bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Human 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

Tumor 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

S‐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

In 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

Family 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

Osteonectin 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

Adult 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

Using 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

While 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

The 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

The 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

In 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

This 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

Cancer 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.
Methylglyoxal and high glucose co‐treatment induces apoptosis or necrosis in human umbilical vein endothelial cells
Authors: Chan Wen‐Hsiung , Wu Hsin‐Jung
Published: August 2007

Hyperglycemia and elevation of methylglyoxal (MG) are symptoms of diabetes mellitus (DM). We previously showed that high glucose (HG; 30 mM) or MG (50–400 µM) could induce apoptosis in mammalian cells, but these doses are higher than the physiological concentrations of glucose and MG in the plasma of DM patients. The physiological concentration of MG and glucose in the normal blood circulation is about 1 µM and 5 mM, respectively. Here, we show that co‐treatment with concentrations of MG and glucose comparable to those seen in the blood circulation of DM patients (5 µM and 15–30 mM, respectively) could cause cell apoptosis or necrosis in human umbilical vein endothelial cells (HUVECs) in vitro. HG/MG co‐treatment directly increased the reactive oxygen species (ROS) content in HUVECs, leading to increases in intracellular ATP levels, which can control cell death through apoptosis or necrosis. Co‐treatment of HUVECs with 5 µM MG and 20 mM glucose significantly increased cytoplasmic free calcium levels, activation of nitric oxide synthase (NOS), caspase‐3 and ‐9, cytochrome c release, and apoptotic cell death. In contrast, these apoptotic biochemical changes were not detected in HUVECs treated with 5 µM MG and 30 mM glucose, which appeared to undergo necrosis. Pretreatment with nitric oxide (NO) scavengers could inhibit 5 µM MG/20 mM glucose‐induced cytochrome c release, decrease activation of caspase‐9 and caspase‐3, and increase the gene expression and protein levels of p53 and p21, which are known to be involved in apoptotic signaling. Inhibition of p53 protein expression using small interfering RNA (siRNA) blocked the activation of p21 and the cell apoptosis induced by 5 µM MG/20 mM glucose. In contrast, inhibition of p21 protein expression by siRNA prevented apoptosis in HUVECs but had no effect on p53 expression. These results collectively suggest that the treatment dosage of MG and glucose could determine the mode of cell death (apoptosis vs. necrosis) in HUVECs, and both ROS and NO played important roles in MG/HG‐induced apoptosis of these cells. J. Cell. Biochem. 103: 1144–1157, 2008. © 2007 Wiley‐Liss, Inc.
S100A6 (calcyclin) enhances the sensitivity to apoptosis via the upregulation of caspase‐3 activity in Hep3B cells
Authors: Joo Joung Hyuck , Yoon Sun Young , Kim Joo Heon , Paik Sang‐Gi , Min Sung Ran , Lim Jong‐Seok , Choe In Seong , Choi Inpyo , Kim Jae Wha
Published: August 2007

S100A6 (calcyclin) is a small calcium‐binding protein which has been implicated in several cellular processes such as cell cycle progression, cytoskeleton rearrangement, and exocytosis. Also the upregulation of S100A6 has been reported in a variety of tumors and linked to metastasis. However, exact intracellular roles of S100A6 related with apoptosis have not been clarified yet. Here we demonstrated that the upregulation of S100A6 enhances the cell death rate compared to the control under the apoptotic conditions. In exogenously S100A6 induced Hep3B cells, cell viability was significantly decreased compared with mock and S100A6‐knockdown cells under calcium ionophore A23187 treatment. The exogenously introduced S100A6 significantly affected the caspase‐3‐like activity in programmed cell death through the enhanced caspase‐3 expression, which was verified by promoter assay in wild or mutant S100A6‐transfected Hep3B cells. Next, the promoter activity of caspase‐3 was increased by 2.5‐folds in wild‐type S100A6‐transfected cells compared to mutant 2 (E67K, mutant of EF‐hand motif) or control. Our results suggest that S100A6 might be involved in the processing of apoptosis by modulating the transcriptional regulation of caspase‐3. J. Cell. Biochem. 103: 1183–1197, 2008. © 2007 Wiley‐Liss, Inc.
Purα as a cellular co‐factor of Rev/RRE‐mediated expression of HIV‐1 intron‐containing mRNA
Authors: Kaminski Rafal , Darbinian Nune , Sawaya Bassel E. , Slonina Dorota , Amini Shohreh , Johnson Edward M. , Rappaport Jay , Khalili Kamel , Darbinyan Armine
Published: August 2007

