bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma
Authors: D'Arrigo Antonello , Belluco Claudio , Ambrosi Alessandro , Digito Maura , Esposito Giovanni , Bertola Antonella , Fabris Michele , Nofrate Valentina , Mammano Enzo , Leon Alberta , Nitti Donato , Lise Mario 
Published: February 2005

AbstractMetastatic spread to the liver is the major contributor to mortality in patients with colorectal carcinoma (CRC). In order to seek for gene expression patterns associated with metastatic potential in primary CRC, we compared the transcriptional profiles of 10 radically resected primary CRCs from patients who did not develop distant metastases within a 5‐year follow‐up period with those of 10 primary/metastatic tumor pairs from patients with synchronous liver metastases. To focus selectively on neoplastic cells, the study was conducted on laser‐microdissected bioptic tissues. Arrays of 7,864 human cDNAs were utilized. While a striking transcriptional similarity was observed between the primary tumors and their distant metastases, the nonmetastasizing primary tumors were clearly distinct from the primary/metastatic tumor pairs. Of 37 gene expression differences found between the 2 groups of primary tumors, 29 also distinguished nonmetastasizing tumors from metastases. The gene encoding for mannosyl (α‐1,3‐)‐glycoprotein β‐1,4‐N‐acetyl‐glucosaminyl‐transferase (GnT‐IV) became significantly upregulated in primary/metastatic tumor pairs (p < 0.001). GnT‐IV upregulation was confirmed by RT‐PCR. These data support the existence of a specific transcriptional signature distinguishing primary colon adenocarcinomas with different metastatic potential, the further pursuit of which may lead to relevant clinical and therapeutic applications. © 2005 Wiley‐Liss, Inc.
Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4′‐tetramethoxystilbene (DMU‐212) on adenoma development in the ApcMin+ mouse and cyclooxygenase‐2 in human‐derived colon cancer cells
Authors: Sale Stewart , Tunstall Richard G. , Ruparelia Ketan C. , Potter Gerry A. , Steward William P. , Gescher Andreas J. 
Published: February 2005

AbstractNaturally occurring molecules with putative cancer chemopreventive properties such as the phytoalexin resveratrol (3,5,4′‐trihydroxystilbene) are lead molecules that guide the design of novel agents with improved pharmacologic properties. The synthetic resveratrol analog 3,4,5,4′‐tetramethoxystilbene (DMU‐212) has been shown to possess stronger antiproliferative properties in human colon cancer cells than resveratrol. We tested the hypothesis that DMU‐212 is also a more potent inhibitor of adenoma development in the ApcMin+ mouse, a model of human intestinal carcinogenesis. ApcMin+ mice received either stilbene derivative with the diet (0.2%), and adenomas were counted after experiments were terminated. Resveratrol and DMU‐212 decreased adenoma load by 27% and 24%, respectively, compared to untreated controls. Cyclooxygenase (COX) enzymes are important mechanistic targets of resveratrol, and we investigated whether DMU‐212 interferes with the expression and activity of COX in human colon cells. Incubation of HCA‐7 cancer cells for 24–96 hr with either stilbene derivative (1–50 μM) decreased prostaglandin E‐2 (PGE‐2) production, but only resveratrol decreased COX‐2 protein expression. In mice, which received either stilbene derivative (0.2%) for 3 weeks with their diet, PGE‐2 levels in the intestinal mucosa were reduced by between 45% and 62% compared to mice on control diet. While resveratrol inhibited enzyme activity in purified COX preparations, DMU‐212 failed to do so. The PGE‐2 decrease seen with DMU‐212 in cells and in vivo is probably mediated via its metabolites. The results suggest that alteration of the resveratrol molecule to generate DMU‐212 does not abrogate its ability to decrease adenoma number in ApcMin+ mice or to interfere with PGE‐2 generation in cells. © 2005 Wiley‐Liss, Inc.
DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress‐induced apoptosis
Authors: Di Stasi Delia , Vallacchi Viviana , Campi Valentina , Ranzani Tiziana , Daniotti Maria , Chiodini Elena , Fiorentini Silvia , Greeve Isabell , Prinetti Alessandro , Rivoltini Licia , Pierotti Marco A. , Rodolfo Monica 
Published: February 2005

