bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Genetic Variation in Genes Implicated in the β-Catenin Destruction Complex with Risk of Breast Cancer
Authors: Wang Xianshu , Goode Ellen L. , Fredericksen Zachary S. , Vierkant Robert A. , Pankratz V. Shane , Liu-Mares Wen , Rider David N. , Vachon Celine M. , Cerhan James R. , Olson Janet E. , Couch Fergus J.
Published: August 2008

Aberrant Wnt/β-catenin signaling leading to nuclear accumulation of the oncogene product β-catenin is observed in a wide spectrum of human malignancies. The destruction complex in the Wnt/β-catenin pathway is critical for regulating the level of β-catenin in the cytoplasm and in the nucleus. Here, we report a comprehensive study of the contribution of genetic variation in six genes encoding the β-catenin destruction complex (APC, AXIN1, AXIN2, CSNK1D, CSNK1E, and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer Case-Control Study. A total of 79 candidate functional and tagging single nucleotide polymorphisms (SNP) were genotyped in 798 invasive cases and 843 unaffected controls. Of these, rs454886 in the APC tumor suppressor gene was associated with increased breast cancer risk (per allele odds ratio, 1.23; 95% confidence intervals, 1.05-1.43; Ptrend = 0.01). In addition, five SNPs in AXIN2 were associated with increased risk of breast cancer (Ptrend < 0.05). Haplotype-based tests identified significant associations between specific haplotypes in APC and AXIN2 (P ≤ 0.03) and breast cancer risk. Further characterization of the APC and AXIN2 variants suggested that AXIN2 rs4791171 was significantly associated with risk in premenopausal (Ptrend = 0.0002) but not in postmenopausal women. The combination of our findings and numerous genetic and functional studies showing that APC and AXIN2 perform crucial tumor suppressor functions suggest that further investigation of the contribution of AXIN2 and APC SNPs to breast cancer risk are needed. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2101–8)
Cyclooxygenase-2 Inhibitors in Colorectal Cancer Prevention: Point
Authors: Arber Nadir
Published: August 2008

The limited success of current treatments for most advanced common malignancies highlights the importance of cancer prevention. Clinical trials on cyclooxygenase (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for reducing cancer incidence, although not without associated side effects. The attractiveness of these drugs partly stems from an ability to engage multiple mechanisms of action by their potential to influence multiple components of the carcinogenesis pathway, from initiation to progression. There are two isoforms of the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves as a “housekeeper” of mucosal integrity, whereas COX-2 is an immediate early response gene that is highly inducible by neoplastic and inflammatory stimuli. COX-2 is significantly overexpressed in colorectal neoplasms, making it an attractive therapeutic target. The drug market has been revolutionized by the development of preparations targeted selectively against COX-2, and a proof of concept has been achieved. Chemoprevention of colorectal cancer is already possible with celecoxib, but it is still not the ultimate drug of choice especially because of the cardiovascular risk associated with COX-2 inhibitors. Better patient selection and more effective and safer drugs are needed. Celecoxib is probably best used in a subset of individuals at moderate to high colorectal cancer risk and low risk of cardiovascular disease. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1852–7)
Cancer Screening for Underserved Women: The Breast and Cervical Cancer Intervention Study
Authors: Hiatt Robert A. , Pasick Rena J. , Stewart Susan , Bloom Joan , Davis Patricia , Gardiner Philip , Luce Judith
Published: August 2008

Objective: To report on the effect of the Breast and Cervical Cancer Intervention Study (BACCIS), a multicomponent intervention conducted in the San Francisco Bay Area between 1992 and 1997.

Methods: BACCIS targeted ∼25,000 multiethnic, underserved women in eight neighborhoods and the public health clinics that served them. An outreach intervention using lay health worker peers and clinic provider inreach intervention to improve breast and cervical cancer screening were evaluated in a quasi-experimental, controlled trial with pretest and posttest household surveys of 1,599 and 1,616 women, respectively. Surveys were conducted in English, Spanish, Mandarin, and Cantonese.

Results: Analyses of community survey results showed no significant improvement in reported screening behaviors. Reports of mammography in the intervention areas in the previous 2 years, or for Pap smear in the previous 3 years, did not differ significantly (73-71% and 84-87%, respectively, for pretest and posttest surveys).

Conclusion: High baseline screening rates, lack of sensitive measures of change at the population level, contamination of the control group, and an imbalance of predictive factors at baseline contributed to the difficulty of assessing the value of the intervention. Lessons learned from this inconclusive study may be of value to future community intervention studies of cancer screening and other health behaviors in multiethnic underserved urban populations. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1945–9)
Effect of Nonmotorized Wheel Running on Mammary Carcinogenesis: Circulating Biomarkers, Cellular Processes, and Molecular Mechanisms in Rats
Authors: Zhu Zongjian , Jiang Weiqin , Sells Jennifer L. , Neil Elizabeth S. , McGinley John N. , Thompson Henry J.
Published: August 2008