To ensure successful replication, HIV‐1 has developed a Rev‐mediated RNA transport system that promotes the export of unspliced genomic RNA from nuclei to cytoplasm. This process requires the Rev responsive element (RRE) that is positioned in the viral transcript encoding Env protein, as well as in unspliced and singly spliced viral transcripts. We identified Purα, a single‐stranded nucleic acid binding protein as a cellular partner for Rev that augments the appearance of unspliced viral RNAs in the cytoplasm. A decrease in the level of Purα expression by siRNA diminishes the level of Rev‐dependent expression of viral RNA. Through its nucleic acid binding domain, Purα exhibits the ability to interact with the multimerization and RBD domains of Rev. Similar to Rev, Purα associates with RRE and in the presence of Rev forms a complex with slower electrophoretic mobility than those from Rev:RRE and Purα:RRE. The interaction of Purα with RRE occurs in the cytoplasm where enhanced association of Rev with RRE is observed. Our data indicate that the partnership of Purα with Rev is beneficial for Rev‐mediated expression of the HIV‐1 genome. J. Cell. Biochem. 103: 1231–1245, 2008. © 2007 Wiley‐Liss, Inc.
All in the family: Using inherited cancer syndromes to understand de‐regulated cell signaling in brain tumors
Authors: Houshmandi S. Sean , Gutmann David H.
Published: August 2007

The cell signaling pathways that are tightly regulated during development are often co‐opted by cancer cells to allow them to escape from the constraints that normally limit cell growth and cell movement. In this regard, de‐regulated signaling in cancer cells confers a number of key tumor‐associated properties, including increased cell proliferation, decreased cell death, and increased cell motility. The identification of some of these critical signaling pathways in the nervous system has come from studies of inherited cancer syndromes in which affected individuals develop brain tumors. The study of brain tumors arising in patients with neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and tuberous sclerosis complex (TSC) has already uncovered several key intracellular signaling pathways important for modulating brain tumor growth. An in‐depth analysis of these intracellular signaling pathways will not only lead to an improved understanding of the process of brain tumorigenesis, but may also provide important molecular targets for future therapeutic drug design. J. Cell. Biochem. 102: 811–819, 2007. © 2007 Wiley‐Liss, Inc.
Osteopontin overexpression in breast cancer: Knowledge gained and possible implications for clinical management
Authors: Tuck Alan B. , Chambers Ann F. , Allan Alison L.
Published: August 2007

Osteopontin (OPN) is a secreted protein that is overexpressed in a number of human cancers, and has been associated with increased metastatic burden and poor prognosis in breast cancer patients. The OPN protein contains several conserved structural elements including heparin‐ and calcium‐binding domains, a thrombin‐cleavage site, a CD44 binding site, and two integrin‐binding sites. Experimental studies have shown that the ability of OPN to interact with a diverse range of factors, including cell surface receptors (integrins, CD44), secreted proteases (matrix metalloproteinases, urokinase plasminogen activator), and growth factor/receptor pathways (TGFα/EGFR, HGF/Met) is central to its role in malignancy. These complex signaling interactions can result in changes in gene expression, which ultimately lead to alterations in cell properties involved in malignancy such as adhesion, migration, invasion, enhanced tumor cell survival, tumor angiogenesis, and metastasis. Therefore, OPN is not merely associated with cancer, but rather it plays a multi‐faceted functional role via complex molecular cross‐talk with other factors. This review will focus on the role of OPN in breast cancer, in particular on the malignancy‐promoting aspects of OPN that may reveal opportunities for new approaches to the clinical management of breast cancer. J. Cell. Biochem. 102: 859–868, 2007. © 2007 Wiley‐Liss, Inc.
Overexpression of Akt1 upregulates glycogen synthase activity and phosphorylation of mTOR in IRS‐1 knockdown HepG2 cells
Authors: Varma Shailly , Khandelwal Ramji L.
Published: August 2007