AbstractThe DHCR24 gene encoding for the 3β‐hydroxysterol Δ24‐reductase, an oxidoreductase involved in cholesterol biosynthesis, was isolated by subtractive hybridization as highly expressed in a short‐term melanoma cell line derived from a cutaneous metastases (S/M2) compared to that obtained from the autologous primary tumor (S/P). DHCR24 (alias seladin‐1, diminuto/dwarf1 homolog) has been reported to act as an antiapoptotic factor in neurons. Gene expression analysis by Northern blot confirmed that DHCR24 was 5‐fold upregulated in S/M2 compared to S/P cells. High levels of DHCR24 gene expression were detected in 13/25 melanoma metastases and in 1/7 primary melanomas by real‐time PCR, indicating that upregulation of this gene may occur in melanoma progression. In S/M2 cells, high DHCR24 gene expression associated with resistance to apoptosis triggered by oxidative stress induced by exposure to hydrogen peroxide. DHCR24 gene transfer was shown to protect melanoma cells from H2O2‐induced cytotoxicity. Although higher cholesterol levels were shown in S/M2 cells compared to S/P cells, DHCR24 gene transfer did not increase cholesterol content. To evaluate whether DHCR24 acts as an antiapoptotic factor in melanoma metastases, the cytotoxic effect of chemotherapeutic agents was tested in DHCR24 transfectants and in the presence of a DHCR24 inhibitor, U18666A. High DHCR24 gene expression in transfectants did not result in a higher resistance to cytotoxic agents; treatment with U18666A was cytotoxic in S/P cells with a lower DHCR24 content and showed additive cytotoxic effect only when associated with H2O2 and not with cysplatin or etoposide, indicating that the DHCR24 protective effect is exerted through an oxidative stress‐specific mechanism. © 2005 Wiley‐Liss, Inc.
Risk factors for Kaposi's sarcoma among HHV‐8 seropositive homosexual men with AIDS
Authors: Nawar Eric , Mbulaiteye Sam M. , Gallant Joel E. , Wohl David A. , Ardini Marianne , Hendershot Tabitha , Goedert James J. , Rabkin Charles S. 
Published: February 2005

AbstractKaposi's sarcoma (KS) is a frequent complication of the acquired immunodeficiency syndrome (AIDS) in homosexual men. Risk factors for developing this malignancy are uncertain, other than immunosuppression and coinfection with human herpesvirus 8 (HHV‐8). We therefore examined factors associated with KS in a cross‐sectional analysis of 99 cases among 503 HHV‐8 seropositive homosexual men with AIDS. Data were collected by computer‐assisted personal interviews and medical chart reviews. HHV‐8 seroreactivity was determined by enzyme‐linked immunosorbent assay for antibodies against HHV‐8 K8.1 glycoprotein. KS was significantly less common in blacks compared to whites [risk ratio (RR) = 0.4; 95% CI = 0.2 =0.8] and more common in subjects who had completed college (RR = 1.7; 95% CI = 1.1–2.7) or had annual income greater than $30,000 (RR = 1.5; 95% CI = 1.1–2.2). KS was less common in cigarette smokers (RR = 0.6; 95% CI = 0.5–0.9) and users of crack cocaine (RR = 0.4; 95% CI = 0.1–0.8). KS was less common in bisexual men compared to men who were exclusively homosexual (estimated RR = 0.6; 95% CI = 0.4–0.9) and inversely associated with number of female partners. KS was also less common in men who had received pay for sex (RR = 0.6; 95% CI = 0.4–1.0). These cross‐sectional associations could be biased by potential differences in relative timing of HHV‐8 and HIV infection, a postulated determinant of KS risk. Alternatively, our findings may reflect factors protective against KS in individuals infected with HHV‐8. Future research should focus on identifying practical measures for countering KS that do not increase the risk of other diseases. Published 2005 Wiley‐Liss, Inc.
Suppression of hepatocellular carcinoma by transplantation of ex‐vivo immune‐modulated NKT lymphocytes
Authors: Margalit Maya , Shibolet Oren , Klein Athalia , Elinav Eran , Alper Ruslana , Thalenfeld Barbara , Engelhardt Dean , Rabbani Elazar , Ilan Yaron 
Published: February 2005

