bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open‐label study of escitalopram (Lexapro®) for the treatment of ‘Depression of Alzheimer's disease’ (dAD)
Authors: Rao V. , Spiro J. R. , Rosenberg P. B. , Lee H. B. , Rosenblatt A. , Lyketsos C. G. 
Published: February 2006

AbstractBackgroundDepression is a frequent neuropsychiatric complication of Alzheimer's Disease.MethodsThis study investigated the safety and effectiveness of escitalopram (LEXAPRO) for depression in AD (dAD) as defined by the NIMH consensus criteria in an 8‐week, open‐label treatment study.ConclusionEscitalopram was efficacious and safe for the treatment of dAD in this study. Larger, controlled studies are warranted to further assess the efficacy for mood and behavioral disturbances in this medically fragile population. Copyright © 2006 John Wiley & Sons, Ltd.
Use of antipsychotic medications among elderly residents in long‐term institutional care: a three‐year follow‐up
Authors: Alanen Hanna‐Mari , Finne‐Soveri Harriet , Noro Anja , Leinonen Esa 
Published: February 2006

AbstractObjectiveTo analyse the use of antipsychotic medications, change over time and associated factors in a three‐year follow‐up among elderly residents in long‐term institutional care.DesignRetrospective study was designed with three identical cross‐sectional samples originating from the same long‐term care facilities, and collected 1 July to 31 December in 2001, 2002 and 2003, in Finland. These were extracted from the Resident Assessment Instrument (RAI) database, based on Minimum Data Set (MDS) assessments.SettingOf the data providers 16 were hospital‐based institutions and 25 residential homes.ParticipantsEach of the data sets included 3662‐3867 resident assessments.ResultsThe prevalence use of one or more antipsychotic decreased from 42% in 2001 to 39% in 2003. The overall confounder‐adjusted decrease in antipsychotic use was not statistically significant. However, the use of antipsychotics decreased among residents who had wandering as a behavioural problem (OR 0.79, 95% CI 0.63–0.99) and increased among residents with concomitant use of anxiolytic medications (OR 1.23, 95% CI 1.03–1.48).ConclusionsThe use of antipsychotic medications among residents in long‐term institutional care was common and the caring patterns were quite stable during the observation period. Adequate indications may not have been achieved in all cases. More attention should be paid to the appropriate use of antipsychotics in this frail population. Copyright © 2006 John Wiley & Sons, Ltd.
Alcohol advertising and alcohol consumption by adolescents
Authors: Saffer Henry , Dave Dhaval 
Published: February 2006

AbstractThis study investigates the effects of alcohol advertising on adolescent alcohol consumption. The theory of an industry response function and evidence from prior studies indicate the importance of maximizing the variance in advertising measures. Monitoring the Future (MTF) and National Longitudinal Survey of Youth 1997 (NLSY97) data are augmented with alcohol advertising, originating on the market level, for five media. The large sample of the MTF allows estimation of race and gender‐specific models. The longitudinal nature of the NLSY97 allows controls for unobserved heterogeneity with state‐level and individual fixed effects. Price and advertising effects are generally larger for females relative to males. Controls for individual heterogeneity yield larger advertising effects, implying that the MTF results may understate the effects of alcohol advertising. Results from the NLSY97 suggest that a 28% reduction in alcohol advertising would reduce adolescent monthly alcohol participation from 25% to between 24 and 21%. For binge participation, the reduction would be from 12% to between 11 and 8%. The past month price–participation elasticity is estimated at −0.26, consistent with prior studies. The results show that reduction of alcohol advertising can produce a modest decline in adolescent alcohol consumption, though effects may vary by race and gender. Copyright © 2006 John Wiley & Sons, Ltd.
Cystic metastasis from head and neck squamous cell cancer: A distinct disease variant?
Authors: Goldenberg David , Sciubba James , Koch Wayne M. 
Published: February 2006