Insulin receptor substrate (IRS) proteins are important docking proteins in mediating the insulin signaling cascade. We have investigated the effect of short interfering RNA (siRNA) mediated knockdown of IRS‐1 on insulin signaling cascade in primary human hepatocellular carcinoma HepG2 cell line and HepG2 cells overexpressing Akt1/PKB‐α (HepG2‐CA‐Akt/PKB). IRS‐1 knockdown in both cell lines resulted in reduction of insulin stimulated Akt1 phosphorylation at Ser 473. In parental HepG2 cells, IRS‐1 knockdown resulted in reduction (ca. 50%) in the basal level of phosphorylated mTOR (Ser 2448) irrespective of insulin treatment. In contrast, HepG2‐CA‐Akt/PKB cells showed an upregulation in the basal level of phosphorylated mTOR (Ser 2448) (ca. 40%). Insulin mediated phosphorylation of mTOR was reduced. IRS‐1 knockdown also reduced the cell proliferation of parental HepG2 cells by ca. 30% in the presence/absence of insulin, whereas in HepG2‐CA‐Akt/PKB the cell proliferation was reduced by 15% and treatment of insulin further reduced it to ca. 50% (vs. control). IRS‐1 knockdown also reduced the glycogen synthase (GS) activity in parental HepG2 cells, however, it was upregulated in HepG2‐CA‐Akt/PKB cells.

These results suggest that knockdown of IRS‐1 abolished basal as well as insulin mediated phosphorylation/activity of proteins involved in cell proliferation or glycogen metabolism in the parental Hep2 cells. IRS‐1 knockdown in cells overexpressing constitutively active Akt1/PKB‐α either did not change or upregulated the basal levels of phosphorylated/active proteins. However, insulin mediated response was either not altered or downregulated in these cells. J. Cell. Biochem. 103: 1424–1437, 2008. © 2007 Wiley‐Liss, Inc.
Systematic studies on the computation of nuclear magnetic resonance shielding constants and chemical shifts: The density functional models
Authors: Wu Anan , Zhang Ying , Xu Xin , Yan Yijing
Published: August 2007

We present a systematic density functional investigation on the prediction of the 13C, 15N, 17O, and 19F NMR properties of 23 molecules with 21 density functionals. Extensive comparisons are made for both 13C magnetic shieldings and chemical shifts with respect to the gas phase experimental data and the best CCSD(T) results. We find that the OPBE and OPW91 exchange‐correlation functionals perform significantly better than some popular functionals such as B3LYP and PBE1PBE, even surpassing, in many cases, the standard wavefunction‐based method MP2. Further analysis has been performed to explore the individual role played by various exchange and correlation functionals. We find that the B88 and PBE exchange functionals have a too strong tendency of deshielding, leading to too deshielded magnetic shielding constants; whereas the OPTX exchange functional performs remarkably well. We claim that the main source of error arises from the exchange functional, but correlation functional also makes important contribution. We find that the correlation functionals may be grouped into two classes. class A, such as LYP and B98, leads to deshielded NMR values, deteriorating the overall performance; whereas class B, such as PW91 and PBE, generally increases the absolute shieldings, which complements the exchange functionals, leading to improved results in the calculation of NMR data. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Excited states of GFP chromophore and active site studied by the SAC‐CI method: Effect of protein‐environment and mutations
Authors: Hasegawa Jun‐Ya , Fujimoto Kazuhiro , Swerts Ben , Miyahara Tomoo , Nakatsuji Hiroshi
Published: August 2007

