tbuckley/cabot-search huggingface dataset:
Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma†
Authors: Dong‐Jiang Tang, Sui‐Sui Dong, Ning‐Fang Ma, Dan Xie, Leilei Chen, Li Fu, Sze Hang Lau, Yan Li, Yan Li, Xin‐Yuan Guan
Journal: Hepatology (2009)

A high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by down-regulation of epithelial markers (E-cadherin and β-catenin) and up-regulation of mesenchymal markers (fibronectin, N-cadherin, α-SMA, and vimentin). In addition, EIF5A2 could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. Conclusion: EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. (HEPATOLOGY 2010.)
Acetylsalicylic acid in the prevention of early stenosis and occlusion of transjugular intrahepatic portal-systemic stent shunts: A controlled study
Authors: Lorenz Theilmann, Peter Sauer, Thomas Roeren, Gerd Otto, Joachim C. Arnold, Gerd Noeldge, Goetz Richter, Adolf Stiehl
Journal: Hepatology (1994)

Stenosis or occlusion of the transjugular intrahepatic portal-systemic stent shunt may be initiated by aggregation and activation of thrombocytes on the surface of the metallic stent material. To find effective prevention of this event, we conducted a controlled trial administering acetylsalicylic acid for 3 mo. Forty-four patients (8 women and 36 men) with portal hypertension were included in this study. The patients were randomized into a group receiving 100 mg acetylsalicylic acid/day (n = 21) or into a control group (n = 23). Treatment was started immediately after transjugular intrahepatic portal-systemic stent shunt. Three months after transjugular intrahepatic portal-systemic stent shunt, 15 patients in the acetylsalicylic acid group and 19 patients in the control group underwent clinical reevaluation, gastroscopy and recatheterization with determination of the portal-systemic pressure gradient. No variceal bleeding occurred in any patients. In four patients in the acetylsalicylic acid group, erosive gastritis was observed in gastroscopy in contrast to only one patient in the control group. Complete patency of the stent was noted in 10 of 15 patients in the acetylsalicylic acid group and in 14 of 19 patients in the control group. Transjugular intrahepatic portal-systemic stent shunt restenosis associated with a significant increase of the portal-systemic gradient occurred in five patients in the acetylsalicylic acid group, which required redilation in all and additional stent placement for expansion of the stented tract in two patients. In the control group, redilation was necessary in five patients with additional stent extension in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)
High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study
Authors: Ane L Appelt, John Pløen, Henrik Harling, Frank S Jensen, Lars H Jensen, Jens C R Jørgensen, Jan Lindebjerg, Søren R Rafaelsen, Anders Jakobsen
Journal: The Lancet Oncology (2015)
T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice.
Authors: A Ma, M Datta, E Margosian, J Chen, I Horak
Journal: The Journal of Experimental Medicine (1995)

Interleukin-2 (IL-2)-deficient (IL-2-/-) mice develop anemia and colonic inflammatory bowel disease. To elucidate the mechanism of this disease, we have bred IL-2-/- mice to two strains of immunodeficient mice, RAG-2-deficient (RAG-2-/-, lacking B and T cells) and JH-deficient mice (JH-/-, lacking B cells). IL-2-/-, RAG-2-/- double-mutant mice are disease free, while IL-2-/-, JH-/- double-mutant mice succumb to bowel disease at the same rate as IL-2-/- littermates. IL-2-/-, JH-/- mice do not, however, succumb to anemia. Thus, spontaneous intestinal inflammation in IL-2-/- mice requires mature T cells, not B cells, while anemia is dependent on B cells.
In utero smoke exposure and impaired response to inhaled corticosteroids in children with asthma
Authors: Robyn T. Cohen, Benjamin A. Raby, Kristel Van Steen, Anne L. Fuhlbrigge, Juan C. Celedón, Bernard A. Rosner, Robert C. Strunk, Robert S. Zeiger, Scott T. Weiss
Journal: Journal of Allergy and Clinical Immunology (2010)
Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches
Authors: Tim F Greten, Xin W Wang, Firouzeh Korangy
Journal: Gut (2015)

