor
Authors: ISRAEL S. STEINBERG
Journal: Circulation (1958)

A patient who had had trauma to the right shoulder and upper chest complained of a right supraclavicular mass. Examination revealed a cystic tumor made larger by performance of the Valsalva maneuver. Angiocardiography demonstrated that there was partial stenosis of the terminal end of the right innominate vein. This and the Valsalva maneuver were responsible for the filling of a right persistent jugular lymph sac that simulated a cervical tumor.
The future incidence of cutaneous melanoma within the U.K.
Authors: B.L. Diffey
Journal: British Journal of Dermatology (2004)

Background The incidence of cutaneous malignant melanoma continues to rise in the U.K., where since the 1970s malignant melanoma has seen the largest increase in incidence rates compared with other major cancers. To counteract this rise, sun awareness campaigns have been introduced in this and several other countries since the 1980s with the object of encouraging people to limit their exposure to strong sunshine and to avoid sunburn in the expectation that these interventions will act favourably on skin cancer incidence. Objectives To predict the incidence of cutaneous malignant melanoma in the British population over the next half-century as a consequence of either a stabilization or a reduction in lifetime risk of melanoma for recent and future birth cohorts so that cancer services can be planned appropriately over the coming years. Methods An age-cohort model has been developed that estimates future incidence rates of melanoma in the U.K. Results The results suggest that the benefits of intervention strategies, assuming that these will translate eventually into a downturn in melanoma incidence, may not be seen for another 30 years or so, by which time the predicted age-standardized rate of melanoma may be around twice that presently observed. Conclusions Prevention of deaths from melanoma depends on both reducing incidence and achieving earlier diagnosis. This analysis has indicated that the former is unlikely to be realized in the U.K. for some decades, and so early detection of suspected lesions, with prompt surgery to remove confirmed tumours, is paramount if mortality from melanoma is to be kept in check.
Effects of hyperthermic stress on myocardial function during experimental coronary ischemia.
Authors: A J Liedtke, H C Hughes
Journal: Circulation Research (1976)

We evaluated hyperthermic influences on ischemic hearts by comparing two groups of intact working swine hearts (n = 20) made globally ischemic. Heart muscle temperature was selectively increased from 37.5 +/- 0.3 degrees C to 39.7 +/- 0.3 degrees C in one group (n = 11) by warming the coronary perfusate. Ischemia in normothermic hearts significantly (P less than 0.05) decreased mechanical function (as reflected by increases in left ventricular end-diastolic pressure [LVEDP]), myocardial oxygen consumption (MVO2), glucose uptake, glycolytic flux, free fatty acid (FFA) uptake and oxidation, and tissue stores of high energy phosphates. Hearing in ischemic hearts further depressed mechanical function at similar reductions in coronary flow and MVO2. Glucose uptake was terminally increased over normothermic values (329 vs. 221 mumol/hr per g) as was glycolytic metabolism, FFA uptake (26 vs. 17 mumol/hr per g), and FFA oxidation (21 vs. 11 mumol/hr per g). However, these changes were not translated into increased energy stores of tissue creatine phosphate and ATP. Thus, in ischemic hearts, hyperthermia neither prevented the development of mechanical deterioration nor improved oxidative phosphorylation despite increases in metabolic substrate utilization. These data suggest that in experimental global ischemia heat is an added energy drain in already burdened myocardium.
MIP-2 secreted by epithelial cells increases neutrophil and lymphocyte recruitment in the mouse intestine
Authors: Y Ohtsuka
Journal: Gut (2001)

