bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADH‐1 suppresses N‐cadherin‐dependent pancreatic cancer progression
Authors: Shintani Yasushi , Fukumoto Yuri , Chaika Nina , Grandgenett Paul M. , Hollingsworth Michael A. , Wheelock Margaret J. , Johnson Keith R. 
Published: August 2007

AbstractPancreatic cancer is one of the most aggressive malignant diseases. We recently reported that N‐cadherin plays a key role in tumor progression and metastasis in pancreatic cancer. For this study, we sought to determine if an N‐cadherin‐blocking peptide (ADH‐1) could prevent N‐cadherin‐mediated tumor progression in a mouse model for pancreatic cancer. The effect of ADH‐1 on N‐cadherin‐mediated cell scattering and migration on collagen I was examined using pancreatic cancer cells. We also examined the influence of ADH‐1 on cell apoptosis. Furthermore, in vivo animal studies were performed using orthotopic injection of N‐cadherin overexpressing BxPC‐3 cells with or without ADH‐1 treatment. BxPC‐3 and Capan‐1 cells exhibited increased expression of N‐cadherin in response to collagen I. This increase in N‐cadherin promoted cell scattering and migration in response to collagen I. ADH‐1 prevented these changes, but did not inhibit upregulation of N‐cadherin. TUNEL assays and immunoblots for caspase‐3 showed that ADH‐1 induced apoptosis in a concentration dependent and N‐cadherin dependent manner in pancreatic cancer cells. ADH‐1 treatment resulted in significant reductions in tumor growth and lung metastasis in a mouse model for pancreatic cancer. The N‐cadherin antagonist, ADH‐1 has significant antitumor activity against N‐cadherin‐expressing cells using in vitro assays and in an orthotopic mouse model for pancreatic cancer, raising the possibility that N‐cadherin antagonists have therapeutic potential for the treatment of pancreatic cancer in humans. © 2007 Wiley‐Liss, Inc.
Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous cell carcinoma
Authors: Patel Heena , Polanco‐Echeverry Guadalupe , Segditsas Stefania , Volikos Emmanouil , McCart Amy , Lai Cecilia , Guenther Thomas , Zaitoun Abed , Sieber Oliver , Ilyas Mohammed , Northover John , Silver Andrew 
Published: August 2007

AbstractHuman papilloma virus (HPV) infection is considered as an important aetiological factor for anal squamous cell carcinoma (ASCC) but is not sufficient for tumour progression. This carcinoma is poorly understood at the molecular level. Using the largest cohort of cases to date we investigated the molecular mechanisms underlying ASCC development, in particular the roles of TP53, MDM2 and AKT. Viral infection in our cohort occured at high frequency (73%, 94/128) with HPV16 accounting for the majority (86%, 81/94) of infected cases. Only 4% (5/119) of ASCCs showed TP53 (exons 5–8) mutations, but a high frequency (91%, 100/110) of nuclear protein expression of TP53 was observed. There was a significant association (p < 0.001) between nuclear accumulation of TP53 and MDM2 protein although no MDM2 mutations were found, and copy number was normal. Cellular accumulation of phosphorylated‐AKT was observed in 66% (82/125) of ASCCs and an association demonstrated between nuclear accumulation of MDM2 and activated AKT (p < 0.001). We observed a high frequency of copy number gain at PIK3CA (47%), and some coding sequence mutations (4%). Amplification of PIK3CA was associated with presence of phosphorylated‐AKT (p= 0.008). There was no association between virus infection and TP53 nuclear accumulation (p = 0.5). However, a significant association was found between infection and MDM2 nuclear staining, and between infection and activated AKT (p = 0.04, p = 0.01, respectively). We propose that activation of AKT, possibly through the PI3K‐AKT pathway, is an important component of ASCC tumorigenesis that contributes to MDM2 and TP53 accumulation in the nucleus. © 2007 Wiley‐Liss, Inc.
Imatinib inhibits colorectal cancer cell growth and suppresses stromal‐induced growth stimulation, MT1‐MMP expression and pro‐MMP2 activation
Authors: Stahtea Xanthi N. , Roussidis Andeas E. , Kanakis Ioannis , Tzanakakis George N. , Chalkiadakis George , Mavroudis Dimitris , Kletsas Dimitris , Karamanos Nikos K. 
Published: August 2007