The objective of this experiment was to identify circulating growth factors, hormones, and cellular and molecular mechanisms that account for the effects of physical activity on mammary carcinogenesis. A total of 120 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either a physically active or a sedentary control group. Individually housed rats were given free access to a nonmotorized, computer-controlled activity wheel and running behavior was reinforced by food reward. Rats self-determined their daily intensity and duration of running. Sedentary control rats received the same amount of food as the physically active rats to which they were paired. Physical activity reduced mammary cancer incidence (P = 0.015) and cancer multiplicity (P = 0.01). Physical activity induced changes in plasma insulin, insulin-like growth factor-I, and corticosterone, suggesting that mechanisms regulating glucose homeostasis were affected. Western blot analyses of mammary carcinomas revealed that proteins involved in cell proliferation were reduced (P < 0.001) and those involved in apoptosis via the mitochondrial pathway were elevated (P < 0.001) by physical activity. The hypothesis that these effects were mediated by activation of AMP-activated protein kinase, and down-regulation of protein kinase B, which collectively down-regulate the activity of the mammalian target of rapamycin, was evaluated. Evidence in support of this hypothesis was found in the Western blot analyses of mammary carcinomas, mammary gland, liver, and skeletal muscle. Collectively, these findings provide a rationale for additional studies of energy-sensing pathways in the elucidation of mechanisms that account for the inhibition of carcinogenesis by physical activity. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1920–9)
Prevalence of Genital Human Papilloma Virus Infection and Genotypes among Young Women in Sicily, South Italy
Authors: Ammatuna Pietro , Giovannelli Lucia , Matranga Domenica , Ciriminna Saverio , Perino Antonio
Published: August 2008

Infection with oncogenic human papilloma virus (HPV) types is a necessary cause of cervical cancer. This study assessed the prevalence of HPV infection and genotypes among 1,006 randomly selected women, ages 18 to 24 years, living in Sicily (south Italy). The overall HPV rate was 24.1% (95% confidence interval, 21.5-26.9). The most frequent types were HPV-16 (4.5%), HPV-53 (2.7%), and HPV-84 (2.6%). The prevalence of vaccine types HPV-6, HPV-11, and HPV-18 was 1.4%, 0.1%, and 1.3%, respectively. Cytologic abnormalities were uncommon (3.1%) and associated with HPV detection (P < 0.0001). The only risk factor for HPV infection was the number of sexual partners (women with 2-3 partners versus women with 1 partner: odds ratio, 3.86; 95% confidence interval, 2.45-6.09). Genital HPV infection is relatively high in young Italian women. The high prevalence of viral types other than vaccine types should be taken into account to ensure accurate postvaccine surveillance and early detection of a possible genotype replacement. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2002–6)
Metastatic Gastrointestinal Stromal Tumors in the Era of Imatinib: Improved Survival and Elimination of Socioeconomic Survival Disparities
Authors: Artinyan Avo , Kim Joseph , Soriano Perry , Chow Warren , Bhatia Smita , Ellenhorn Joshua D.I.
Published: August 2008

Background: Imatinib was approved in 2002 for unresectable and metastatic gastrointestinal stromal tumors. Our objective was to determine if the introduction of imatinib coincided with improved survival from metastatic gastrointestinal stromal tumor in the U.S. population and in specific socioeconomic groups.

Methods: Query of the Surveillance, Epidemiology, and End Results registry identified 552 patients with metastatic gastrointestinal stromal tumor between 1995 and 2004. Year of diagnosis was categorized into two periods, 1995 to 2000 and 2001 to 2004, to account for the effect of imatinib. Kaplan-Meier and multivariate Cox regression analyses were used to examine differences in survival between periods and among socioeconomic groups.

Results: Median survival increased from 12 to 33 months from 1995 to 2000 to 2001 to 2004 (P < 0.001); survival at 47 months increased from 21% to 41%, respectively (P < 0.001). Median survival times for White, Black, Hispanic, and Asian or Pacific Islander, and for low-, middle-, and high-income groups increased significantly in the era of imatinib (all P < 0.05). On multivariate analysis, Black race [hazard ratio, 1.96; 95% confidence interval (95% CI), 1.15-3.32; P = 0.013], Hispanic race (hazard ratio, 2.11; 95% CI, 1.14-3.88; P = 0.017), and low income (hazard ratio, 1.81; 95% CI, 1.13-2.89; P = 0.014) were associated with the poorest survival during the 1995 to 2000 period. During 2001 to 2004, these disparities in survival were no longer statistically apparent.

Conclusions: Survival from metastatic gastrointestinal stromal tumor has improved significantly in the era of imatinib. This improvement has been uniform across all socioeconomic groups, with concomitant elimination of socioeconomic survival disparities potentially due to an assistance program intended to provide universal access to imatinib therapy. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2194–201)
Circulating 2-Hydroxy- and 16α-Hydroxy Estrone Levels and Risk of Breast Cancer among Postmenopausal Women
Authors: Eliassen A. Heather , Missmer Stacey A. , Tworoger Shelley S. , Hankinson Susan E.
Published: August 2008

