bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oldest known case of metastasizing prostate carcinoma diagnosed in the skeleton of a 2,700‐year‐old Scythian king from Arzhan (Siberia, Russia)
Authors: Schultz Michael , Parzinger Hermann , Posdnjakov Dmitrij V. , Chikisheva Tatjana A. , Schmidt‐Schultz Tyede H. 
Published: October 2007

AbstractTo determine whether a 2,700‐year‐old tumor can be reliably diagnosed using microscopic and proteomic techniques and whether such prostate carcinomas show the same morphological pattern at the micro‐level as modern‐day carcinomas, this case was investigated. A 40–50‐year‐old Scythian king who lived during the Iron Age in the steppe of Southern Siberia (Russia) suffered from macroscopically visible osteoblastic and osteoclastic lesions throughout his entire skeleton. Macro‐morphological (macroscopy, endoscopy, radiology) and micro‐morphological techniques (histology, scanning‐electron microscopy) as well as proteomic techniques (1‐D‐ and 2‐D‐electrophoresesis, Western blot) were applied. The results of the morphological and biochemical investigation proved that this mature male suffered for many years from and probably died of a carcinoma of the prostate. The diagnosis mainly rests on the results of the microscopic examination of the lesions and the positive evidence of PSA, which is an important marker for the diagnosis of prostate cancer. It is remarkable that, in this ancient case, the morphological pattern at the microlevel is the same as in recent cases. The loss of the spongy bone substance (red bone marrow) provoked chronic anemia during the final months of the life of this king. The proteomic techniques applied are new for the investigation of recent and ancient macerated bones. Sensitive and reliable biochemical markers (PSA) are an important precondition to detect such tumors in recent and ancient materials. Currently, this is the oldest known case of prostate cancer diagnosed reliably by morphological and biochemical techniques. © 2007 Wiley‐Liss, Inc.
Akt promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function
Authors: Fraser Michael , Bai Tao , Tsang Benjamin K. 
Published: October 2007

AbstractResistance to cisplatin‐based chemotherapy is a major cause of treatment failure in human ovarian cancer. Wild‐type TP53 status is often, but not always, associated with cisplatin sensitivity, suggesting that additional factors may be involved. Overexpression/activation of the phosphatidylinositol‐3‐kinase/Akt pathway is commonly observed in ovarian cancer, and Akt activation is a determinant of chemoresistance in ovarian cancer cells, an effect that may be due, in part, to its inhibitory actions on p53‐dependent apoptosis. To that end, we examined the role and regulation of p53 in chemosensitive ovarian cancer cells, as well as in their chemoresistant counterparts, and investigated if and how Akt influences this pathway. Cisplatin induced apoptosis in chemosensitive, but not chemoresistant cells, and this was inhibited by downregulation of p53. Cisplatin upregulated PUMA in a p53‐dependent manner, and the presence of PUMA was necessary, but not sufficient for cisplatin‐induced apoptosis. p53 was phosphorylated on numerous N‐terminal residues, including Ser15, Ser20, in response to cisplatin in chemosensitive, but not chemoresistant cells. Furthermore, activation of Akt inhibited the cisplatin‐induced upregulation of PUMA, and suppressed cisplatin‐induced p53 phosphorylation, while inhibition of Akt increased total and phospho‐p53 contents and sensitized p53 wild‐type, chemoresistant cells to cisplatin‐induced apoptosis. Finally, mutation of Ser15 and/or Ser20, but not of Ser37, to alanine significantly attenuated the ability of p53 to facilitate CDDP‐induced apoptosis, and this was independent of PUMA expression. These results support the hypothesis that p53 is a determinant of CDDP sensitivity, and suggest that Akt contributes to chemoresistance, in part, by attenuating p53‐mediated PUMA upregulation and phosphorylation of p53, which are essential, but independent determinants of sensitivity to CDDP‐induced apoptosis. © 2007 Wiley‐Liss, Inc.
Downregulation of IFN‐γR in association with loss of Fas function is linked to tumor progression
Authors: Yang Dafeng , Stewart Trina J. , Smith Kimberly K. , Georgi David , Abrams Scott I. , Liu Kebin 
Published: October 2007