AbstractTumor progress depends on the proliferation of cancer cells, their interactions with stroma and the proteolytic action of enzymes. Colon cancer is c‐kit positive and responsive to the specific tyrosine kinase inhibitor imatinib. We investigated the effect of imatinib on the proliferation of a panel of epithelial colon cancer cell lines in presence and absence of the antimetabolite 5‐FU, and the effect of conditioned media (CM) derived from colon stromal fibroblasts with and without previous exposure to imatinib. The effects of imatinib on gene expression of MMPs and TIMPs were also studied. Imatinib effectively inhibited the proliferation of all cell lines, showing IC50 from 0.3 to 3 μM. Its combination with 5‐FU significantly enhances the growth inhibition of the highly tumourigenic HT‐29 cells. CM derived from stromal fibroblasts induced the proliferation of the HT‐29 cells; this stimulatory effect was abolished upon treatment with CM obtained after exposure of fibroblasts to imatinib. Gene expression of MT1‐, MT2‐MMP and MMP‐7 was also inhibited depending on the cell line, whereas that of TIMP‐2 was not affected. CM stimulated MT1‐MMP protein expression by HT‐29; this stimulatory effect was suppressed in the presence of imatinib. Activation of pro‐MMP2 to MMP2 in culture medium of HT‐29 treated with CM was increased and this activity was inhibited in presence of imatinib. The obtained data showed that imatinib is a powerful inhibitor of human colon cancer cell growth and effectively suppresses the stromal‐induced stimulation of cancer cell growth and activation of proMMP2. Further studies are warranted to evaluate the in vivo effects. © 2007 Wiley‐Liss, Inc.
S‐adenosyl L‐methionine inhibits azoxymethane‐induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco‐2 cell growth in 3D culture
Authors: Guruswamy Suresh , Swamy Malisetty V. , Choi Chang‐In , Steele Vernon E. , Rao Chinthalapally V. 
Published: August 2007

AbstractS‐Adenosyl L‐methionine (SAM) is a universal methyl group donor to various intermediary metabolites, hormones, proteins, neurotransmitters, phospholipids and nucleic acids. Deficiency of folate, which plays a role in the synthesis of SAM leads to increased risk for colon cancer. This study tested the effectiveness of SAM supplementation in protecting against azoxymethane (AOM)‐induced colon carcinogenesis in male F344 rats. We also tested the effect of SAM on cyclooxygenase‐2 (COX‐2) in a macrophage cell line. Further, we developed a 3‐D culture model using Caco‐2 cells to test the effect of SAM on tumor spheroid size and number. Groups of rats were given the experimental diet containing either 0‐, 400‐ or 800‐ppm SAM, 1 week before the first AOM injection and continued until 8 weeks. In the control group, AOM produced a substantial number of aberrant crypt foci (ACF) (96 ± 8). Dietary administration of SAM significantly reduced the number of total ACF (400 ppm SAM, 68 ± 7.3, p < 0.01 and 800 ppm SAM, 57 ± 7.1, p < 0.001). SAM significantly decreased AOM‐induced colonic multicrypt foci in a dose‐dependent manner. Suppression of Lipopolysaccharide (LPS) induced COX‐2 protein expression was observed in a RAW264.7 cell line. We established growth of Caco‐2 cells as spheroids, in a 3D matrix of collagen and matrigel. Treatment with SAM decreased both size and number of spheroids in a dose‐dependent manner (p < 0.0001). These observations demonstrate for the first time that SAM can reduce the occurrence of ACF in AOM treated male F344 rats and suppress formation of human tumor spheroids and expression of COX‐2. © 2007 Wiley‐Liss, Inc.
Acne and risk of prostate cancer
Authors: Sutcliffe Siobhan , Giovannucci Edward , Isaacs William B. , Willett Walter C. , Platz Elizabeth A. 
Published: August 2007

AbstractIn a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture‐negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes‐mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for 4 or more years, in relation to incident prostate cancer in the Health Professionals Follow‐up Study. On the 1992 follow‐up questionnaire, participants were asked whether they had ever used “tetracycline for at least 2 months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for 4 or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person‐years) than men who did not use tetracycline (2,071 cases, 304,822 person‐years, multivariable‐adjusted RR = 1.70, 95% CI: 1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis. © 2007 Wiley‐Liss, Inc.
Family history of urogenital cancers in patients with bladder, renal cell and prostate cancers
Authors: Randi Giorgia , Pelucchi Claudio , Negri Eva , Talamini Renato , Galeone Carlotta , Franceschi Silvia , La Vecchia Carlo 
Published: August 2007