The recent approval of two immune checkpoint inhibitors for the treatment of malignant melanoma has sparked great interest by physicians and basic scientists searching for novel therapeutics for GI cancer. Chronic inflammation is recognised as a major risk factor for the development of hepatocellular carcinoma (HCC) and makes this type of cancer a potentially ideal target for an immune based treatment approach. Further evidence for a critical role of immune responses in patients with HCC is derived from the fact that immune signatures and profiles predict patients’ outcome as well as the fact that tumour-induced spontaneous antitumour immunity can be detected. In addition ablative therapies can lead to changes in the number, phenotype and function of different immune cell subsets, which correlate with patients’ survival. Various HCC-specific mouse models have been developed, which improve our understanding of hepatocarcinogenesis and tumour-immune cell interactions, and lead to the development of novel immune based treatment approaches, which are currently being evaluated in preclinical and in early clinical settings. Immune checkpoint blockade along with adoptive immune cell therapy and vaccine approaches are currently being evaluated either alone or in combination with other treatments. Here, we provide an overview for the rationale of immunotherapy in HCC, summarise ongoing studies and provide a perspective for immune based approaches in patients with HCC.
Hypoglycemia Unawareness Is Associated With Reduced Adherence to Therapeutic Decisions in Patients With Type 1 Diabetes: Evidence from a Clinical Audit
Authors: Alex J. Graveling, Brian M. Frier
Journal: Diabetes Care (2009)

Smith et al. (1) have demonstrated that people with type 1 diabetes who have impaired awareness of hypoglycemia (IAH), diagnosed on clinical history alone, are less likely to adhere to therapeutic decisions. This finding is of clinical importance as the syndrome of IAH is often very difficult to manage, and the reluctance …
Defective Relationship Between Subjective Experience and Behavior in Schizophrenia
Authors: Jean-Marie Danion, Erick Gokalsing, Philippe Robert, Marilyne Massin-Krauss, Elisabeth Bacon
Journal: American Journal of Psychiatry (2001)

The relationship between subjective experience and behavior abnormalities in schizophrenia was investigated.Eighteen patients with schizophrenia and 18 normal comparison subjects completed a general knowledge task with two incentive conditions to measure monitoring effectiveness, control sensitivity, and response criterion setting.The patients' levels of monitoring effectiveness and control sensitivity were lower than those of the comparison subjects. The effect of incentives on response criterion values was similar in the two groups.Patients were impaired in subjectively assessing the correctness of their knowledge, and their behavior was less determined by subjective experience than that of normal subjects. The patients' intact sensitivity to incentives has implications for cognitive remediation.
A new endogenous retroviral sequence is expressed in skin of patients with psoriasis
Authors: J-P. Moles, A. Tesniere, J-J. Guilhou
Journal: British Journal of Dermatology (2005)

Journal Article A new endogenous retroviral sequence is expressed in skin of patients with psoriasis Get access J‐P. Molès, J‐P. Molès Laboratoire de Dermatologie Moléculaire, Institut Universitaire de Recherche Clinique, 641 avenue du Doyen G. Giraud, 34093 Montpellier cedex 5, France Jean‐Pierre Molès. E‐mail: dermato@iurc1.iurc.montp.inserm.fr Search for other works by this author on: Oxford Academic Google Scholar A. Tesniere, A. Tesniere Laboratoire de Dermatologie Moléculaire, Institut Universitaire de Recherche Clinique, 641 avenue du Doyen G. Giraud, 34093 Montpellier cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar J‐J. Guilhou J‐J. Guilhou Laboratoire de Dermatologie Moléculaire, Institut Universitaire de Recherche Clinique, 641 avenue du Doyen G. Giraud, 34093 Montpellier cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 1, 1 July 2005, Pages 83–89, https://doi.org/10.1111/j.1365-2133.2005.06555.x Published: 01 July 2005 Article history Accepted: 04 December 2004 Published: 01 July 2005
TRICHOSTASIS SPINULOSA AND ITS MANAGEMENT
Authors: I. SARKANY, P. M. GAYLARDE
Journal: British Journal of Dermatology (1971)