AbstractBackground.Head and neck squamous cell carcinoma (HNSCC) commonly spreads to regional deep cervical nodes. In most cases, these metastases present as firm, solid masses in the designated lymph node chains. A distinct subset of metastatic nodes present as cystic masses, with most of the volume made up of a liquid center surrounded by a thin solid rim. It has been observed that certain squamous cell carcinoma (SCC) subsites are more likely to produce metastases that are cystic. These sites predominantly include primary tumors of tonsil tissue from Waldeyer's ring. In the past, these cystic cancers often have been erroneously diagnosed as branchiogenic carcinomas, that is, a branchial cleft cyst that has undergone malignant degeneration. Today, most authors have concluded that so‐called branchiogenic carcinomas are actually cystic metastases in the neck probably arising from an oropharyngeal primary SCC. The purpose of this work is to consider the phenomenon of cystic lymph node metastasis in head and neck cancer in depth.Methods.A review of the relevant English‐language literature linking cystic metastasis and head and neck cancer was performed.Results.These studies indicate that lateral cystic masses in adults often represent an occult primary cancer originating in the epithelium within Waldeyer's ring.Conclusions.Adult patients who are initially seen with a lateral cystic neck mass must be presumed to have a cancer until proven otherwise. The mass should be biopsied by fine‐needle aspiration (FNA). However, negative FNA findings may be misleading; therefore, an excisional biopsy and examination under anesthesia with directed biopsies of Waldeyer's ring and bilateral tonsillectomy should be considered a part of the diagnostic workup. © 2006 Wiley Periodicals, Inc. Head Neck, 2006
Clinical curiosity: Cribriform‐morular variant of papillary thyroid carcinoma
Authors: Dalal Kimberly M. , Moraitis Dimitrios , Iwamoto Carlos , Shaha Ashok R. , Patel Snehal G. , Ghossein Ronald A. 
Published: February 2006

AbstractBackground.There is an increasing awareness of the association of papillary thyroid carcinoma and familial adenomatous polyposis (FAP). Although the incidence is rare, most tend to occur in women. Several authors have described a distinctive histologic variant of papillary thyroid carcinoma, the cribriform‐morular variant, which is associated with FAP but also may be encountered in patients with non‐FAP. This diagnosis may precede the symptoms of colorectal polyposis.Methods.A healthy 36‐year‐old woman was seen with a left thyroid nodule, and a 34‐year‐old woman with FAP was seen with a right thyroid nodule; both masses were suspicious for papillary thyroid carcinoma. Both patients underwent total thyroidectomy.Results.Pathologic examination of both specimens revealed papillary thyroid carcinoma, cribriform‐morular variant. The first patient subsequently underwent colonoscopy, which was negative for polyposis.Conclusions.Patients diagnosed with the cribriform‐morular variant of papillary thyroid cancer should be screened for the presence of FAP. © 2006 Wiley Periodicals, Inc. Head Neck 28: 471–476, 2006
Smoking is associated with a decrease of O6‐alkylguanine‐DNA alkyltransferase activity in bronchial epithelial cells
Authors: Povey Andrew C. , O'Donnell Paul , Barber Phil , Watson Mandy , Margison Geoffrey P. , Koref Mauro F. Santibáñez 
Published: February 2006

AbstractO6‐alkylguanine‐DNA alkyltransferase (MGMT) represents the first line of defense against the toxic, mutagenic and carcinogenic effects of O6‐alkylguanine adducts in DNA. These adducts mediate the biological activity from a series of alkylating agents, such as the tobacco‐specific nitrosamines, believed to contribute to the carcinogenicity of tobacco smoke. There have been conflicting reports on the effects of smoking on MGMT activity in lung and other tissues. Here, we investigate MGMT activity in peripheral blood mononuclear cells (PBMC) and lung bronchial epithelial cells (BEC), extracted by lung brushings, from smokers and nonsmokers attending a bronchoscopy clinic. MGMT activity was significantly lower in BECs (geometric mean; 95% confidence interval 1.02; 0.86–1.20 fmol/μg DNA) than in PBMCs (7.86; 6.70–9.59 fmol/μg DNA; p < 0.001), suggesting that bronchial epithelia may be particularly sensitive to alkylation damage. More importantly our results indicate that activity in BECs is significantly decreased in samples from current smokers (0.71; 0.54–0.93 fmol/μg DNA) compared to nonsmokers (1.25; 1.03–1.51 fmol/μg DNA; p = 0.002). This could represent an important contribution to the carcinogenicity of tobacco smoke. © 2006 Wiley‐Liss, Inc.
Analysis of fumarate hydratase mutations in a population‐based series of early onset uterine leiomyosarcoma patients
Authors: Ylisaukko‐oja Sanna K. , Kiuru Maija , Lehtonen Heli J. , Lehtonen Rainer , Pukkala Eero , Arola Johanna , Launonen Virpi , Aaltonen Lauri A. 
Published: February 2006