<h3>BACKGROUND</h3> Invasion of the intestinal mucosa by leucocytes is a characteristic of intestinal inflammation but the role of the epithelium in orchestrating this recruitment has not been examined in vivo. Cultured intestinal epithelial cells secrete a wide variety of chemokines, often in response to agents present in the intestinal lumen. Macrophage inflammatory protein 2 (MIP-2) is a chemokine that attracts neutrophils, and its secretion from intestinal epithelial cells is enhanced by inflammatory stimuli such as interleukin 1β. We hypothesised that the production of MIP-2 by epithelial cells would increase leucocyte migration into the intestine. <h3>AIM</h3> To study the effects of a chemokine secreted from intestinal epithelial cells in vivo. <h3>METHODS</h3> MIP-2 was expressed in the mouse intestinal epithelium using an epithelial cell specific promoter from the gene encoding the intestinal fatty acid binding protein. The intestines of these transgenic mice were then analysed. <h3>RESULTS</h3> Epithelial cells from transgenic mice expressed MIP-2 but wild-type mice did not. Neutrophil recruitment, examined by myeloperoxidase (MPO) staining and total MPO activity per unit weight of intestine, was significantly increased in transgenic mice in both the small intestine and proximal colon, and this was blocked by anti-MIP-2 antibody treatment. Both intraepithelial and lamina propria lymphocytes were also increased in transgenic mice. They showed chemotactic activity to MIP-2 in the Boyden chambers and expressed MIP-2 receptor (CXCR-2) mRNA confirmed by reverse transcription-polymerase chain reaction. <h3>CONCLUSION</h3> These experiments are the first to show a functional role for epithelial chemokines in vivo and reveal an unexpected role for the neutrophil chemokine MIP-2 in controlling mucosal lymphocyte migration.
Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B5b (CYB5B)
Authors: Derek Murphy, Jeremy Parker, Minglong Zhou, Faisal M Fadlelmola, Christian Steidl, Aly Karsan, Randy D Gascoyne, Hong Chen, Diponkar Banerjee
Journal: Molecular Cancer (2010)

Abstract Background We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two independent methods, 2) study the expression of the protein and its encoding mRNA in reactive lymph nodes, normal lymphocytes and CD34+ bone marrow precursor cells, 3) analyse patterns of expression of the protein in tissue microarrays assembled from a large number of diagnostic clinical biopsies from patients with HL, and 4) determine the copy number variation and mutation status of the encoding gene in HL cell lines. Results Peptide sequencing by LC-MS/MS and protein identification by protein array screening identified a single protein, CYB5B. No mutations were detected in the CYB5B gene in HL cell lines. Quantitative PCR showed CYB5B gene expression was increased in HL and NHL cell lines. Array CGH using a submegabase resolution tiling array revealed gains in the CYB5B locus in HL cell lines KMH2 and L428. Membrane expression was seen in Reed-Sternberg cells in clinical biopsies from patients with HL but not in reactive lymph nodes. Bone marrow CD34+ precursor cells were CYB5B negative on the cell surface. RT-PCR assays of RNA extracted from T and B cell enriched fractions obtained from normal peripheral blood mononuclear cells, reactive lymph nodes, tonsils and normal bone marrow samples showed no evidence of increased mRNA levels of CYB5B in comparison to housekeeping gene GAPDH . Conclusions The 21 kDa protein overexpressed in HL and aggressive NHL is identical to CYB5B. CYB5B gene expression is increased in a subset of HL and NHL cell lines tested. This is associated with CYB5B gene amplification in HL cell lines KMH2 and L428. CYB5B may be a potential target for antibody-based therapy of HL and aggressive NHL as although cytoplasmic expression is present in reactive lymphocytes, it is not expressed on the cell surface of non-neoplastic lymphocytes or bone marrow precursor cells.
Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis
Authors: E.Y. Seo, D.H. Lee, Y. Lee, K.H. Cho, H.C. Eun, J.H. Chung
Journal: British Journal of Dermatology (2011)