Circulating estrogens are associated with breast cancer risk in postmenopausal women. Given that estrogen metabolites are potentially both mitogenic and genotoxic, it is possible that plasma levels of estrogen metabolites are related to breast cancer risk. We conducted a prospective, nested case-control study within the Nurses' Health Study. Blood samples, collected in 1989 to 1990, were assayed for 2-OH and 16α-OH estrone among 340 cases and 677 matched controls not taking postmenopausal hormones. Multivariate relative risks (RR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression, adjusting for breast cancer risk factors. Neither 2-OH nor 16α-OH estrone concentrations were significantly associated with breast cancer risk overall (top versus bottom quartile: RR, 1.19; 95% CI, 0.80-1.79; Ptrend = 0.40 for 2-OH estrone and RR, 1.04; 95% CI, 0.71-1.53; Ptrend = 0.81 for 16α-OH estrone). The ratio between the two metabolites (2-OH:16α-OH estrone) was similarly unrelated to risk overall (1.30; 95% CI, 0.87-1.95; Ptrend = 0.35). Although no associations were detected among women with estrogen receptor (ER)–positive/progesterone receptor (PR)–positive tumors, significant positive associations were observed for 2-OH estrone and the 2-OH:16α-OH estrone ratio among women with ER-negative/PR-negative tumors (RR, 3.65; 95% CI, 1.23-10.81; Ptrend = 0.01; Pheterogeneity = 0.02 for 2-OH estrone; RR, 3.70; 95% CI, 1.24-11.09; Ptrend = 0.004; Pheterogeneity = 0.005 for 2-OH:16α-OH estrone). These data do not support the hypothesized inverse associations with 2-OH estrone and the 2-OH:16α-OH estrone ratio or the hypothesized positive association with 16α-OH estrone. The significant positive associations with 2-OH estrone and the 2-OH:16-OH estrone ratio among women with ER-negative/PR-negative tumors needs to be replicated in future studies. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2029–35)
No Acute and Persistent DNA Damage after an Ironman Triathlon
Authors: Reichhold Stefanie , Neubauer Oliver , Ehrlich Veronika , Knasmüller Siegfried , Wagner Karl-Heinz
Published: August 2008

During acute and strenuous exercise, the enhanced formation of reactive oxygen species can induce damage to lipids, proteins, and nucleic acids. The aim of this study was to investigate the effect of an Ironman triathlon (3.8 km swim, 180 km cycle, 42 km run), as a prototype of ultra-endurance exercise, on DNA stability. As biomarkers of genomic instability, the number of micronuclei, nucleoplasmic bridges, and nuclear buds were measured within the cytokinesis-block micronucleus cytome assay in once-divided peripheral lymphocytes of 20 male triathletes. Blood samples were taken 2 days before, within 20 min after the race, and 5 and 19 days post-race. Overall, the number of micronuclei decreased (P < 0.05) after the race, remained at a low level until 5 days post-race, and declined further to 19 days post-race (P < 0.01). The frequency of nucleoplasmic bridges and nuclear buds did not change immediately after the triathlon. The number of nucleoplasmic bridge declined from 2 days pre-race to 19 days post-exercise (P < 0.05). The frequency of nuclear buds increased after the triathlon, peaking 5 days post-race (P < 0.01) and decreased to basic levels 19 days after the race (P < 0.01). The results suggest that an Ironman triathlon does not cause long-lasting DNA damage in well-trained athletes. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1913–9)
Hemoglobin Adducts of Benzene Oxide in Neonatal and Adult Dried Blood Spots
Authors: Funk William E. , Waidyanatha Suramya , Chaing Shu H. , Rappaport Stephen M.
Published: August 2008

Adducts of reactive chemicals with hemoglobin (Hb) or human serum albumin can be used as biomarkers of internal doses of carcinogens. Because dried blood spots are easier to collect and store than conventional venous blood samples, they encourage applications of biomarkers of exposure in large epidemiologic studies. In addition, neonatal dried blood spot can be used to investigate chemical exposures in utero. Here, we report a simple method to isolate Hb from dried blood spot with high recovery and purity using the addition of ethanol to aqueous dried blood spot extracts. To prove the concept that dried blood spot–derived proteins can be used to assay for adducts, we measured Hb adducts of benzene oxide, a reactive metabolite of the ubiquitous air pollutant benzene in nine neonatal and nine adult dried blood spots (from volunteer subjects), using a gas chromatography–mass spectrometry method that we had previously developed. For comparison, benzene oxide–Hb adducts were measured in the same nine adult subjects using Hb that had been isolated and purified using our conventional method for venous blood. The geometric mean of benzene oxide–Hb levels in all dried blood spot samples ranged from 27.7 to 33.1 pmol/g globin. Neither of the comparisons of mean (logged) benzene oxide–Hb levels between sources (adult conventional versus adult dried blood spot and adult dried blood spot versus newborn dried blood spot) showed a significant difference. Based upon the estimated variance of the benzene oxide–Hb levels, we had 80% power to detect a 1.7-fold difference in geometric mean levels of benzene oxide–Hb in our sample of nine subjects. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1896–901)
The Role of the BRCA2 Gene in Susceptibility to Prostate Cancer Revisited
Authors: Ostrander Elaine A. , Udler Miriam S.
Published: August 2008

Prostate cancer is a genetically complex disease with multiple predisposing factors affecting presentation, progression, and outcome. Epidemiologic studies have long shown an aggregation of breast and prostate cancer in some families. More recently, studies have reported an apparent excess of prostate cancer cases among BRCA2 mutation–carrying families. Additionally, population-based screens of early-onset prostate cancer patients have suggested that the prevalence of deleterious BRCA2 mutations in this group is 1% to 2%, imparting a significantly increased risk of the disease compared with noncarrier cases. However, studies of high-risk prostate cancer families suggest that BRCA2 plays at most a minimal role in these individuals, highlighting the potential genetic heterogeneity of the disease. In this commentary, we review the current literature and hypotheses surrounding the relationship between BRCA2 mutations and susceptibility to prostate cancer and speculate on the potential for involvement of additional genes. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1843–8)
Chemokine Decoy Receptor D6 Plays a Negative Role in Human Breast Cancer
Authors: Wu Feng-Ying , Ou Zhou-Luo , Feng Lan-Yun , Luo Jian-Min , Wang Lei-Ping , Shen Zhen-Zhou , Shao Zhi-Min
Published: August 2008