AbstractGermline mutations in fumarate hydratase (FH) gene at 1q43 predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. In HLRCC, the most common clinical features are leiomyomas of the skin and uterus, and in a subset of the families, renal cell cancer (RCC) and uterine leiomyosarcoma (ULMS) occur frequently at young age. This study was conducted to evaluate the possible contribution of FH mutations in a population‐based series of early onset (≤45 years) ULMSs. Eighty‐one cases were identified through the national cancer registry, and samples from 67 cases (83%) were available for FH mutation screening and analysis of allelic imbalance (AI) at the FH locus. Seventeen percent of tumors showed AI. In the mutation analysis, a novel missense mutation K424R was found. The mutation was also found from the patient's normal tissue. To study whether this variant has functional consequences, FH enzyme activity assay was performed in a cell model. The activity of the mutated protein was significantly reduced as compared to wild type (p = 0.009). This study shows that FH germline mutations can occur in seemingly nonsyndromic cases of ULMS (1/67, 1.5%). It appears that on the population level hereditary FH defects do play a role in pathogenesis of sporadic early onset ULMSs, albeit rarely. © 2006 Wiley‐Liss, Inc.
Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV+ nasopharyngeal carcinoma xenografts in SCID mice
Authors: Lacy Jill , Loomis Regina , Grill Susan , Srimatkandada Pavani , Carbone Rocco , Cheng Yung‐Chi 
Published: February 2006

AbstractNasopharyngeal carcinoma (NPC) is causally linked to Epstein‐Barr virus (EBV), and the EBV oncoprotein, latent membrane protein 1 (LMP‐1), is expressed in the majority of NPCs. LMP‐1 upregulates antiapoptotic genes, including bcl‐2, and Bcl‐2 protein is overexpressed in NPC. Given the antiapoptotic and chemoprotective effects of Bcl‐2, it represents a rational therapeutic target in NPC. We have investigated the antitumor and chemosensitizing effects of the Bcl‐2 antisense oligodeoxynucleotide G3139 (oblimersen, Genasense) in NPC. For these studies, we used the C666‐1 line, a stably infected NPC‐derived line that co‐expresses LMP‐1 and Bcl‐2. We have shown that G3139 treatment of C666‐1 in vitro caused sequence‐dependent suppression of Bcl‐2 protein, inhibition of cell growth and enhanced sensitivity to cisplatin (CDDP), as measured by increased antiproliferative and apoptotic effects. In vivo, G3139 treatment (25 mg/kg every 3 days × 5 doses) delayed engraftment and significantly inhibited growth of established C666‐1 xenografts in SCID mice compared to control oligo‐treated animals. However, G3139 alone did not prevent engraftment or cure established tumors in any animals. In contrast, G3139 treatment (25 mg/kg every 3 days × 5 starting on day 7) in combination with CDDP (8 mg/kg on day 14) completely abrogated tumor engraftment in 80% of animals compared to CDDP (0%) or CDDP + control oligo (0%). When treatment was delayed until tumor was established, G3139 in combination with CDDP significantly inhibited tumor growth compared to CDDP or CDDP + control oligo, and cured 69% animals with established tumors. No animals treated with G3139, CDDP or CDDP + control oligo were cured. Tumor burden and response to treatment correlated with EBV DNA load in serum, measured by real‐time PCR. Western blots of tumor extracts obtained during oligo treatment showed that Bcl‐2 levels were significantly decreased in G3139‐treated animals. Our studies have demonstrated that the Bcl‐2 antisense oligodeoxynucleotide, G3139, has proapoptotic effects in C666‐1, and in combination with CDDP, is curative in C666‐1 NPC xenograft tumors in vivo. The sequence‐dependency of these effects is consistent with an antisense mechanism. These studies suggest that Bcl‐2 may represent a biologically relevant target for the development of novel combinatorial therapies for NPC. © 2006 Wiley‐Liss, Inc.
Rapid induction of apoptosis in B‐cell lymphoma by functionally isolated human antibodies
Authors: Fransson Johan , Tornberg Ulla‐Carin , Borrebaeck Carl A.K. , Carlsson Roland , Frendéus Björn 
Published: February 2006