Journal Article TRICHOSTASIS SPINULOSA AND ITS MANAGEMENT Get access I. SARKANY, I. SARKANY Department of Dermatology, Royal Free Hospital, London, W.C.1 Search for other works by this author on: Oxford Academic Google Scholar P. M. GAYLARDE P. M. GAYLARDE Department of Dermatology, Royal Free Hospital, London, W.C.1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 4, 1 April 1971, Pages 311–315, https://doi.org/10.1111/j.1365-2133.1971.tb14224.x Published: 01 April 1971 Article history Accepted: 21 December 1970 Published: 01 April 1971
Interactive Behavior Change Technology to Support Diabetes Self-Management
Authors: John D. Piette
Journal: Diabetes Care (2007)

The number of people living with diabetes continues to rise at an astounding rate (1). Moreover, the epidemic of childhood obesity, coupled with widespread intake of high-fat, low-fiber diets, suggests that this problem will not abate in the foreseeable future (2). Even if the number of diabetic patients miraculously held constant, the need for diabetes medical management and self-care support would continue to trend upward. Diabetes treatment and outcomes have improved over recent years (3–5), and, like the population overall, patients are living longer. Meanwhile, expectations for diabetes care are increasing, with clearer standards for what self-care support should include (which is a good thing [6]), as well as increasingly aggressive goals for physiologic targets such as A1C and blood pressure (which has been more controversial [7,8]). Payers for health services are having an increasingly difficult time funding diabetes care. Experts agree that the current Medicare program will be insolvent in less than 20 years (9), and mounting costs on private insurers have led them to increase cost sharing, limit eligibility and benefits, and even close their doors completely. Insurers pass these financial pressures onto both service providers (through lower payments) and beneficiaries (through higher co-pays and fewer benefits), making out-of-pocket cost one of the major barriers to effective diabetes management (10,11). In short, we now face the untenable situation of a growing demand for diabetes services, coupled with fewer and fewer resources to pay for it.

Meeting this challenge requires addressing some of the most complex problems in health care, including how to coordinate diabetes services across providers and how to provide effective support for self-management between outpatient visits. The Chronic Care Model is now accepted worldwide as a blueprint for how a transformed system of care should look …
Purpuric adult T-cell leukaemia/lymphoma: expansion of unusual CD4/CD8 double-negative malignant T cells expressing CCR4 but bearing the cytotoxic molecule granzyme B
Authors: T. Shimauchi, Y. Hirokawa, Y. Tokura
Journal: British Journal of Dermatology (2005)

A 78-year-old Japanese woman with adult T-cell leukaemia/lymphoma (ATL) presented with an unusual purpuric and erythematous eruption on the face and trunk. Immunohistochemical and flow cytometric analyses showed that the tumour cells were CD4/CD8 double-negative, and expressed CCR4 T-helper (Th) 2 chemokine receptors. Despite these features, the cells aberrantly produced granzyme B, which is a cytotoxic molecule usually produced by CD8+ cytotoxic T cells, natural killer cells, or occasionally by Th1 cells. In a purpuric lesion, extravasation of erythrocytes was associated with an infiltrate of these cytotoxic tumour cells. Our case suggests phenotypical and functional heterogeneity of tumour cells in ATL, which may be closely related to the clinical appearance of the skin eruption.
ACQUIRED IMMUNODEFICIENCY SYNDROME IN FRANCE
Authors: J.B Brunet, E Bouvet, J Chaperon, J.C Gluckman, S Kernbaum, D Klatzmann, D Lachiver, J Leibowitch, C Mayaud, O Picard, J Revuz, W Rozenbaum, J Villalonga, C Wesselberg
Journal: The Lancet (1983)
Combination Antiangiogenic and Androgen Deprivation Therapy for Prostate Cancer
Authors: Brian Nicholson, Kathryn Gulding, Mark Conaway, Stephen R. Wedge, Dan Theodorescu
Journal: Clinical Cancer Research (2004)