AbstractThe host immune system functions as an intrinsic surveillance network in the recognition and destruction of tumor cells, and it has been demonstrated that lymphocytes and IFN‐γ are the primary tumor suppressors of the immune system. However, the immune system can concurrently select for tumor variants with reduced immunogenicity and aggressive phenotypes. We report here that tumor escape variants that have survived CTL adoptive immunotherapy exhibited decreased expression levels of both Fas and IFN‐γR in vitro. Furthermore, examination of spontaneously arising mouse primary mammary carcinoma and lung metastases revealed that both Fas and IFN‐γR protein levels were dramatically lower in lung metastases than in primary tumors in vivo. Functional disruption of either the Fas‐ or the IFN‐γ signaling pathway enhanced the colonization efficiency of preexisting metastatic tumor cells, whereas disruption of both Fas and IFN‐γR pathways resulted in synergistic augmentation of the colonization efficiency of the preexisting metastatic tumor cells, as determined by experimental lung metastases assay. Gene expression profiling revealed that altered expression of genes involved in immediate IFN‐γR signaling, the interferon primary response, apoptosis and tumor colonization is associated with loss of IFN‐γR function and enhanced metastatic potential. Interestingly, disruption of IFN‐γR function did not alter tumor cell susceptibility to CTL‐mediated cytotoxicity, but is linked to enhanced infiltration of endogenous T cells in the tumor microenvironment in vivo. These findings suggest that coordinate downregulation of Fas and IFN‐γR, 2 key components of cancer immunosurveillance system on tumor cells, leads to a more aggressive metastatic phenotype. © 2007 Wiley‐Liss, Inc.
Retracted: Dose‐dependent dual effect of HTLV‐1 tax oncoprotein on p53‐dependent nucleotide excision repair in human T‐cells
Authors: Schavinsky‐Khrapunsky Yana , Priel Esther , Aboud Mordechai 
Published: October 2007

The above article, published online on 4 October 2007 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 122, pp. 305‐316, has been retracted by agreement between the journal Editor in Chief, Professor Peter Lichter, and John Wiley & Sons Ltd. The retraction has been agreed as the bands in Figs 1, 2, 5 and 6 appear to have been manipulated.Reference

Schavinsky‐Khrapunsky, Y.,
Priel, E. and
Aboud, M. (2008), . J. Cancer, 122: 305–316. doi:10.1002/ijc.23091
Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest
Authors: Kanda Hideki , Ishii Kenichiro , Ogura Yuji , Imamura Tetsuya , Kanai Masahiro , Arima Kiminobu , Sugimura Yoshiki 
Published: October 2007

Abstractα‐1 adrenoceptor antagonists are generally prescribed for benign prostate hyperplasia with lower urinary tract symptoms. Naftopidil, a selective α‐1 adrenoceptor antagonist, is frequently used in Japan because it has fewer side effects. Here we demonstrate for the first time that naftopidil has growth inhibitory effect in androgen‐sensitive and ‐insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 ± 4.0 μM in androgen‐sensitive LNCaP cells and 33.2 ± 1.1 μM in androgen‐insensitive PC‐3 cells. FACS analysis revealed that cell growth inhibition by naftopidil was due to the arrest of the G1 cell cycle. Expressions of p27kip1 and p21cip1 were significantly increased in LNCaP cells treated with naftopidil. In PC‐3 cells, naftopidil induced p21cip1 but not p27kip1. In vivo, oral administration of naftopidil to nude mice inhibited the growth of PC‐3 tumors as compared to vehicle‐treated controls. These results suggest that naftopidil may be useful in the chemoprevention of prostate cancer and the intervention of hormone refractory prostate cancer. © 2007 Wiley‐Liss, Inc.
Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R
Authors: Patel Bhaumik B. , Sengupta Radha , Qazi Sadia , Vachhani Hetal , Yu Yingjie , Rishi Arun K. , Majumdar Adhip P.N. 
Published: October 2007