AbstractNovel panning and screening methodology was devised to isolate high affinity human recombinant scFv antibody fragments with functionally associated properties in B lymphoma cells. The approach was used to generate a panel of apoptosis‐inducing antibodies specific for antigens differentially expressed in B lymphoma vs. T leukaemia cells. The selections resulted in an antibody pool with near perfect selectivity (>99%) for the B lymphoma target cells. Randomly picked clones (72) revealed 7 unique antibody genotypes. Six of these rapidly induced apoptosis in target cells. Following the conversion to full IgGs, the antibodies were shown to be specific for HLA‐DR/DP, the B‐cell receptor μ chain and for CD54/ICAM‐1. The latter receptor was not previously associated with apoptotic properties in B‐cell lymphomas. Anti‐ICAM‐1 IgG induced apoptosis in a broad range of B lymphoma cell lines and were shown by immunohistochemistry to bind strongly to B lymphoma tissue obtained from 5 different B lymphoma patients. The recombinant IgG antibodies had affinities in the subnanomolar (0.3 nM) to nanomolar (3 nM) range. The described technology is generally applicable for the rapid isolation of high affinity human antibodies with specificity for differentially expressed cell surface receptors with intrinsic negative or positive signalling properties from naïve phage libraries. © 2006 Wiley‐Liss, Inc.
Familial risk of colon and rectal cancer in Iceland: Evidence for different etiologic factors?
Authors: Stefansson Tryggvi , Moller Pall H. , Sigurdsson Fridbjorn , Steingrimsson Eirikur , Eldon Bjarki Jónsson 
Published: February 2006

AbstractThe aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population‐based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46‐year period (1955–2000). The 2,770 colorectal cancer patients had 23,272 first‐degree relatives. Among first‐degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34–1.62) and rectal cancer (SIR 1.24, 95% CI 1.04–1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76–2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46–3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40–2.06). The added risk of colon cancer among first‐degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs. © 2006 Wiley‐Liss, Inc.
Antiangiogenic combination tumor therapy blocking αv‐integrins and VEGF‐receptor‐2 increases therapeutic effects in vivo
Authors: Strieth Sebastian , Eichhorn Martin E. , Sutter Arne , Jonczyk Alfred , Berghaus Alexander , Dellian Marc 
Published: February 2006

AbstractAnti‐angiogenesis is a promising strategy for cancer therapy currently evaluated in clinical trials. The aim of the study was to investigate the effects of an antiangiogenic combination therapy inhibiting αv‐integrins by a c(yclic)RGD‐peptide (EMD270179) and blocking VEGFR‐2 by SU5416 on tumor angiogenesis and progression in vivo. Experiments were performed in dorsal skinfold chamber preparations of Syrian golden hamsters (60 ± 5 g) bearing A‐Mel‐3 tumors. From day 3–10 after tumor‐cell implantation, animals (n = 6 per group) were treated by monotherapies using the cRGD‐peptide (114 mg/kg/day; i.p.), the VEGFR‐2 antagonist (6 mg/kg/day; i.p.) or by the combination of both monotherapies. A control group received only the solvent DMSO. Using intravital microscopy parameters of intratumoral microcirculation were analyzed on day 5, 7 and 10. In separate experiments subcutaneous tumor growth and metastasis formation was evaluated starting therapy on day 0. Functional vessel density was significantly reduced by the combination therapy compared to that by all other groups on day 10. Although intratumoral red blood cell velocity and vessel diameters were less affected, blood flow in vessel segments and the microcirculatory perfusion index were lower after combined therapy compared to controls. In addition, we observed a significantly stronger inhibition of subcutaneous tumor growth and metastasis formation using the combination therapy. These data clearly support the concept of antiangiogenic combination therapy and demonstrate that it may especially be effective when scheduled as an early or prophylactic treatment regimen, thus avoiding angiogenesis‐dependent tumor and metastasis initiation or tumor recurrence. © 2006 Wiley‐Liss, Inc.
Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues
Authors: Ulisse Salvatore , Delcros Jean‐Guy , Baldini Enke , Toller Matteo , Curcio Francesco , Giacomelli Laura , Prigent Claude , Ambesi‐Impiombato Francesco S. , D'Armiento Massimino , Arlot‐Bonnemains Yannick 
Published: February 2006