AbstractFamily history of urogenital cancers has been associated with an increased risk of cancer at the same sites. To evaluate the risks of bladder, prostate and renal cell neoplasms for family history of urogenital cancers in first‐degree relatives, we analysed data from a case‐control study conducted in northern Italy between 1985 and 1992 and including a total of 1,356 incident, histologically confirmed cancer cases: 727 bladder, 348 renal cell and 281 prostate cancer cases. Controls were 1,067 patients admitted to the same network of hospitals for acute, nonneoplastic conditions. Unconditional logistic regression was used to estimate odds ratios (ORs) of urogenital cancers, adjusting for age, sex, study centre, education, body mass index, smoking habit, alcohol consumption and number of brothers and, where appropriate, sisters. ORs of urogenital cancers for subjects with at least 1 first‐degree relative with cancer at the same site were 6.1 [95% confidence interval (CI), 2.3–16.6] for bladder, 2.0 (95% CI: 0.6–6.2) for renal cell and 2.0 (95% CI: 0.9–4.1) for prostate cancer. © 2007 Wiley‐Liss, Inc.
Osteonectin downregulates E‐cadherin, induces Osteopontin and Focal adhesion kinase activity stimulating an invasive melanoma phenotype
Authors: Smit Darren J. , Gardiner Brooke B. , Sturm Richard A. 
Published: August 2007

AbstractOsteonectin is recognised as a marker of metastasis progression in melanoma and has been implicated in the transition from radial to vertical growth phase. A Tetracycline‐inducible system was used to regulate Osteonectin protein levels in melanoma cell lines to examine the morphological, biochemical and invasive changes that accompany its altered expression. Assay of protein and phosphorylation changes showed a downregulation of E‐cadherin, upregulation of Osteopontin and a corresponding increase in phosphorylation of Focal Adhesion Kinase on Tyr397 and Tyr576 concomitant with Osteonectin induction. Melanoma cells overexpressing Osteonectin displayed increased invasive potential, whereas ablation of Osteonectin gene transcription using siRNA suppressed the invasive potential of these cells and resulted in the upregulation of E‐cadherin. The recently described interaction of Osteonectin with Integrin Linked Kinase leading to modulation of its activity suggests a mechanism relevant to the loss of E‐cadherin and cell adhesion that occurs during melanoma progression. These results indicate a central role for Osteonectin in the regulation of gene expression changes driving the progression of melanoma toward metastasis. © 2007 Wiley‐Liss, Inc.
Augmented expression of programmed death‐1 in both neoplastic and non‐neoplastic CD4+ T‐cells in adult T‐cell leukemia/lymphoma
Authors: Shimauchi Takatoshi , Kabashima Kenji , Nakashima Daiki , Sugita Kazunari , Yamada Yoko , Hino Ryosuke , Tokura Yoshiki 
Published: August 2007

AbstractAdult T‐cell leukemia/lymphoma (ATL) is a CD4+CD25+ T‐cell malignancy infected with human T‐cell leukemia virus type‐I (HTLV‐I). HTLV‐I infection causes the T‐cell dysfunction, which contributes to the immunodeficient state of the patients. Programmed death‐1 (PD‐1) can negatively regulate T‐cell response, when its ligand, PD‐L1 or PD‐L2 mainly expressed on antigen presenting cells, binds to this B7 family receptor. We investigated whether PD‐1 is expressed on CD4+ neoplastic (and/or non‐neoplastic) cells or CD8+ cytotoxic cells in peripheral blood mononuclear cells from 11 patients with ATL. By flow cytometry, we found that the levels of PD‐1 expression on both CD4+CD25+ and CD4+CD25− T‐cell populations were increased in ATL patients compared to normal healthy volunteers, while PD‐1 levels on CD8+ T‐cells were comparable between the patients and normal subjects. In stimulation with anti‐CD3 antibody, the proliferation of PD‐1‐expressing T‐cells from ATL patients was weak when compared to that of PD‐1‐nonexpressing normal T‐cells. In addition to PD‐1, PD‐L1 was coexpressed on ATL cells in some patients, and PD‐L1 expression was enhanced by stimulation with anti‐CD3 antibody. Finally, the production of cytokines such as TNF‐α by ATL cells was restored by blockade of PD‐1/PD‐L1 interaction. These findings suggest that CD4+ T‐cells are the main PD‐1‐expressing cells rather than CD8+ T‐cells in ATL patients, and both neoplastic and normal CD4+ cells are exhausted as a result of PD‐1 expression, and additionally PD‐L1 expression on the neoplastic cell. © 2007 Wiley‐Liss, Inc.
The metastatic T‐cell hybridoma antigen/P‐selectin glycoprotein ligand 1 is required for hematogenous metastasis of lymphomas
Authors: Raes Geert , Ghassabeh Gholamreza Hassanzadeh , Brys Lea , Mpofu Nonsikelelo , Verschueren Hendrik , Vanhecke Dominique , De Baetselier Patrick 
Published: August 2007