AbstractCurcumin (diferuloylmethane), which has been shown to inhibit growth of transformed cells, has no discernible toxicity and achieves high levels in colonic mucosa. 5‐fluorouracil (5‐FU) or 5‐FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but with limited success. The present investigation was, therefore, undertaken to examine whether curcumin in combination with conventional chemotherapeutic agent(s)/regimen will be a superior therapeutic strategy for colorectal cancer. Indeed, results of our in vitro studies demonstrated that curcumin together with FOLFOX produced a significantly greater inhibition (p < 0.01) of growth and stimulated apoptosis (p < 0.001) of colon cancer HCT‐116 and HT‐29 cells than that caused by curcumin, 5‐FU, curcumin + 5‐FU or FOLFOX. These changes were associated with decreased expression and activation (tyrosine phosphorylation) of EGFR, HER‐2, HER‐3 (72–100%) and IGF‐1R (67%) as well as their downstream effectors such as Akt and cycloxygenase‐2 (51–97%). Furthermore, while these agents produced a 2–3‐fold increase in the expression of IGF‐binding protein‐3 (IGFBP‐3), curcumin together with FOLFOX caused a 5‐fold increase in the same, when compared to controls. This in turn led to increased sequestration of IGF by IGFBP‐3 rendering IGF‐1 unavailable for binding to and activation of IGF‐1R. We conclude that the superior effects of the combination therapy of curcumin and FOLFOX are due to attenuation of EGFRs and IGF‐1R signaling pathways. We also suggest that inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer. © 2007 Wiley‐Liss, Inc.
The role of insulin‐like growth factor binding protein‐3 in the growth inhibitory actions of androgens in LNCaP human prostate cancer cells
Authors: Peng Lihong , Wang Jining , Malloy Peter J. , Feldman David 
Published: October 2007

AbstractInsulin‐like growth factor binding protein‐3 (IGFBP‐3), an antiproliferative and proapoptotic protein, has been shown to be upregulated by growth inhibitory concentrations of androgens in LNCaP human prostate cancer (PCa) cells, but the mechanism of regulation and the role of IGFBP‐3 in the modulation of PCa cell proliferation are unknown. In this study, we have examined the effects of a range of concentrations of the synthetic androgen R1881 on IGFBP‐3 expression and cell growth in LNCaP cells. We have also investigated the role of androgen‐stimulated IGFBP‐3 in androgen‐induced growth inhibition. We show that low doses of R1881 stimulate LNCaP cell proliferation, but do not induce IGFBP‐3 expression, whereas high doses of R1881 that inhibit cell growth, significantly increase expression of IGFBP‐3. Importantly, we demonstrate that the combination of calcitriol and androgens not only synergistically upregulates IGFBP‐3 expression but also inhibits cell growth better than either hormone alone. siRNA knockdown of IGFBP‐3 expression partially reverses the growth inhibition by calcitriol and by androgens. Furthermore, we find that the growth inhibitory dose of R1881 leads to increases in the cyclin dependent kinase inhibitors (CDKIs), p21 and p27 as well as to G1 arrest. These changes can be blocked or partially reversed by IGFBP‐3 siRNA, indicating that the induction of CDKIs is downstream of IGFBP‐3. Our data suggest, for the first time, that IGFBP‐3 is involved in the antiproliferative action of high doses of androgens partly through p21 and p27 pathways and that IGFBP‐3 may contribute significantly to androgen‐induced changes in LNCaP cell growth. © 2007 Wiley‐Liss, Inc.
EGFR induces expression of IRF‐1 via STAT1 and STAT3 activation leading to growth arrest of human cancer cells
Authors: Andersen Peter , Pedersen Mikkel Wandahl , Woetmann Anders , Villingshøj Mette , Stockhausen Marie‐Thérése , Ødum Niels , Poulsen Hans Skovgaard 
Published: October 2007

AbstractRecently, we reported that epidermal growth factor receptor (EGFR) induce expression of a module of genes known to be inducible by interferons and particularly interferon‐γ. Here we show that the module is tightly regulated by EGFR in the 2 human cancer cell lines that overexpress EGFR, A431 and HN5. The module of genes included the tumor suppressor IRF‐1, which was used as a prototypical member to further investigate the regulation and function of the module. Ligand‐activated EGFR induce expression of IRF‐1 via phosphorylation of STAT1 and STAT3. In contrast, cells expressing the constitutively active cancer specific receptor EGFRvIII are unable to mediate phosphorylation of these STATs and thereby incapable of inducing IRF‐1. We also demonstrate that IRF‐1 is expressed in an EGF dose‐dependent manner, which correlates with inhibition of cell proliferation, and that the regulation of IRF‐1 is partially dependent on intracellular Src family kinase activity. Treatment with the dual specific Abl/c‐Src kinase inhibitor AZD0530 significantly reduces the growth inhibitory effect of high EGF concentrations, signifying that EGFR induced IRF‐1 is responsible for the observed growth inhibition. In addition, we show that media from these EGF treated cancer cells upregulate the activation marker CD69 on both B‐cells and T‐cells in peripheral blood. Taken together, these results suggest that cells acquiring sustained high activity of oncogenes such as EGFR are able to activate genes, whose products mediate growth arrest and activate immune effector cells, and which potentially could be involved in alerting the immune system in vivo leading to elimination of the transformed cells. © 2007 Wiley‐Liss, Inc.
Identification of parameters in normal error component logit‐mixture (NECLM) models
Authors: Walker Joan L. , Ben‐Akiva Moshe , Bolduc Denis 
Published: October 2007