Androgen ablation therapy leads to mild regression or stabilization of prostate cancer, followed by progression to the fatal androgen-independent state. Whereas androgen ablation diminishes tumor angiogenesis by suppressing vascular endothelial growth factor (VEGF) production, androgen-independent disease is marked by androgen-independent VEGF expression. We examined combined androgen ablation and inhibition of VEGF signaling in an androgen-sensitive human prostate cancer xenograft model (LNCaP) that is known to develop androgen-independent growth after androgen ablation.N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine (ZD6474) is an orally active inhibitor of VEGF receptor tyrosine kinase activity, with additional activity against epidermal growth factor receptor tyrosine kinase. ZD6474 (50 mg/kg/d, per os) was administered to groups of castrated and noncastrated athymic mice bearing established (4-616 mm3) LNCaP xenografts. To evaluate the extent of tumor regrowth after ZD6474, treatment was stopped after 40 days of continuous dosing, and subsequent tumor growth was monitored. Prostate-specific antigen expression was assessed to determine the effect of ZD6474 on androgen-regulated genes.In comparison with orchiectomy, ZD6474 treatment produced greater tumor growth inhibition (P < 0.001), inducing complete cytostasis for the duration of dosing. An analysis of serum prostate-specific antigen concentration and tumor weight indicated that ZD6474 did not have a direct effect on androgen-related gene expression. Combination therapy (castration plus ZD6474) produced a comparable therapeutic effect to treatment with ZD6474 alone (in noncastrated mice), for the duration of ZD6474 administration. However, when ZD6474 treatment was discontinued, the rate of tumor regrowth was significantly less in the combination group. Tumors from mice receiving combined treatment were also found to be more necrotic than tumors from mice receiving either androgen ablation or ZD6474 alone.These data indicate that inhibition of VEGF signaling produces a highly significant inhibition of tumor growth in a human androgen-dependent prostate tumor model, which far exceeds that produced by androgen ablation alone. However, when ZD6474 treatment is removed, concurrent androgen ablation produces a greater inhibition of tumor regrowth than is observed in mice without androgen ablation. Increased necrosis observed in tumors from orchiectomized mice receiving ZD6474 also suggests benefit from combining anti-androgen and anti-VEGF signaling approaches.
Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma
Authors: Peter S Harris, Sujatha Venkataraman, Irina Alimova, Diane K Birks, Ilango Balakrishnan, Brian Cristiano, Andrew M Donson, Adrian M Dubuc, Michael D Taylor, Nicholas K Foreman, Philip Reigan, Rajeev Vibhakar
Journal: Molecular Cancer (2014)

Medulloblastoma is the most common type of malignant brain tumor that afflicts children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients do poorly with significant morbidity. To identify new molecular targets, we performed an integrated genomic analysis using structural and functional methods. Gene expression profiling in 16 medulloblastoma patient samples and subsequent gene set enrichment analysis indicated that cell cycle-related kinases were associated with disease development. In addition a kinome-wide small interfering RNA (siRNA) screen was performed to identify kinases that, when inhibited, could prevent cell proliferation. The two genome-scale analyses were combined to identify key vulnerabilities in medulloblastoma. The inhibition of one of the identified targets was further investigated using RNAi and a small molecule inhibitor. Combining the two analyses revealed that mitosis-related kinases were critical determinants of medulloblastoma cell proliferation. RNA interference (RNAi)-mediated knockdown of WEE1 kinase and other mitotic kinases was sufficient to reduce medulloblastoma cell proliferation. These data prompted us to examine the effects of inhibiting WEE1 by RNAi and by a small molecule inhibitor of WEE1, MK-1775, in medulloblastoma cell lines. MK-1775 inhibited the growth of medulloblastoma cell lines, induced apoptosis and increased DNA damage at nanomolar concentrations. Further, MK-1775 was synergistic with cisplatin in reducing medulloblastoma cell proliferation and resulted in an associated increase in cell death. In vivo MK-1775 suppressed medulloblastoma tumor growth as a single agent. Taken together, these findings highlight mitotic kinases and, in particular, WEE1 as a rational therapeutic target for medulloblastoma.
Ultrastructural and immunohistochemical studies on the ontogenic development of bronchus-associated lymphoid tissue (BALT) in the rat: special reference to follicular dendritic cells
Authors: Y Matsuura, T Matsuoka, Y Fuse
Journal: European Respiratory Journal (1992)