Chemokine binding protein D6 is a promiscuous decoy receptor that can inhibit inflammation in vivo; however, the role it plays in cancer is not well known yet. In this study, we showed for the first time that human breast cancer differentially expressed D6 and the expression could be regulated by some cytokines. More importantly, overexpression of D6 in human breast cancer cells inhibits proliferation and invasion in vitro and tumorigenesis and lung metastasis in vivo. This inhibition is associated with decreased chemokines (e.g., CCL2 and CCL5), vessel density, and tumor-associated macrophage infiltration. Furthermore, D6 expression is inversely correlated to lymph node metastasis as well as clinical stages, but positively correlated to disease-free survival rate in cancer patients. Therefore, D6 plays a negative role in the growth and metastasis of breast cancer. (Mol Cancer Res 2008;6(8):1276–88)
Effects of Palifermin on Antitumor Activity of Chemotherapeutic and Biological Agents in Human Head and Neck and Colorectal Carcinoma Xenograft Models
Authors: Brake Rachael , Starnes Charlie , Lu John , Chen Danlin , Yang Suijin , Radinsky Robert , Borges Luis
Published: August 2008

Damage to the gastrointestinal mucosa is a common dose-limiting toxicity of several anticancer therapies. Until recently, adequate control of oral mucositis was considered a significant unmet medical need, with most available treatments providing only palliative benefits without protecting the gastrointestinal epithelium from the damaging effects of cancer therapy. In 2005, palifermin [recombinant human keratinocyte growth factor (KGF)] was approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. Current trials are investigating the use of palifermin in solid tumor settings. The objective of this study was to determine whether combining palifermin with different chemotherapeutic or biological agents affected the antitumor activity of these agents in human head and neck (FaDu) and colorectal (HT29) carcinoma xenograft models. Nude CD1 mice were injected with 1 × 107 of either FaDu or HT29 cells, which express both KGF and epithelial growth factor receptors. Animals were treated with palifermin in various combinations with chemotherapeutic (5-fluorouracil and cisplatin) and/or biological (bevacizumab, cetuximab, and panitumumab) agents. Palifermin alone had no effect on either FaDu or HT29 tumor growth. Palifermin did not affect the therapeutic efficacy of 5-fluorouracil, cisplatin, cetuximab, bevacizumab, or panitumumab in any of the two- or three-way drug combinations tested in either model. The results of this study showed that palifermin did not promote the growth of two carcinoma cell lines that express functional KGF receptors and did not protect these tumor cells from the antitumor effects of several chemotherapeutic and biological agents. (Mol Cancer Res 2008;6(8):1337–46)
c-Jun Is Critical for the Progression of Osteosarcoma: Proof in an Orthotopic Spontaneously Metastasizing Model
Authors: Dass Crispin R. , Khachigian Levon M. , Choong Peter F.M.
Published: August 2008

The oncogene c-Jun has been found to be up-regulated in a variety of cancers including osteosarcoma. DNA enzymes (DNAzymes) are oligonucleotides capable of specific catalysis of target mRNA. A c-Jun DNAzyme inhibited the growth and metastasis of osteosarcoma in an orthotopic spontaneously metastasizing model of the disease. c-Jun down-regulation–mediated apoptosis in osteosarcoma cells involved caspase-1, caspase-2, and caspase-8, but not the Fas/FasL pathway. Clinically, knockdown of c-Jun with DNAzymes may proffer an improved treatment outcome for these tumors originating in bone. (Mol Cancer Res 2008;6(8):1289–92)
Cross-talk between Aryl Hydrocarbon Receptor and Mitogen-Activated Protein Kinase Signaling Pathway in Liver Cancer through c-raf Transcriptional Regulation
Authors: Borlak Jürgen , Jenke Hans Stephan
Published: August 2008

c-raf is a serine-threonine kinase and a downstream effector of ras signaling. This kinase plays an essential role in cell proliferation, differentiation, and apoptosis. In the past, we reported induction of c-raf gene expression in rat liver cancer on treatment with a mixture of aryl hydrocarbon receptor (AhR) agonists. This prompted our interest in investigating the role of AhR in the transcriptional regulation of c-raf. Initially, we cloned the rat c-raf promoter and sequenced the genomic DNA and cDNA by Southern blotting and capillary electrophoresis. Then, a genetic algorithm was applied to search for putative AhR-binding sites. DNA-binding activity of AhR was confirmed by electromobility shift assay. We also studied c-raf gene expression in rat hepatoma cell lines with functional and/or devoid AhR and in primary human and rat hepatocyte cultures. Overall, we identified five and three AhR-binding sites in the human and rat c-raf gene, respectively. Treatment of hepatocyte cultures with the AhR antagonist resveratrol reduced DNA binding of AhR. Only rat hepatoma cells with functional AhR responded to 1 nmol/L 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment with >10-fold c-raf mRNA induction. Treatment of human and rat hepatocyte cultures with various AhR-activating chemicals resulted in induction of c-raf gene expression, albeit at different levels. Taken collectively, we show AhR to be a master regulator of c-raf and propose cross-talk between AhR and the mitogen-activated protein kinase signaling pathway in chemically induced hepatocarcinogenesis. (Mol Cancer Res 2008;6(8):1326–36)
Cadherin-11 Promotes the Metastasis of Prostate Cancer Cells to Bone
Authors: Chu Khoi , Cheng Chien-Jui , Ye Xiangcang , Lee Yu-Chen , Zurita Amado J. , Chen Dung-Tsa , Yu-Lee Li-Yuan , Zhang Sui , Yeh Edward T. , Hu Mickey C-T. , Logothetis Christopher J. , Lin Sue-Hwa
Published: August 2008