AbstractThe Aurora kinases are involved in the regulation of cell cycle progression, and alterations in their expression have been shown to associate with cell malignant transformation. In the present study, we demonstrated that human thyrocytes express all 3 Aurora kinases (A, B and C) at both protein and mRNA level and this expression is cell cycle‐regulated. An increase in the protein level of the 3 kinases was found, with respect to normal human thyrocytes (HTU5), in the human cell lines derived from follicular (FTC‐133), papillary (B‐CPAP) and anaplastic (8305C) thyroid carcinomas, but not in cells derived from a follicular adenoma (HTU42). These observations were mirrored in RT‐PCR experiments for Aurora‐A and B. In contrast, Aurora‐C mRNA levels were not significantly different among the different cell types analyzed, suggesting that posttranscriptional mechanism(s) modulate its expression. The expression at the protein level of all 3 Aurora kinases was significantly higher in 3 thyroid papillary carcinomas with respect to normal matched tissues obtained from the same patients. Similar modifications, at the mRNA level, could be observed in 7 papillary carcinoma tissues for Aurora‐A and B, but not for Aurora‐C. In conclusion, we demonstrated that normal human thyrocytes express all 3 members of the Aurora kinase family, and their expression is amplified in malignant thyroid cell lines and tissues. These results suggest that the Aurora kinases may play a relevant role in malignant thyroid cancers, and may represent a putative therapeutic target for thyroid neoplasms. © 2006 Wiley‐Liss, Inc.
Predicting 5‐fluorouracil chemosensitivity of liver metastases from colorectal cancer using primary tumor specimens: Three‐gene expression model predicts clinical response
Authors: Matsuyama Ryusei , Togo Shinji , Shimizu Daisuke , Momiyama Nobuyoshi , Ishikawa Takashi , Ichikawa Yasushi , Endo Itaru , Kunisaki Chikara , Suzuki Harukazu , Hayasizaki Yoshihide , Shimada Hiroshi 
Published: February 2006

AbstractWe identified genes related to 5‐fluorouracil (5‐FU) sensitivity in colorectal cancer and utilized these genes for predicting the 5‐FU sensitivity of liver metastases. Eighty‐one candidate genes involved in 5‐FU resistance in gastric and colon cancer cell lines were previously identified using a cDNA microarray. In this study, the mRNA expression levels of these 81 selected genes and the genes of 5‐FU‐related enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyltransferase (OPRT), were measured using real‐time quantitative RT‐PCR assays of surgically resected materials from primary colorectal tumors in 22 patients. Clinical responses were estimated by evaluating the effects of 5‐FU‐based hepatic artery injection (HAI) chemotherapy for synchronous liver metastases. Four genes (TNFRSF1B, SLC35F5, NAG‐1 and OPRT) had significantly different expression profiles in 5‐FU‐nonresponding and responding tumors (p < 0.05). A “Response Index” system using three genes (TNFRSF1B, SLC35F5 and OPRT) was then developed using a discriminate analysis; the results were well correlated with the individual chemosensitivities. Among the 11 cases with positive scores in our response index, 9 achieved a reduction in their liver metastases after 5‐FU‐based chemotherapy, whereas only 1 of the 11 cases with negative scores responded well to chemotherapy. Our “Response Index” system, consisting of TNFRSF1B, SLC35F5 and OPRT, has great potential for predicting the efficacy of 5‐FU‐based chemotherapy against liver metastases from colorectal cancer. © 2006 Wiley‐Liss, Inc.