AbstractAlthough the basic structure of logit‐mixture models is well understood, important identification and normalization issues often get overlooked. This paper addresses issues related to the identification of parameters in logit‐mixture models containing normally distributed error components associated with alternatives or nests of alternatives (normal error component logit mixture, or NECLM, models). NECLM models include special cases such as unrestricted, fixed covariance matrices; alternative‐specific variances; nesting and cross‐nesting structures; and some applications to panel data. A general framework is presented for determining which parameters are identified as well as what normalization to impose when specifying NECLM models. It is generally necessary to specify and estimate NECLM models at the levels, or structural, form. This precludes working with utility differences, which would otherwise greatly simplify the identification and normalization process. Our results show that identification is not always intuitive; for example, normalization issues present in logit‐mixture models are not present in analogous probit models. To identify and properly normalize the NECLM, we introduce the ‘equality condition’, an addition to the standard order and rank conditions. The identifying conditions are worked through for a number of special cases, and our findings are demonstrated with empirical examples using both synthetic and real data. Copyright © 2007 John Wiley & Sons, Ltd.
On the intra‐annual variability of atmospheric circulation in the Mediterranean region
Authors: Lolis C. J. , Metaxas D. A. , Bartzokas A. 
Published: October 2007

AbstractSome aspects on the intra‐annual variability and the seasonal peculiarities of the atmospheric circulation in the Mediterranean region are examined. T‐mode factor analysis is applied on the long‐term (1948–2003) 5‐day mean values of relative geostrophic vorticity for the 73 5‐day periods of the year. The analysis is applied for sea‐surface and 500‐hPa levels. For sea level, two circulation types are found to be dominant: the type of the warm period and the type of the cold period, characterizing the so‐called Mediterranean climate; they are strongly dependent on the thermal and humidity characteristics of the earth's surface and the position and strength of the sub‐tropical (Azores) anti‐cyclone. For 500‐hPa level, two extra but weaker circulation types are added, prevailing mainly during the transitional seasons and modifying the smooth intra‐annual variation of the atmospheric circulation. In this case, the thermal influence of the earth's surface appears to be weaker, while other circulation features, such as blocking activity and/or cut‐off lows, seem to play an important role too. Copyright © 2007 Royal Meteorological Society
Expression of nuclear notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated Akt
Authors: Doucas Helena , Mann Christopher D. , Sutton Christopher D. , Garcea Guiseppe , Neal Christopher P. , Berry David P. , Manson Margaret M. 
Published: October 2007

AbstractBackground and ObjectivesReactivation of the Notch signalling pathway occurs in a range of human malignancies. Previous research suggests that Notch3 is expressed in pancreatic adenocarcinomas, but neither cellular location nor association with clinical parameters has been described. The relationship between Notch3, clinical endpoints, and other proteins with potential to interact with Notch was therefore examined.MethodsAn immunohistochemical study was performed on human pancreatic adenocarcinoma (n = 23) and normal pancreas (n = 12), to assess expression of Notch3, cyclin D1, pAkt, STAT3 and pSTAT3. Immunohistochemical data were then correlated with clinicopathological characteristics.ResultsNotch3 was significantly overexpressed in the cytoplasm of 73.9% of tumours. Nuclear expression was not observed in normal pancreatic ductal tissue, but was noted in 43.5% of tumours. No tumour expressing nuclear Notch3 was resectable. There were significant correlations between expression and intracellular location of Notch3 and each of STAT3, pSTAT3 and pAkt, but not cyclin D1.ConclusionThe presence of Notch3 in tumour nuclei is likely to represent functional activation of the protein, and is clearly linked to a more aggressive tumour phenotype. The correlation with STAT3, pSTAT3 and pAkt expression has not previously been described and the concurrent intracellular localisation of these proteins suggests a functional relationship between them. J. Surg. Oncol. 2008;97:63–68. © 2007 Wiley‐Liss, Inc.
Breast cancer screening compliance among young women in a free access healthcare system
Authors: Amin Asna , Shriver Craig D. , Henry Leonard R. , Lenington Sarah , Peoples George E. , Stojadinovic Alexander 
Published: October 2007