Bone is the most common site of metastases from prostate cancer. The mechanism by which prostate cancer cells metastasize to bone is not fully understood, but interactions between prostate cancer cells and bone cells are thought to initiate the colonization of metastatic cells at that site. Here, we show that cadherin-11 (also known as osteoblast-cadherin) was highly expressed in prostate cancer cell line derived from bone metastases and had strong homophilic binding to recombinant cadherin-11 in vitro. Down-regulation of cadherin-11 in bone metastasis–derived PC3 cells with cadherin-11–specific short hairpin RNA (PC3-shCad-11) significantly decreased the adhesion of those cells to cadherin-11 in vitro. In a mouse model of metastasis, intracardiac injection of PC3 cells led to metastasis of those cells to bone. However, the incidence of PC3 metastasis to bone in this model was reduced greatly when the expression of cadherin-11 by those cells was silenced. The clinical relevance of cadherin-11 in prostate cancer metastases was further studied by examining the expression of cadherin-11 in human prostate cancer specimens. Cadherin-11 was not expressed by normal prostate epithelial cells but was detected in prostate cancer, with its expression increasing from primary to metastatic disease in lymph nodes and especially bone. Cadherin-11 expression was not detected in metastatic lesions that occur in other organs. Collectively, these findings suggest that cadherin-11 is involved in the metastasis of prostate cancer cells to bone. (Mol Cancer Res 2008;6(8):1259–67)
Retrograde Jejuno-Jejunal Intussusception after Total Gastrectomy
Authors: Yoneda Akira , Kamohara Yukio , Taniguchi Ken , Maeda Junpei , Akashi Arifumi , Inoue Keiji , Kohara Norihiro , Miyata Akimi , Kanematsu Takashi
Published: August 2008

An eighty-year-old female was transferred to the hospital after experiencing abdominal pain and nausea. She had had a history of total gastrectomy for gastric cancer 14 years previously. Abdominal X-ray revealed a localized expansion of the small bowel. Computed tomography revealed a mass with a lamellar structure in a concentric circle. With a tentative diagnosis of small bowel obstruction due to intussusception, she underwent emergency operation. Laparotomy revealed a retrograde jejuno-jejunal intussusception. Bowel resection was performed due to the severe ischemic damage. All reported intussusception cases after total gastrectomy displayed retrograde characteristics and could occur both during the early and late period after surgery. It is important to consider the possibility of intussusception for patients presenting with acute abdomen who have previously undergone gastric resection.
Budd-Chiari Syndrome: Two Cases with Different Courses
Authors: Inomata Shinjiro , Takeyama Yasuaki , Tanaka Takashi , Ueda Shu-ichi , Morihara Daisuke , Nishizawa Shinya , Matsumoto Teruo , Anan Akira , Nishimura Hirokatsu , Irie Makoto , Iwata Kaoru , Shakado Satoshi , Sohda Tetsuro , Higashihara Hideyuki , Okazaki Masatoshi , Sakisaka Shotaro
Published: August 2008

We report two cases of Budd-Chiari syndrome. Case 1: A 57-year-old man presented with leg edema and esophageal varices. Cavography showed obstruction of the inferior vena cava with antiphospholipid syndrome. Further, the patient showed positive serology for hepatitis C virus and consumed large quantities of alcohol. Percutaneous transluminal angioplasty was performed on this patient and anticoagulants administered; leg edema and esophageal varices were ameliorated although liver biopsy showed cirrhosis without evident congestion. More than 9 months since the diagnosis, restenosis of the inferior vena cava has not occurred. Case 2: A 73-year-old woman presented abdominal pain but no edema or varices. Cavography showed membranous obstruction of the inferior vena cava which required no therapy. Manifestation of portal hypertension was not present and liver function was maintained although liver biopsy showed obvious congestion. These cases showed untypical features against histopathology, and careful observation will be required for emergence of hepatocellular carcinoma.
Correlation of Cutaneous Lesions with Clinical Radiological and Urodynamic Findings in the Prognosis of Underlying Spinal Dysraphism Disorders
Authors: Sasani Mehdi , Asghari Bahloul , Asghari Yalda , Afsharian Ruya , Ozer Ali Fahir
Published: August 2008

Spinal dysraphism is characterized by a lack of fusion of the vertebral arches that occurs in the absence of spinous processes with variable amounts of lamina. Here, we retrospectively present the importance of cutaneous lesions and their correlation with clinical presentation, radiological examination and urodynamic assessment. We retrospectively reviewed 612 (6.12%) cases with skin lesions from 10,000 consecutive live-born children seen at two institutions between January 1998 and March 2005. We divided all children into a control group and three groups based on clinical assessment, radiological examination and urodynamic evaluation results. Neurological deficits were identified in 113 (18.46%) children, while spinal dysraphism disorders, tethered cord syndrome and associated orthopedic malformations were found in 171 (27.94%), 119 (19.45%) and 28 (4.57%) patients, respectively. The incidence of tethered cord with lumbosacral dimple lesions over the sacrum (32/119, 26.65% of patients) was 3.5-fold higher than that of lesions found over the coccyx (9/119, 7.5% of patients). Uroneurological symptoms were found in 207/612 (33.82%) children. Urodynamic assessment revealed decreased bladder capacity in 10% of patients, detrusor hyperflexia during filling in 47% and a low-compliance detrusor in 71%. Discordance between ultra- sonography and MRI was found in 16.58% of patients. Spinal cord untethering was performed for 109 patients. Nearly all children with resolution were at the end of their follow-up period (24 months). Retethering occurred in 21 (19.26%) patients, and a second untethering surgery was performed in 12 patients. When spina bifida was associated with lumbar skin lesions, there may have been an increased incidence of tethered cord and other spinal cord disorders. MRI scans are more reliable and give an exact diagnosis of tethered cord. Neurological and uroneurological instability are ultimately a clinical diagnosis, and there is controversy about their indications for surgery. However, the correlation between urodynamic assessment and cutaneous lesions with a tethered cord found by MRI examination allow for an early diagnosis and the possibility of prompt treatment.
Descriptive Epidemiology of Childhood Central Nervous System Tumours in Tunisia
Authors: Bellil Salma , Limaiem Faten , Mahfoudhi Houaïda , Bellil Khadija , Chelly Inès , Mekni Amina , Jemel Hafedh , Khaldi Moncef , Haouet Slim , Zitouna Moncef , Kchir Nidhameddine
Published: August 2008