AbstractNKT cells are a regulatory subset of T lymphocytes with immune modulatory effects and an important role in anti‐tumor immunity. The feasibility of “ex‐vivo education” of NKT cells has recently been demonstrated. To evaluate the anti‐tumor effect of ex‐vivo immune‐modulated NKT lymphocytes in a murine model of hepatocellular carcinoma. Athymic Balb/C mice were sublethally irradiated and transplanted with human Hep3B HCC. NKT cells prepared from immunocompetent Balb/C mice were pulsed ex vivo with HCC‐derived antigens (Group A), Hep3B cells (group B) or BSA (group C), and adoptively transferred into HCC harboring mice (1 × 06 NKT cells per mouse). Group D mice did not undergo NKT cell transplantation. Group E mice were transplanted with 1 × 106 NKT cells from HBV‐immunized donors. Mice were followed for tumor size and weight. To determine the mechanism of the anti‐tumor effect, intrasplenic lymphocyte populations were analyzed by FACS for NKT, CD4+ and CD8+ lymphocyte subpopulations; STAT 1, 4 and 6 expression in splenocytes was assessed by Western blot, and serum cytokine levels were measured by ELISA. Adoptive transfer of NKT cells pulsed with HCC‐derived antigens (group A) and NKT cells from immunized donors (group E) resulted in complete disappearance of tumors within 4 weeks and attenuated weight loss (6.5% and 7% in groups A and E, respectively). In contrast, mice in groups B, C, and D developed large, necrotic tumors and severe weight loss (21%, 17% and 23% weight loss in groups B, C, and D, respectively). NKT/CD4 and CD8/CD4 ratios were significantly increased in groups A and E (12.3 and 17.6 in groups A and D, respectively, compared to 6.4, 4.8 and 5.6 in groups B, C and D, respectively, for the NKT/CD4 ratio; 41 and 19.8 in groups A and E, respectively, compared to 6.5, 11.8 and 3.2 in groups B, C, and D, respectively, for the CD8/CD4 ratio). Expression of the transcription factor STAT4 was evident in group A, but not in groups B‐D. Serum IFNγ, IL12 and IL4 levels were increased in groups A and E. Adoptive transfer of NKT lymphocytes exposed ex vivo by HCC‐derived antigens loaded on dendritic cells and NKT cells from immunized donors led to suppression of HCC in mice. NKT‐mediated anti‐tumor activity was associated increased NKT and CD8+ T lymphocyte numbers, increased expression of STAT4, a marker for IL‐12 activity and elevated serum levels of the proinflammatory cytokines IFNγ and IL12, and of IL4. Ex‐vivo modulation of NKT lymphocytes holds promise as a novel mode of immune therapy for HCC. © 2005 Wiley‐Liss, Inc.
N‐Acetyltransferase‐2, glutathione S‐transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: A case‐control study
Authors: Gelatti Umberto , Covolo Loredana , Talamini Renato , Tagger Alessandro , Barbone Fabio , Martelli Claudia , Cremaschini Francesca , Franceschi Silvia , Ribero Maria Lisa , Garte Seymour , Nardi Giuseppe , Donadon Valter , Donato Francesco 
Published: February 2005