AbstractUsing variants of the murine BW5147 lymphoma cell‐line, we have previously identified 3 monoclonal antibodies (MAbs) that discriminate between metastatic and nonmetastatic BW5147‐derived T‐cell hybridomas and lymphomas, as well as BW5147‐unrelated T‐lymphomas. These MAbs were reported to recognize an identical membrane‐associated sialoglycoprotein, termed “metastatic T‐cell hybridoma antigen” (MTH‐Ag). Here, we document that the expression pattern of the MTH‐Ag on metastatic and nonmetastatic BW5147 variants correlates with that of the P‐selectin glycoprotein ligand 1 (PSGL‐1), a sialomucin involved in leukocyte recruitment to sites of inflammation. Moreover, the MAbs against the MTH‐Ag recognize PSGL‐1 when it is transfected in MTH‐Ag‐negative BW5147 variants, suggesting that the MTH‐Ag is PSGL‐1. Overexpression of MTH‐Ag/PSGL‐1 in MTH‐Ag‐negative BW5147 variants did not affect their in vivo malignancy. Yet, down‐regulation of MTH‐Ag/PSGL‐1 expression on metastatic, MTH‐Ag‐positive BW5147 variants, using an RNA interference (RNAi) approach, resulted, in a dose‐dependent manner, in a significant reduction of liver and spleen colonization and a delay in mortality of the recipient mice upon intravenous inoculation. Collectively, these results demonstrate that, although MTH‐Ag/PSGL‐1 overexpression alone may not be sufficient for successful dissemination and organ colonization, MTH‐Ag/PSGL‐1 plays a critical role in hematogenous metastasis of lymphoid cancer cells. © 2007 Wiley‐Liss, Inc.
Continuous infusion of calcium gluconate in 5% albumin is safe and prevents most hypocalcemic reactions during therapeutic plasma exchange
Authors: Kankirawatana Suthida , Huang Shu T. , Marques Marisa B. 
Published: August 2007

AbstractWhile therapeutic plasma exchanges (TPEs) performed with 5% albumin are considered safe, concerns regarding venous access and hypocalcemic toxicity remain. We reviewed the frequency of complications during TPEs performed with 5% albumin supplemented with calcium gluconate and potassium chloride for a 5 year period in our institution. Eighty‐four adult patients (46 males and 38 females) underwent 581 plasma exchanges during the study period. The most common indications were myasthenia gravis (37%), acute inflammatory demyelinating polyradiculoneuropathy (31%), and chronic inflammatory demyelinating polyneuropathy (13%). All procedures used 2.2% ACD‐A delivered at a calculated average rate of 0.26 mg/kg/min, which led to a mean dose of citrate per TPE of 2.18 ± 0.48 g or 27.8 ± 5.24 mg/kg of body weight. Venous access difficulties occurred in 85 procedures (14.6%), but most TPEs were completed successfully. Hypotension and citrate toxicity were seen in <5% of the TPEs and were mostly reversible. Only 17 exchanges (3%) had to be aborted because of the loss of venous access (n = 9), hypocalcemic toxicity (n = 3), hypotension (n = 2), panic attacks (n = 2), and one atypical reaction due to the interaction with an angiotensin converting enzyme inhibitor. Comparison between pre‐ and post‐TPE potassium levels showed a statistically significant mean decrease of 7%, from 4.1 mequiv/l to 3.8 mequiv/l (P < 0.0001). We attribute the low rate of hypocalcemia to our practice of adding calcium and potassium to the replacement fluid and suggest that this method could become standard of care. J. Clin. Apheresis, 2007. © 2007 Wiley‐Liss, Inc.
Complications of therapeutic plasma exchange: A prospective study of 1,727 procedures
Authors: Shemin Douglas , Briggs Doris , Greenan Melanie 
Published: August 2007