Introduction: Central nervous system tumours represent 20% of all childhood cancers, and are the second most common group of neoplasms after leukaemias. Objective: To describe epidemiological characteristics of central nervous system tumours in a paediatric Tunisian population. Patients and Methods: A retrospective study of 492 childhood central nervous system tumours operated between 1990 and 2004 was undertaken. We investigated the age-related location, gender distribution and the histology of all tumours, and adopted the latest WHO classification (2007) in grouping all the tumours. Results: There were 488 primary and 4 secondary tumours; 426 (86.6%) were intracranial and 66 (13.4%) were intraspinal. Of the 426 intracranial tumours, 214 (50.24%) were supratentorial and 212 (49.76%) were infratentorial. The median age at diagnosis was 8 years, with a male:female ratio of 1.14:1. Low-grade tumours (WHO I/II) constituted 67.3% of all lesions and the rest (32.7%) were high-grade tumours (WHO III/IV). The most common tumour found in our series was astrocytoma (38%), followed by medulloblastoma (16.2%), then ependymoma (6.9%), cystic tumours (6.3%) and craniopharyngioma (5.3%). The overall 5-year survival rate was 45% with a mean follow-up period of 36 months. Conclusion: In our patient population, the incidence and distribution of central nervous system tumours were similar to those reported in literature. Overall survival rates varied according to tumour location and histopathology.
Successful Multimodal Therapies for a Primary Atypical Teratoid/Rhabdoid Tumor in the Cervical Spine
Authors: Yano Shunsuke , Hida Kazutoshi , Kobayashi Hiroyuki , Iwasaki Yoshinobu
Published: August 2008

Atypical teratoid/rhabdoid tumor (AT/RT) occurring in the central nervous system is a high-grade malignant tumor, and its prognosis is poor for patients younger than 3 years of age. In this article, we present a case of infant AT/RT in the cervical spine and its successful treatment by intensive chemotherapy. The patient, a 1.75-year-old girl, developed an acute, progressive tetraparesis. MRI revealed a large, intradural mass in the cervical spine.Total surgical resection was performed, and the specimen was diagnosed as AT/RT. Continuously, she received intensive chemotherapy using thiotepa with autologous bone marrow transplantation. At the age of nearly 3 years, she received radiation therapy to the local tumor bed and craniospinal axis. She is now 4 years old and has been maintained in complete remission with a good clinical course and no neurological deficit. The success of this treatment for the patient was that we could prevent tumor recurrence until she was able to receive radiotherapy.
Chiasmal Cavernoma: A Rare Cause of Acute Visual Loss Improved by Prompt Surgery
Authors: Newman Hadas , Nevo Margalit , Constantini Shlomi , Maimon Shimon , Kesler Anat
Published: August 2008

We report a 16-year-old healthy boy who presented with sudden loss of vision in both eyes, accompanied by a mild headache. Magnetic resonance imaging showed a chiasmal apoplexy. An urgent craniotomy revealed a cavernous malformation of the chiasm, which was evacuated. There was a subsequent dramatic improvement in bilateral visual acuity and visual field defects. This case report emphasizes the importance of rapid diagnosis and surgery of an anterior visual pathway cavernous malformation.
Ghosts of the Past I: Some Muscles and Fasciae in the Head Domain
Authors: Oxnard C.E. , Franklin D.
Published: August 2008

Humans alone among primates lack a superficial head of the temporalis muscle, although a complete superficial muscle is present in 1% of humans and an incomplete one in 8%. Yet the temporal fascia of normal humans contains all the fascial sheets associated with that head even though it is absent. The implication is that humans have lost the superficial temporal muscle, that this is evident from the retention of the fascial sheets, and that the muscular variations represent situations where the muscle has persisted to some degree. Molecular factors in the head domain that are responsible for the development of the muscles of mastication (myosin heavy chain 16) are likewise different in humans than in all non-human species and seem to be responsible for the reduction of those muscles in humans. Could the loss of the superficial portion of the temporalis muscle be a component of this reduction? Could the uncommon muscular variations result from some slight persistence of the prior molecular situation? Could the persistence of the fascial sheets, even when the muscle is absent, be because the molecular factors responsible for connective tissues are not the same as those responsible for muscles? How much of all this can be visualised in the fossil record? Skeletal dimensions of the temporal fossa, partly related to the temporal muscle size, imply that it may be possible to determine in which fossils temporal muscle reduction has occurred. Likewise, surface features of the bone in modern humans without a superficial muscular component but with a strong complex fibrous element suggest that it might be possible to determine, in any fossil in which the surface preservation is good enough, how far back this situation may have persisted. It is already known that myosin heavy chain molecular dating suggests that the muscle reduction may have occurred about 2.4 million years ago.
Response to Reintroduction of Cetuximab in 5 Patients with Advanced, Chemotherapy-Resistant, Colorectal Cancer without Progressive Disease following First-Line Therapy with a Cetuximab-Containing Regimen
Authors: Kaechele Volker , von Wichert Goetz , Adler Guido , Seufferlein Thomas
Published: August 2008