AbstractOur aim was to evaluate the role of N‐acetyltransferase (NAT2) and glutathione S‐transferase M1 and T1 (GSTM1 and GSTT1) polymorphisms in hepatocellular carcinoma (HCC) according to cigarette smoking, taking into account hepatitis B (HBV) and C (HCV) viral infection as well as alcohol consumption. A hospital‐based case‐control study was conducted in 2 areas of north Italy. Cases (n = 200) were patients hospitalized for HCC, and controls (n = 400) were patients admitted for reasons other than liver disease, neoplasms and tobacco‐ and alcohol‐related diseases. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism–based method. The putative risk genotypes NAT2 slow acetylator, GSTM1 null and GSTT1 null were not associated with HCC (OR = 1.3, 95% CI 0.8–2.0; OR = 1.0, 95% CI 0.6–1.5; OR = 0.8, 95% CI 0.4–1.4, respectively). Although not statistically significant, an increase in HCC risk was observed among light smokers (1–20 pack‐years) carrying GSTT1 null (OR = 1.7, 95% CI 0.6–4.7) and NAT2 slow acetylator (OR = 1.3, 95% CI 0.6–3.0) genotypes. In conclusion, there was no evidence for a gene–environment interaction in HCC risk for GSTM1, GSTT1 and NAT2 genotypes. © 2005 Wiley‐Liss, Inc.
Retracted: The evolution of predictive oncology and molecular‐based therapy for oral cancer prevention
Authors: Sudbø Jon , Reith Albrecht 
Published: February 2005

AbstractRetraction: The following article from International Journal of Cancer, “The evolution of predictive oncology and molecular‐based therapy for oral cancer prevention”, by Jon Sudbø and Albrecht Reith, published online in Wiley InterScience (http://www3.interscience.wiley.com) on 1 February 2005 and in Volume 115, Number 3, pages 339‐345, has been retracted by agreement among the author Albrecht Reith, the journal Editor in Chief, Peter Lichter, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation conducted by the Rikshospitalet‐Radiumhospitalet MC and the University of Oslo into the work carried out by Jon Sudbø.
Cooperative induction of rat mammary cancer by radiation and 1‐methyl‐1‐nitrosourea via the oncogenic pathways involving c‐Myc activation and H‐ras mutation
Authors: Imaoka Tatsuhiko , Nishimura Mayumi , Teramoto Ayako , Nishimura Yukiko , Ootawara Masami , Osada Harumi , Kakinuma Shizuko , Maekawa Akihiko , Shimada Yoshiya 
Published: February 2005

AbstractHumans are continually exposed to various environmental carcinogens. Cancers may arise as a result of exposure to carcinogenic chemicals, ionizing radiation or a combination thereof. However, the mechanism of combined carcinogenesis has been only deduced from oncogenic actions of individual agents. Here, we analyzed experimental mammary carcinogenesis caused by a combination of radiation and a chemical carcinogen, 1‐methyl‐1‐nitrosourea (MNU). Seven‐week‐old female Sprague‐Dawley rats were divided into 4 groups: control, gγ‐irradiated (2 Gy), MNU‐treated (40 mg/kg, i.p.) and combined treatment of radiation with subsequent MNU after 3 days. Rats with palpable tumors were sacrificed at 50 weeks of age to collect tumors for histologic typing and mutational analysis of the H‐ras gene codon 12. The combined treatment induced adenocarcinomas, but not fibroadenomas, more efficiently than radiation or MNU alone. The H‐ras mutation was not seen in radiation‐induced carcinomas and was specific to MNU‐induced carcinomas in individually treated groups. In the combined treatment group, H‐ras‐mutated, but not nonmutated, tumors were more frequent and developed significantly earlier than in the MNU‐treated group. Significantly higher numbers of cells were stained for activated c‐Myc protein in gγ‐ray‐ and combined treatment‐induced cancers than in MNU‐induced cancers. These results indicate that combined exposure to the 2 carcinogens elicits an unexpected cooperativity in which pre‐irradiation enhances mammary carcinogenesis predominantly through the oncogenic pathway involving H‐ras, possibly by synergism with c‐Myc activation. © 2005 Wiley‐Liss, Inc.
Heuristic molecular lipophilicity potential (HMLP): A 2D‐QSAR study to LADH of molecular family pyrazole and derivatives
Authors: Du Qishi , Mezey P. G. , Chou Kuo‐Chen 
Published: February 2005