The ontogenic development of lymphoid and non-lymphoid cells in bronchus-associated lymphoid tissue (BALT) of the rat was studied ultrastructurally and immunohistochemically. In the late foetal period, only the alveolar macrophages showed a weak positivity for leucocyte common antigen, but no immune region associated (Ia) antigen was detected by monoclonal antibody, MAS 043. Mast cells were present. At 6 days of age, Ia-positive cells were observed in the alveolar wall and peribronchial interstitial tissue, and ultrastructurally there was an aggregation of the fibroblastoid mesenchymal cells. By 10 days of age, the aggregation of lymphoid cells together with S-100-positive reticulum cells had formed a BALT-like periarterial lymphoid sheath. In the adult animals, an obvious B-cell area was present in the central part and subepithelium of BALT, whilst in this area, S-100-positive, strongly Ia-positive cells with a dendritic form were observed. These dendritic cells appeared to be identical to the follicular dendritic cells (FDC) seen in the secondary follicles of lymphoid organs. Those cells may be derived from the fibroblastic reticulum cells, and may function to present antigen to lymphocytes.
Evidence for antigenicity in human tumours with reference to both melanoma and acute leukaemia.
Authors: G. H. Fairley
Journal: BMJ (1970)

There is now no doubt that tumour-associated antigens exist in experimental animal tumours, and that immunological reactions against these antigens can influence the course of the malignant disease.'Because of the difficulties of research in man, the situation is not as clear as in animals.Nevertheless, recent work has shown that tumour-associated antigens are present in human malignant tissue.The two diseases selected for special discussion are malignant melanoma and acute leukaemia. Malignant MelanomaFor many years evidence has been accumulating that there may be a host reaction to malignant melanoma and that this reaction could be immunological.Firstly, melanoma is one of the malignant diseases which occasionally undergoes spon- taneous regression.'-8Secondly, the disease may remain localized for a long time before it becomes disseminated.9 1" Thirdly, even in patients with disseminated disease some metastatic deposits can regress at the same time as new ones appear and others continue to grow."Fourthly, Lewis" has shown in Ugandan patients that those with localized tumours often had cytotoxic serum antibody active only against the patient's own melanoma cells.This suggested that there may be tumour-specific antigens in melanoma similar to those found in chemically induced tumours in animals.Correlation of the Stage of Malignant Melanoma with Presence of Tumour-Specific Cytotoxic Autoantibodies No. of Having Patients Auto-antibodies Localized disease* . . .
Mesenchymal CD44 Expression Contributes to the Acquisition of an Activated Fibroblast Phenotype via TWIST Activation in the Tumor Microenvironment
Authors: Erika L. Spaeth, Adam M. Labaff, Bryan P. Toole, Ann Klopp, Michael Andreeff, Frank C. Marini
Journal: Cancer Research (2013)

Abstract Tumor–stroma interactions play a crucial role in cancer progression by eliciting factors that promote proliferative, angiogenic, and invasive supports to the tumor microenvironment. Mesenchymal stromal/stem cells (MSC) contribute to stroma in part as cancer-associated fibroblasts (CAF), but a complete understanding of how MSC contribute to the tumor stroma is lacking. In this study, we show how CAF phenotypes rely upon MSC expression of the multifunctional cell surface glycoprotein CD44, a putative stem cell marker. Through bone marrow transplantation experiments in a transgenic mouse model of cancer, we determined that CD44 deficiency leads to a relative reduction in the contribution of bone marrow–derived cells to tumor stroma. CD44 attenuation in MSC limited their expression of CAF markers induced by tumor conditioning, and these MSC migrated poorly and provided weak angiogenic support compared with wild-type MSC. These defects were linked to deficiencies in the ability of CD44-attenuated MSC to transcriptionally upregulate Twist expression. Together, our results establish that CD44 expression contributes to critical functions in the tumor stroma. Cancer Res; 73(17); 5347–59. ©2013 AACR.
The Cost of Breast Cancer Screening in the Medicare Population
Authors: Cary P. Gross, Jessica B. Long, Joseph S. Ross, Maysa M. Abu-Khalaf, Rong Wang, Brigid K. Killelea, Heather T. Gold, Anees B. Chagpar, Xiaomei Ma
Journal: JAMA Internal Medicine (2013)

Little is known about the cost to Medicare of breast cancer screening or whether regional-level screening expenditures are associated with cancer stage at diagnosis or treatment costs, particularly because newer breast cancer screening technologies, like digital mammography and computer-aided detection (CAD), have diffused into the care of older women.