Objective: We aimed to determine the response to cetuximab in advanced, chemotherapy-resistant, colorectal cancer following successful first-line therapy with the antibody. Methods: Five patients with metastatic colorectal cancer were treated with a cetuximab-containing regimen after failure of several conventional chemotherapies. Results: These patients had been successfully treated with cetuximab as first-line therapy, and the antibody was then discontinued without disease progression. No severe toxicities were observed upon reexposure to cetuximab. Partial response was noted in 1 patient and tumor stabilization in 2 patients. Conclusion: Reintroduction of cetuximab in combination with chemotherapy is safe and efficacious in patients with colorectal cancer whose tumors were not refractory to a prior cetuximab-containing therapy.
Identifying Promoter Elements Necessary for Enamelin Tissue-Specific Expression
Authors: Papagerakis Petros , Hu Yuanyuan , Ye Ling , Feng Jerry Q. , Simmer James P. , Hu Jan C.-C.
Published: August 2008

Enamel development requires the strictly regulated spatiotemporal expression of genes encoding enamel matrix proteins. The mechanisms orchestrating the initiation and termination of gene transcription at each specific stage of amelogenesis are unknown. In this study, we identify cis- regulatory regions necessary for normal enamelin (Enam) expression. Sequence analysis of the Enam promoter 5′-noncoding region identified potentially important cis-regulatory elements located within 5.2 kb upstream of the Enam translation initiation site. DNA constructs containing 5.2 or 3.9 kb upstream of the Enam translation initiation site were linked to an LacZ reporter gene and used to generate transgenic mice. The 3.9-kb Enam-LacZ transgenic lines showed no expression in ameloblasts, but ectopic LacZ staining was detected in osteoblasts. In contrast, the 5.2-kb Enam-LacZ construct was sufficient to mimic the endogenous Enam ameloblast-specific expression pattern. Our study provides new insights into the molecular control of Enam cell- and stage-specific expression.
Lysosomal Protease Expression in Mature Enamel
Authors: Tye Coralee E. , Lorenz Rachel L. , Bartlett John D.
Published: August 2008

The enamel matrix proteins (amelogenin, enamelin and ameloblastin) are degraded by matrix metalloproteinase-20 and kallikrein-4 during enamel development and mature enamel is virtually protein free. The precise mechanism of removal and degradation of the enamel protein cleavage products from the matrix, however, remains poorly understood. It has been proposed that receptor-mediated endocytosis allows for the cleaved proteins to be removed from the matrix during enamel formation and then transported to the lysosome for further degradation. This study aims to identify lysosomal proteases that are present in maturation-stage enamel organ. RNA from first molars of 11-day-old mice was collected and expression was initially assessed by RT-PCR and then quantified by qPCR. The pattern of expression of selected proteases was assessed by immunohistochemical staining of demineralized mouse incisors. With the exception of cathepsin G, all lysosomal proteases assessed were expressed in maturation-stage enamel organ. Identified proteases included cathepsins B, D, F, H, K, L, O, S and Z. Tripeptidyl peptidases I and II as well as dipeptidyl peptidases I, II, III and IV were also found to be expressed. Immunohistochemical staining confirmed that the maturation-stage ameloblasts express cathepsins L and S and tripeptidyl peptidase II. Our results suggest that the ameloblasts are enriched by a large number of lysosomal proteases at maturation that are likely involved in the degradation of the organic matrix.
Correlation of Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinase Expression in Ileal Carcinoids, Lymph Nodes and Liver Metastasis with Prognosis and Survival
Authors: Voland Petra , Besig Sophie , Rad Roland , Braun Thomas , Baur Dorothee M. , Perren Aurel , Langer Rupert , Höfler Heinz , Prinz Christian
Published: August 2008

Purpose: Ileal carcinoids are gut epithelial tumors originating from serotonin-containing enterochromaffin (EC) cells. Therapeutic options for effectively inhibiting the growth and spread of metastatic carcinoids are still limited. We aimed to identify the role of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) during tumor development and metastasis. Patients and Methods: Tissue samples were obtained from surgically treated patients. Expression of the EC-cell marker, vesicular monoamine transporter-1 (VMAT-1), was used to verify ileal carcinoids. We investigated the differential expression of MMP-2, 7, 9, 11, and 13 and their endogenous inhibitors (TIMP-1, 2, and 3) by quantitative real-time RT-PCR in 25 primary tumors, their corresponding lymph node metastases and/or liver metastases and matched normal mucosa. Results: Significantly increased expression of VMAT-1, MMP-2, MMP-11, TIMP-1 and TIMP-3 was determined by quantitative RT-PCR in EC-cell carcinoids compared to normal intestinal mucosa (p < 0.05). In contrast, MMP-2 and MMP-9 as well as TIMP-1, TIMP-2, and TIMP-3 expression in primary tumors of patients with liver metastases (M1) was significantly lower than in patients lacking liver metastases (M0). EC-cell tumors were significantly larger in the M1 group of tumors, while VMAT-1 expression was significantly decreased. We found an inverse correlation between tumor size and prognosis. Univariate analysis further revealed that decreased expression of VMAT-1, MMP-2 and TIMP-3 in primary tumors was significantly associated with a reduced survival time of the patients. Conclusion: Our data reveal that MMP-2 and TIMP-3 expression together with VMAT-1 expression are of potential prognostic and clinical value in ileal carcinoids.
Is There a Link between Insulin Resistance and Chronic Kidney Disease in Men with Treated Hypertension? Analysis of 5-Year Data
Authors: Mohteshamzadeh Mobin , Wong Christopher , Whiticar Rebecca , Thomas Simon
Published: August 2008