Background Seborrhoeic keratoses (SKs) are very common benign epidermal lesions without malignant potential. Ultraviolet radiation, old age and viruses are well-known risk factors for disease development. However, the pathomechanisms of SK are not fully understood. Objectives To detect and characterize the genes that are involved in the pathogenesis of SK. Methods We performed a gene expression study using paired lesional and nonlesional skin samples from patients with SK. Results We identified and validated 19 differentially expressed genes in SK. Of these 19 genes, we focused on p63 transcription factor, which plays a pivotal role in epidermal development by regulating its transcriptional programme. We found by immunofluorescence that the expression of ΔNp63α, the most abundantly expressed p63 isoform, was significantly increased in SK as compared with normal skin. Moreover, siRNA-mediated knockdown of ΔNp63 led to the downregulation of 11 genes, including a member of the tensin family TNS4. Chromatin immunoprecipitation assay revealed that TNS4 was a target gene of p63. Conclusions We identified upregulated genes in SK using genome-wide cDNA microarray and elucidated the functional contribution of p63 to the disease transcriptome by gene-silencing assay. Taken together, these data may provide a novel insight into the molecular basis of these benign skin lesions.
Reversal of left ventricular diastolic dysfunction after kidney-pancreas transplantation in type 1 diabetic uremic patients.
Authors: P Fiorina, E La Rocca, E Astorri, G Lucignani, C Rossetti, F Fazio, D Giudici, V di Carlo, M Cristallo, G Pozza, A Secchi
Journal: Diabetes Care (2000)

OBJECTIVE: Diastolic function is frequently impaired in diabetic patients. Our aim was to evaluate the effects of glycometabolic control achieved by pancreas transplantation on left ventricular function in uremic type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Left ventricular systolic and diastolic functions were evaluated using radionuclide ventriculography in 42 kidney-pancreas transplant patients and 26 kidney-alone recipients who had similar clinical characteristics before transplantation. Patients were grouped according to 6, 24, and 48 months of follow-up. Control subjects consisted of 20 type 1 diabetic patients. RESULTS: The left ventricular ejection fraction was normal in all of the patients. However, kidney-pancreas transplant patients with 4 years of graft function had a higher ejection fraction (75.7 +/- 1.8%) than kidney-alone patients with 4 years of graft function (65.3 +/- 2.8%, P = 0.02) and type 1 diabetic patients (61.3 +/- 3.7%, P = 0.004). In patients with 4 years of graft function, normal diastolic parameters were evident in kidney-pancreas but not in kidney-alone or in type 1 diabetic patients (peak filling rate: 4.46 +/- 0.15 end diastolic volume (EDV)/s in kidney-pancreas patients vs. 2.73 +/- 0.24 EDV/s [P &amp;lt; 0.01] and 3.39 +/- 0.30 EDV/s [P &amp;lt; 0.01] in kidney-alone and type 1 diabetic patients, respectively; time-to-peak filling rate: 141.9 +/- 7.8 ms in kidney-alone patients vs. 209.4 +/- 13.5 ms in kidney-alone patients [P &amp;lt; 0.01]; peak filling rate/peak ejection rate ratio: 1.10 +/- 0.04 in kidney-pancreas patients vs. 0.81 +/- 0.08 in kidney-alone patients [P &amp;lt; 0.01]). A significant reduction in diastolic dysfunction rate was observed only in kidney-pancreas patients. CONCLUSIONS: Kidney-pancreas transplantation results in complete insulin independence, a better glycometabolic pattern and blood pressure control, an improvement of left ventricular function, and a reversal of diastolic dysfunction.
IL-5 production by bronchoalveolar lavage and peripheral blood mononuclear cells in asthma and atopy
Authors: C Tang, JM Rolland, C Ward, B Quan, EH Walters
Journal: European Respiratory Journal (1997)