AbstractThe type and number of complications was prospectively examined in 1,727 successive TPE treatments in 174 patients over 66 months at a single center. Most treatments were prescribed for thrombotic thrombocytopenic purpura (TTP; 42%), recurrent focal segmental glomerulosclerosis (FSGS; 22%), or myasthenia gravis (MG; 13%). About 57% of treatments used albumin–saline as the replacement solution and 43% used fresh‐frozen plasma (FFP), almost all for TTP. There were 889 complications; 614 treatments (36% of the total) involved a complication. Most complications were minor; there were no deaths. Three treatments (0.2%) were discontinued due to a complication, and 2 (0.1%) required transfer to a higher acuity hospital bed. The most common complications were fever (7.7% of treatments), urticaria (7.4%), and hypocalcemic symptoms (7.3%). 42% of treatments with FFP involved a complication, compared to 30% of treatments using albumin–saline (P < 0.0001). The most common complications with FFP were urticaria (17%) and pruritis (13%); these occurred more commonly than in patients receiving albumin–saline. The most common complications with albumin–saline replacement were hypocalcemic symptoms (8.2%) and mild hypotension (8.1%). Mild and severe hypotension was significantly (P < 0.0001) more common with albumin–saline replacement. TPE is associated with a number of minor complications. Complications occur more commonly with FFP replacement compared to albumin–saline replacement. Pruritis and urticaria occur more commonly with FFP, and hypotension occurs more commonly with albumin–saline. J. Clin. Apheresis, 2007. © 2007 Wiley‐Liss, Inc.
New guidance on executive compensation disclosures
Authors: Rouse Robert W. , Weirich Thomas R. 
Published: August 2007

AbstractThe issue of executive compensation upsets many stockholders. They don't think there is enough information about the process of compensating top management. And they feel they have very little influence over it.Now the Securities and Exchange Commission has stepped into the fray, beefing up the disclosure requirements for executive compensation. What are the key features of the new rules? © 2007 Wiley Periodicals, Inc.
Experimental budgeting research: Implications for practitioners
Authors: Fisher Joseph G. , Sprinkle Geoffrey B. , Walker Lynda L. 
Published: August 2007

AbstractIn most organizations, budgeting is an essential business process. While budgets have many advantages, they have been criticized for discouraging creativity and innovation, destroying cooperation, promoting a short‐term focus, and encouraging gaming. We believe that a well‐designed budgeting system can address many of these concerns. Our belief stems partly from the results of experimental research on budgeting. The purpose of this article is to detail results from some of the recent experimental academic literature on budgeting and to provide insights on budget design and use. This article highlights results from recent academic research on budgeting and summarizes considerations for practitioners as they design and use budgeting systems. © 2007 Wiley Periodicals, Inc.
Back to business with IT governance
Authors: Reznik Steve 
Published: August 2007

AbstractThis article is a complete, corrected reprint and erratum of the article which was originally published in Journal of Corporate Accounting and Finance 18(5), July–August 2007, 57–64.Recent surveys continue to show a serious weakness in how corporate executives and boards are involving themselves with critical IT risks. © 2007 Wiley Periodicals, Inc.
The role of chromosomal alterations in human cancer development
Authors: Gasparini Patrizia , Sozzi Gabriella , Pierotti Marco A. 
Published: August 2007

AbstractCancer cells become unstable and compromised because several cancer‐predisposing mutations affect genes that are responsible for maintaining the genomic instability. Several factors influence the formation of chromosomal rearrangements and consequently of fusion genes and their role in tumorigenesis. Studies over the past decades have revealed that recurring chromosome rearrangements leading to fusion genes have a biological and clinical impact not only on leukemias and lymphomas, but also on certain epithelial tumors. With the implementation of new and powerful cytogenetic and molecular techniques the identification of fusion genes in solid tumors is being facilitated. Overall, the study of chromosomal translocations have revealed several recurring themes, and reached important insights into the process of malignant transformation. However, the mechanisms behind these translocations remain unclear. A more thorough understanding of the mechanisms that cause translocations will be aided by continuing characterization of translocation breakpoints and by developing in vitro and in vivo model systems that can generate chromosome translocation. J. Cell. Biochem. 102: 320–331, 2007. © 2007 Wiley‐Liss, Inc.