Background/Aims: Hypertension, chronic kidney disease (CKD) and cardiovascular disease (CVD) have reached epidemic proportions globally. Patients with CKD are at increased risk of CVD and yet conventional factors have yet to be linked with the risk associated with patients with CKD. The aim of this research was to establish whether there is a link between insulin resistance (IR) and estimated glomerular filtration rate (eGFR), and assess whether insulin-resistant subjects experience a more rapid deterioration in eGFR. Methods: IR was determined using HOMA-IR (homeostasis model assessment for IR) in normoglycaemic, male subjects with treated hypertension and correlated with clinical variables over a period of 5 years. Results: 106 subjects were assigned to three groups according to insulin sensitivity. Patients with IR had a higher body mass index, fasting glucose, triglyceride and lower HDL cholesterol. Half of the insulin-resistant patients developed an impaired fasting glucose by 1 year and 14% were being treated for type 2 diabetes mellitus by 5 years. Baseline and 5-year data revealed that there was no link between IR and eGFR, which deteriorated equally in all groups. Conclusion: We established that both CKD and IR are common and that the majority of subjects with IR developed impaired fasting glucose or type 2 diabetes mellitus in only 5 years. Although eGFR deteriorated in all groups, no link was found between eGFR and IR.
Mineral Surface in Calcified Plaque Is Like That of Bone
Authors: Duer Melinda J. , Friščić Tomislav , Proudfoot Diane , Reid David G. , Schoppet Michael , Shanahan Catherine M. , Skepper Jeremy N. , Wise Erica R.
Published: August 2008

Objectives—

Cell biological studies demonstrate remarkable similarities between mineralization processes in bone and vasculature, but knowledge of the components acting to initiate mineralization in atherosclerosis is limited. The molecular level microenvironment at the organic-inorganic interface holds a record of the mechanisms controlling mineral nucleation. This study was undertaken to compare the poorly understood interface in mineralized plaque with that of bone, which is considerably better characterized.

Methods and Results—

Solid state nuclear magnetic resonance (SSNMR) spectroscopy provides powerful tools for studying the organic-inorganic interface in calcium phosphate biominerals. The rotational echo double resonance (REDOR) technique, applied to calcified human plaque, shows that this interface predominantly comprises sugars, most likely glycosaminoglycans (GAGs). In this respect, and in the pattern of secondary effects seen to protein (mainly collagen), calcified plaque strongly resembles bone.

Conclusion—

The similarity between biomineral formed under highly controlled (bone) and pathological (plaque) conditions suggests that the control mechanisms are more similar than previously thought, and may be adaptive. It is strong further evidence for regulation of plaque mineralization by osteo/chondrocytic vascular smooth muscle cells.
E-Cadherin/β-Catenin/T-Cell Factor Pathway Is Involved in Smooth Muscle Cell Proliferation Elicited by Oxidized Low-Density Lipoprotein
Authors: Bedel Aurélie , Nègre-Salvayre Anne , Heeneman Sylvia , Grazide Marie-Hélène , Thiers Jean-Claude , Salvayre Robert , Maupas-Schwalm Françoise
Published: August 2008

The E-cadherin/β-catenin/T-cell factor (Tcf) signaling pathway plays a crucial role in embryogenesis and carcinogenesis and has recently emerged in atherosclerosis. The aim of this work was to investigate whether this signaling pathway is involved in smooth muscle cell proliferation induced by oxidized low-density lipoprotein (LDL). In human aortic smooth muscle cells, mitogenic concentration of mildly oxidized LDL induced the activation of β-catenin, as assessed by the dissociation of the β-catenin/cadherin complex, and the concomitant rise of active β-catenin in the cytosol. The oxidized LDL–induced rise of active β-catenin required metalloproteinase activation, as well as epidermal growth factor receptor and Src signaling, as assessed by the use of pharmacological inhibitors and cells overexpressing a SrcK-inactive form. The concomitant phosphatidylinositol 3-kinase/Akt activation and glycogen synthase kinase 3-β phosphorylation induced the inhibition of the proteasomal degradation of β-catenin. Then active β-catenin associated with Tcf4 and translocated into the nucleus. This enhanced the expression of the cell cycle activator cyclin D1. This crucial role of β-catenin in the mitogenic effect of oxidized LDL was confirmed by silencing β-catenin by specific small interfering RNA that blocked DNA synthesis. Immunohistochemistry staining of stable and disrupted plaques from carotid endarterectomy sections showed a correlation between active β-catenin and Ki67, a proliferation marker, and a more intense staining in the smooth muscle cell layer surrounding the lipid core of disrupted plaques. In conclusion, the β-catenin pathway is required for the mitogenic effect of oxidized LDL on human aortic smooth muscle cells. This study highlights the putative important role of the E-cadherin/β-catenin/Tcf signaling pathway in atherosclerosis.