There is increasing evidence to suggest a key role for interleukin-5 (IL-5) in the regulation of airway eosinophilia in asthma. We compared the capacity for IL-5 production in atopic asthmatic, nonatopic asthmatic, atopic nonasthmatic and normal subjects, and evaluated the usefulness of peripheral blood cells for reflecting airway cell reactivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics (without inhaled steroid therapy), 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite (HDM, 10 microg x mL-1) stimulation. CD4+ T-cell activation, IL-5 and interferon-gamma (IFN-gamma) production in the cultures were assessed. Both for BAL and PBMC samples, atopic and nonatopic asthmatic subjects showed comparable spontaneous production of IL-5, which was significantly higher than that either for atopic nonasthmatics or normal controls (p<0.05 or p<0.01). There was a significant correlation between the percentage of eosinophils in BAL and spontaneous production of IL-5 by BAL cells in both asthmatic groups (p<0.05 or p<0.01). Both these parameters were also associated with asthmatic airway narrowing as denoted by a negative relationship with baseline forced expiratory volume in one second (FEV1) as percentage predicted (p<0.05 and p<0.01, respectively). In contrast, IFN-gamma production by unstimulated BAL cells from normal controls was higher than that for BAL cell cultures of nonatopic asthmatic subjects (p<0.05). Following HDM stimulation, both atopic groups had comparable positive responses in terms of CD4+ T-cell activation, but there was relatively greater IL-5 production in asthmatic PBMC (p<0.05) and, in particular, BAL cell cultures (p<0.01). These findings suggest that elevated IL-5 production is a common feature of BAL cells and PBMC in atopic and nonatopic asthma. In addition, atopic asthmatics show greater IL-5 production in response to specific allergen compared with atopic nonasthmatics, an effect most marked in BAL cells compared to PBMC. Hence, peripheral blood mononuclear cells can reflect cytokine immunoreactivity of airway cells, but lack local cellular interactions, which limits their usage in asthma research.
Large-Scale Characterization of DNA Methylation Changes in Human Gastric Carcinomas with and without Metastasis
Authors: Zhaojun Liu, Jun Zhang, Yanhong Gao, Lirong Pei, Jing Zhou, Liankun Gu, Lianhai Zhang, Budong Zhu, Naoko Hattori, Jiafu Ji, Yasuhito Yuasa, Wooho Kim, Toshikazu Ushijima, Huidong Shi, Dajun Deng
Journal: Clinical Cancer Research (2014)

Metastasis is the leading cause of death for gastric carcinoma. An epigenetic biomarker panel for predicting gastric carcinoma metastasis could have significant clinical impact on the care of patients with gastric carcinoma. The main purpose of this study is to characterize the methylation differences between gastric carcinomas with and without metastasis.
Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Authors: Marta Agostinho, Vera Santos, Fernando Ferreira, Rafael Costa, Joana Cardoso, Inês Pinheiro, José Rino, Ellis Jaffray, Ronald T. Hay, João Ferreira
Journal: Cancer Research (2008)

Abstract Type 2 topoisomerases, in particular the α isoform in human cells, play a key role in cohesion and sister chromatid separation during mitosis. These enzymes are thus vital for cycling cells and are obvious targets in cancer chemotherapy. Evidence obtained in yeast and Xenopus model systems indicates that conjugation of topoisomerase 2 with small ubiquitin-like modifier (SUMO) proteins is required for its mitotic functions. Here, we provide biochemical and cytologic evidence that topoisomerase 2α is conjugated to SUMO-2/3 during interphase and mitosis in response to topoisomerase 2 inhibitors and “poisons” (ICRF-187, etoposide, doxorubicin) that stabilize catalytic intermediates (cleavage complexes, closed clamp forms) of the enzyme onto target DNA. During mitosis, SUMO-2/3–modified forms of topoisomerase 2α localize to centromeres and chromosome cores/axes. However, centromeres are unresponsive to inhibitors during interphase. Furthermore, formation of topoisomerase 2α–SUMO-2/3 conjugates within mitotic chromosomes strongly correlates with incomplete chromatid decatenation and decreases progressively as cells approach the metaphase-anaphase transition. We also found that the PIASy protein, an E3 ligase for SUMO proteins, colocalizes with SUMO-2/3 at the mitotic chromosomal cores/axes and is necessary for both formation of SUMO-2/3 conjugates and proper chromatid segregation. We suggest that the efficacy of topoisomerase inhibitors to arrest cells traversing mitosis may relate to their targeting of topoisomerase 2α–SUMO-2/3 conjugates that concentrate at mitotic chromosome axes and are directly involved in chromatid arm separation. [Cancer Res 2008;68(7):2409–18]