AbstractThe quantum chemical and structure‐based technique heuristic molecular lipophilicity potential (HMLP) is used in the liver alcohol dehydrogenase (LADH) study of molecular family pyrazole and derivatives. The molecular lipophilic index LM, molecular hydrophilic index HM, lipophilic indices lss, and hydrophilic indices hss of the substitutes (fragments), and atomic lipophilicity indices las are constructed and used in QSAR study. The HMLP indices are correlated with bioactivities of 18 pyrazole derivatives according to the 2D QSAR procedure. The multiple linear regression equation between the bioactivities of pyrazole derivatives and HMLP indices are built using partial least square (PLS) with the optimal statistical quantity (r = 0.987, s = 0.479, F = 47.19). The inhibition mechanism of LADH of the pyrazole derivatives is explained according to the physical meaning of HMLP indices. During the HMLP calculations for the 2D QSAR, the only input parameters are the atomic van der Waals radius without the need to resort to any empirical parameters. Accordingly, HMLP can provide a rigorous theoretical approach with a crystal clear physical meaning for the 2D QSAR. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 461–470, 2005
Maximal probability domains in linear molecules
Authors: Gallegos A. , Carbó‐Dorca R. , Lodier F. , Cancès E. , Savin A. 
Published: February 2005

AbstractRegions of space are defined to maximize the probability to find a given number of electrons within. Their chemical significance and their relationship to the electron localization function (ELF) are explored by analyzing the results for a few linear molecules: LiH, BH, N2, CO, CS, C2H2, and C4H2. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 455–460, 2005
Myotubularin phosphoinositide phosphatases, protein phosphatases, and kinases: Their roles in junction dynamics and spermatogenesis
Authors: Zhang Jiayi , Mruk Dolores D. , Cheng C. Yan 
Published: February 2005

AbstractSpermatogenesis in the seminiferous epithelium of the mammalian testis is a dynamic cellular event. It involves extensive restructuring at the Sertoli–germ cell interface, permitting germ cells to traverse the epithelium from basal to adluminal compartment. As such, Sertoli–germ cell actin‐based adherens junctions (AJ), such as ectoplasmic specializations (ES), must disassemble and reassemble to facilitate this event. Recent studies have shown that AJ dynamics are regulated by intricate interactions between AJ integral membrane proteins (e.g., cadherins, α6β1 integrins and nectins), phosphatases, kinases, adaptors, and the underlying cytoskeleton network. For instance, the myotubularin (MTM) phosphoinositide (PI) phosphatases, such as MTM related protein 2 (MTMR2), can form a functional complex with c‐Src (a non‐receptor protein tyrosine kinase). In turn, this phosphatase/kinase complex associates with β‐catenin, a constituent of the N‐cadherin/β‐catenin functional unit at the AJ site. This MTMR2‐c‐Src‐β‐catenin complex apparently regulates the phosphorylation status of β‐catenin, which determines cell adhesive function conferred by the cadherin–catenin protein complex in the seminiferous epithelium. In this review, we discuss the current status of research on selected phosphatases and kinases, and how these proteins potentially interact with adaptors at AJ in the seminiferous epithelium to regulate cell adhesion in the testis. Specific research areas that are open for further investigation are also highlighted. © 2005 Wiley‐Liss, Inc.
Microwave‐Assisted Direct Synthesis and Polymerization of Chiral Acrylamide
Authors: Iannelli Mauro , Ritter Helmut 
Published: February 2005