Excited states of fluorescent proteins were studied using symmetry‐adapted cluster‐configuration interaction (SAC‐CI) method. Protein‐environmental effect on the excitation and fluorescence energies was investigated. In green fluorescent protein (GFP), the overall protein‐environmental effect on the first excitation energy is not significant. However, glutamine (Glu) 94 and arginine (Arg96) have the red‐shift contribution as reported in a previous study (Laino et al., Chem Phys 2004, 298, 17). The excited states of GFP active site (GFP‐W22‐Ser205‐Glu222‐Ser65) were also calculated. Such large‐scale SAC‐CI calculations were performed with an improved code containing a new algorithm for the perturbation selection. The SAC‐CI results indicate that a charge‐transfer state locates at 4.19 eV, which could be related to the channel of the photochemistry as indicated in a previous experimental study. We also studied the excitation and fluorescence energies of blue fluorescent protein, cyan fluorescent protein, and Y66F. The SAC‐CI results are very close to the experimental ones. The protonation state of blue fluorescent protein was determined. Conformation of cyan fluorescent protein indicated by the present calculation agrees to the experimentally observed structure. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Theoretical investigation on the protonation reactions and products of the stable [N,C,C,S] isomers
Authors: Kan Wei , Yu Hai‐Tao , Fu Hong‐Gang , Wu Yi‐Qun
Published: August 2007

A theoretical study on the protonation system of [N,C,C,S], [H,N,C,C,S]+, was performed at the B3LYP/6‐311++G(d,p) and CCSD(T)/6‐311++G(2df,2p) (single point) levels of theory. On the doublet [H,N,C,C,S]+ surface, 24 species were located as energy minima and 10 of them were considered as kinetically stable species. The species HNCCS+ with 2A′ state and a shallow W‐shaped skeleton was predicted to be the global minimum and kinetically the most stable species, being in good agreement with previous experimental findings. Furthermore, the protonation reactions of the stable [N,C,C,S] isomers were investigated in detail. The calculation results indicated that the [N,C,C,S] isomers may be significantly stabilized upon protonation. Finally, the possible covalent structures of the [H,N,C,C,S]+ isomers with considerable stability were briefly discussed. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
IDEA: Interface dynamics and energetics algorithm
Authors: Duca D. , Barone G. , Giuffrida S. , Varga Zs.
Published: August 2007

IDEA, interface dynamics and energetics algorithm, was implemented, in FORTRAN, under different operating systems to mimic dynamics and energetics of elementary events involved in interfacial processes. The code included a parallel elaboration scheme in which both the stochastic and the deterministic components, involved in the developed physical model, worked simultaneously. IDEA also embodied an optionally running VISUAL subroutine, showing the dynamic energy changes caused by the surface events, e.g., occurring at the gas‐solid interface. Monte Carlo and ordinary differential equation system subroutines were employed in a synergistic way to drive the occurrence of the elementary events and to manage the implied energy flows, respectively. Biphase processes, namely isothermal and isobaric adsorption of carbon monoxide on nickel, palladium, and platinum surfaces, were first studied to test the capability of the code in modeling real frames. On the whole, the simulated results showed that IDEA could reproduce the inner characteristics of the studied systems and predict properties not yet experimentally investigated. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water
Authors: Gao Jiali , Wong Kin‐Yiu , Major Dan T.
Published: August 2007

An integrated Feynman path integral‐free energy perturbation and umbrella sampling (PI‐FEP/UM) method has been used to investigate the kinetic isotope effects (KIEs) in the proton transfer reaction between nitroethane and acetate ion in water. In the present study, both nuclear and electronic quantum effects are explicitly treated for the reacting system. The nuclear quantum effects are represented by bisection sampling centroid path integral simulations, while the potential energy surface is described by a combined quantum mechanical and molecular mechanical (QM/MM) potential. The accuracy essential for computing KIEs is achieved by a FEP technique that transforms the mass of a light isotope into a heavy one, which is equivalent to the perturbation of the coordinates for the path integral quasiparticle in the bisection sampling scheme. The PI‐FEP/UM method is applied to the proton abstraction of nitroethane by acetate ion in water through molecular dynamics simulations. The rule of the geometric mean and the Swain–Schaad exponents for various isotopic substitutions at the primary and secondary sites have been examined. The computed total deuterium KIEs are in accord with experiments. It is found that the mixed isotopic Swain–Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Full configuration interaction calculation of the low lying valence and Rydberg states of BeH
Authors: Pitarch‐Ruiz J. , Sánchez‐Marín J. , Velasco A. M.
Published: August 2007

The all‐electron full configuration interaction (FCI) vertical excitation energies for some low lying valence and Rydberg excited states of BeH are presented in this article. A basis set of valence atomic natural orbitals has been augmented with a series of Rydberg orbitals that have been generated as centered onto the Be atom. The resulting basis set can be described as 4s2p1d/2s1p (Be/H) + 4s4p3d. It allows to calculate Rydberg states up to n= {3,4,5} of the s, p, and d series of Rydberg states. The FCI vertical ionization potential for the same basis set and geometry amounts to 8.298 eV. Other properties such as FCI electric dipole and quadrupole moments and FCI transition dipole and quadrupole moments have also been calculated. The results provide a set of benchmark values for energies, wave functions, properties, and transition properties for the five electron BeH molecule. Most of the states have large multiconfigurational character in spite of their essentially single excited nature and a number of them present an important Rydberg‐valence mixing that is achieved through the mixed nature of the particle MO of the single excitations. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Components for integral evaluation in quantum chemistry
Authors: Kenny Joseph P. , Janssen Curtis L. , Valeev Edward F. , Windus Theresa L.
Published: August 2007

Sharing low‐level functionality between software packages enables more rapid development of new capabilities and reduces the duplication of work among development groups. Using the component approach advocated by the Common Component Architecture Forum, we have designed a flexible interface for sharing integrals between quantum chemistry codes. Implementation of these interfaces has been undertaken within the Massively Parallel Quantum Chemistry package, exposing both the IntV3 and Cints/Libint integrals packages to component applications. Benchmark timings for Hartree‐Fock calculations demonstrate that the overhead due to the added interface code varies significantly, from less than 1% for small molecules with large basis sets to nearly 10% for larger molecules with smaller basis sets. Correlated calculations and density functional approaches encounter less severe performance overheads of less than 5%. While these overheads are acceptable, additional performance losses occur when arbitrary implementation details, such as integral ordering within buffers, must be handled. Integral reordering is observed to add an additional overhead as large as 12%; hence, a common standard for such implementation details is desired for optimal performance. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Understanding topological symmetry: A heuristic approach to its determination
Authors: Contreras M. L. , Alvarez J. , Guajardo D. , Rozas R.
Published: August 2007

An algorithm based on heuristic rules for topological symmetry perception of organic structures having heteroatoms, multiple bonds, and any kind of cycle, and configuration, is presented. This algorithm identifies topological symmetry planes and sets of equivalent atoms in the structure, named symmetry atom groups (SAGs). This approach avoids both the need to explore the entire graph automorphism groups, and to encompass cycle determination, resulting in a very effective computer processing. Applications to several structures, some of them highly symmetrical such as dendrimers, are presented. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Excitation and circular dichroism spectra of (−)‐(3aS, 7aS)‐2‐chalcogena‐trans‐hydrindans(Ch = S, Se, Te): SAC and SAC‐CI calculations
Authors: Honda Yasushi , Kurihara Atsushi , Hada Masahiko , Nakatsuji Hiroshi
Published: August 2007