AbstractSummary: Chiral (R)‐N‐(1‐phenylethyl)‐acrylamide (3) was synthesized directly from acrylic acid (1) and (R)‐1‐phenylethylamine (2) via microwave irradiation without any further activation and in a solvent‐free medium. The kinetic measurements performed show high selectivity and conversion to the amide after only few minutes of reaction time. It was possible to obtain optically active polymers containing both acrylamide and imide structural units in a one‐pot reaction starting from acrylic acid (1), amine (2) and AIBN as a free radical initiator. The same reactions were evaluated by classical thermal heating in an oil bath and the results are compared.The condensation reaction between acrylic acid and (R)‐1‐phenylethylamine by MW irradiation in the presence and absence of AIBN as a free radical initiator.magnified imageThe condensation reaction between acrylic acid and (R)‐1‐phenylethylamine by MW irradiation in the presence and absence of AIBN as a free radical initiator.
Evidence for the presence of α1 adrenoceptor subtypes in the human ureter
Authors: Sigala Sandra , Dellabella Marco , Milanese Giulio , Fornari Sara , Faccoli Stefania , Palazzolo Francesca , Peroni Angelo , Mirabella Giuseppe , Cunico Sergio Cosciani , Spano PierFranco , Muzzonigro Giovanni 
Published: February 2005

AbstractAimSeveral studies have proposed a role for α1 adrenoceptors (ARs) in ureteral physiology, indicating that they are present in the ureter; however, few studies have been done to identify α1 AR subtypes present in this area. Thus, this study was carried out to characterize the α1 AR subtype gene and protein expression in proximal, medial, and distal region of the human ureter.MethodsMolecular characterization of α1 AR subtypes were analyzed by semi‐quantitative RT‐PCR. α1 AR protein expression was studied by saturation binding curves and by competition binding curves with selective antagonists. Analysis of data was performed using the GraphPad PRISM 4 software.ResultsAnalysis of saturation binding curves revealed a heterogeneous distribution of α1 AR binding sites, the Bmax for the distal ureter was indeed 52.5 ± 5.4 fmol/mg prot, while a lower similar density of α1 ARs was demonstrated in the medial (25.2 ± 1.7 fmol/mg prot) and proximal (23.4 ± 0.4 fmol/mg prot) ureters. Molecular and pharmacological characterization of α1 AR subtypes indicated that each receptor was present, although with differences in terms of the amount expressed.ConclusionsHuman ureter was endowed with each α1 AR subtype, although α1D and α1A ARs were prevalent over α1B ARs. Radioligand binding results revealed that there were no significant differences in the Kd between ureteral regions, while a heterogeneous distribution of α1 AR binding sites was detected, with the highest density of α1 ARs in the distal ureter and a lower similar density in the medial and proximal ureters. Neurourol. Urodynam. 24:142–148, 2005. © 2005 Wiley‐Liss, Inc.
Smooth muscle membrane organization in the normal and dysfunctional human urinary bladder: A structural analysis
Authors: Burkhard Fiona C. , Monastyrskaya Katia , Studer Urs E. , Draeger Annette 
Published: February 2005

AbstractPurposeThe decline in contractile properties is a characteristic feature of the dysfunctional bladder as a result of infravesical outlet obstruction. During clinical progression of the disease, smooth muscle cells undergo structural modifications. Since adaptations to constant changes in length require a high degree of structural organization within the sarcolemma, we have investigated the expression of several proteins, which are involved in smooth muscle membrane organization, in specimens derived from normal and dysfunctional organs.Materials and MethodsSpecimen from patients with urodynamically normal/equivocal (n = 4), obstructed (n = 2), and acontractile (n = 2) bladders were analyzed relative to their structural features and sarcolemmal protein profile.ResultsSmooth muscle cells within the normal urinary bladder display a distinct sarcolemmal domain structure, characterized by firm actin‐attachment sites, alternating with flexible “hinge” regions. In obstructed bladders, foci of cells displaying degenerative sarcolemmal changes alternate with areas of hypertrophic cells in which the membrane appears unaffected. In acontractile organs, the overall membrane structure remains intact, however annexin 6, a protein belonging to a family of Ca2+‐dependent, “membrane‐organizers,” is downregulated.ConclusionDegenerative changes in smooth muscle cells, which are chronically working against high resistance, are preferentially located within the actin‐attachment sites. In acontractile bladders, the downregulation of annexin 6 might have a bearing on the fine‐tuning of the plasma membrane during contraction/relaxation cycles. Neurourol. Urodynam. 24:128–135, 2005. © 2005 Wiley‐Liss, Inc.