The ground and several electronic excited states of (3aS,7aS)‐2‐chalcogena‐trans‐hydrindans were calculated by the symmetry adapted cluster (SAC) and SAC‐configuration interaction (SAC‐CI) methods. Theoretical electronic excitation spectra and natural circular dichroism (CD) spectra were obtained for these compounds, and the calculated spectra showed good agreement with the experimental ones reported by Laur (Proceedings of the Third International Symposium on Organic Selenium and Tellurium compounds, Metz, France, 1979, pp. 219–299). For all the chalcogen compounds, the first singlet excited states are assigned to n‐σ* and the other states are assigned to n‐Rydberg in our calculations. It indicates that the spectra for the sulfide, selenide, and telluride are almost regarded as the analogues except for the red shifts of the band positions from the sulfide to the telluride. For the telluride, however, the experimental spectra have shapes that cannot be interpreted by the singlet excitations solely. Our calculations predict the triplet states that account for the spectral shapes, indicating importance of the spin‐orbit interaction effects for the accurate reproduction of the experimental spectra of the telluride. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Uterine artery pseudoaneurysm: Unusual cause of delayed postpartum hemorrhage
Authors: Gürses Cemil , Yılmaz Saim , Bıyıklı Sabiha , Yıldız İ. Okan , Sindel Timur
Published: August 2007

We describe a case of uterine artery pseudoaneurysm in a 21‐year‐old woman with postpartum hemorrhage. This condition is easily diagnosed with duplex Doppler sonography and can be treated with embolization, but only if delayed postpartum hemorrhage is considered in the differential diagnosis. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Sonography of chronic Achilles tendinopathy: A case–control study
Authors: Leung John L.Y. , Griffith James F.
Published: August 2007

Purpose

To describe the sonographic appearance of Achilles tendon in normal subjects and patients with chronic Achilles tendinopathy with the aim of establishing diagnostic sonographic criteria for Achilles tendinopathy.

Methods

A prospective, cross‐sectional, case–control sonographic study of the Achilles tendon was undertaken. Thirty tendons in 21 patients and 100 tendons in 50 control subjects were selected. Sonographic assessment included tendon thickness, echogenicity, fibrillar pattern, and presence of calcifications. Power Doppler imaging was used to assess tendon vascularity. Paratendinous structures and plantar fascia were also examined.

Results

Tendinopathic tendons were larger than normal tendons in both cross‐sectional area and antero‐posterior diameter. Hypoechoic areas within the tendon were more commonly seen in patients. Disruption of fibrillar pattern, increase in tendon vascularity, increased Kager's fat pad echogenicity, and paratenon thickening were solely seen in patients. Fluid in the retrocalcaneal bursa and calcaneal bony abnormalities were seen in both groups without a significant difference.

Conclusion

Achilles tendinopathy results in enlargement, particularly of the mid‐ and distal portions of the tendon, disruption of fibrillar pattern, and increase in tendon vascularity. Additional signs are increased Kager's fat pad echogenicity and paratenon thickening. Tendon calcification, changes in retrocalcaneal bursae, and calcaneal contour are not specific for Achilles tendinopathy. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
Ultrastructural modifications of cell membranes induced by “electroporation” on melanoma xenografts
Authors: Spugnini Enrico P. , Arancia Giuseppe , Porrello Alessandro , Colone Marisa , Formisano Giuseppe , Stringaro Annarita , Citro Gennaro , Molinari Agnese
Published: August 2007

Electroporation (EP) has been widely employed in the past years as a safe and effective technique to drive drugs and DNA plasmids into target cells both for experimental and therapeutic purposes. Despite the large bulk of literature on this topic, often describing successful outcomes, there is a lack of knowledge about the intimate mechanism(s) controlling this phenomenon. In this paper, we describe a number of ultrastructural alterations in the cellular membranes following the exposure of orthotopic melanomas and red blood cells to trains of biphasic pulses. Specifically, melanoma xenografts grown in nude mice were subject to trains of eight biphasic pulses using an electric field of 1250 or 2450 V/cm, excised after 5 min and processed for electron microscopy. The freeze‐fracturing analysis of both cell types evidenced defects in the dynamic assembly of lipids and proteins, which generate “areas with rough structure” and intensive clustering of intramembrane proteins. Such modifications could be the hallmarks of lipid and protein alterations, of protein cohesion reduction, and of changes in lipid orientation inside cell membranes, as postulated in several mathematical models applied to electroporation, and warrant further investigations. Microsc. Res. Tech., 2007. © 2007 Wiley‐Liss, Inc.