AbstractBackground and ObjectivesTo examine mammographic screening compliance among young military healthcare beneficiaries and to examine factors related to one time and recent mammographic compliance.MethodsMedical records were reviewed for 1,073 subjects (age 41–47) recording dates of the two most recent screening mammograms. Examined outcomes were: whether the woman ever had mammography and, if so, whether she had a mammogram within 400 days. Examined predictors were: ethnicity, age, Gail Model risk score, family history, whether the woman knew a young woman with breast cancer, and importance attributed to breast cancer screening.Results90.4% of women studied had at least one mammogram. 71.1% underwent screening within 400 days. Rates of ever having mammography were higher for women with family history of breast cancer and Asian, Pacific Islander, Black or Hispanic women. No measured covariate correlated with having mammography within 400 days.ConclusionsOne time screening participation was high in this select group of women for whom cost and access barriers were removed, but was lower with regard to having a recent mammogram. Correlates of ever having and recent mammography are not synonymous. J. Surg. Oncol. 2008;97:20–24. © 2007 Wiley‐Liss, Inc.
The value of expert second opinion in diagnosis of soft tissue sarcomas
Authors: Lehnhardt Marcus , Daigeler Adrien , Hauser Joerg , Puls Alexander , Soimaru Christian , Kuhnen Cornelius , Steinau Hans Ulrich 
Published: October 2007

AbstractIntroductionSoft tissue sarcomas represent a heterogenous group of tumours with a wide range of clinical behaviour. Exact determination of diagnosis and prognosis is critical in order to guide surgical decisions and provide systemic therapy or radiation for patients. The value of consultative second opinions has been proven for general surgical pathology; some studies suggest an even higher value for the soft tissue tumour specimens in particular.MethodsWe reviewed 603 patients who were operated on at our institution with the diagnosis of soft tissue sarcoma and aggressive fibromatosis; we focused on mismatches in primary and definite tumour‐entity and ‐grading with respect to the diagnosing institution and the primary surgical procedure.ResultsWe found concordant primary diagnosis in 28.3% for pathologists in private clinics, 29.6% for hospital pathologists, 36.8% for academic medical centres (university hospitals) and 70.5% for the Department of Pathology at our institution. An improvement in diagnosis or confirmation of the correct primary diagnosis by the second opinion was seen in 73.1% of the patients; in 2.5%, the second opinion was false.DiscussionFor accurate determination of prognosis and to provide optimal therapeutic decisions we consider expert second opinion essential for optimal treatment of soft tissue sarcomas. J. Surg. Oncol. 2008;97:40–43. © 2007 Wiley‐Liss, Inc.
Curing hepatocellular carcinomatosis with biologic therapy and surgery: Achieving the impossible?
Authors: Thomas Melanie B. , Tetzlaff Eric , Lozano Richard , Samp Leigh , Butler Charles E. , Gannon Christopher , Hamilton Stanley , Vauthey Jean Nicholas , Abdalla Eddie 
Published: October 2007

AbstractHepatocellular carcinoma (HCC) that present as hemoperitoneum are uncommon, often recur as peritoneal carcinomatosis, and have poor prognosis. Systemic chemotherapies are minimally effective in advanced HCC and less so as neo‐adjuvant therapy. This report describes a 47‐year woman with ruptured HCC who developed recurrent carcinomatosis. She received biologically targeted systemic therapy which resulted in significant radiographic tumor response. Salvage surgery revealed complete pathologic response in all tumor nodules, thus the patient was rendered cancer‐free. J. Surg. Oncol. 2008;97:82–84. © 2007 Wiley‐Liss, Inc.
p53 Codon 72 polymorphism and the risk of esophageal squamous cell carcinoma
Authors: Yang Wenjun , Zhang Yanyan , Tian Xiuyun , Ning Tao , Ke Yang 
Published: October 2007

AbstractThe polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous malignant tumors, particularly carcinomas associated with human papillomavirus (HPV) infection. However, the results remain controversial. To address a potential correlation between the p53 genotypes and the risk of esophageal squamous cell carcinoma (ESCC), we investigated the p53 codon 72 polymorphism in 435 patients with ESCC and 550 cancer‐free subjects from the same geographical region. p53 Arg/Arg genotype was significantly increased in ESCC cases compared with control subjects (85.7 vs. 49.6%, P < 0.001), resulting in an elevated ESCC risk (OR = 6.48, 95% CI = 4.65–9.03). In addition, among p53 Arg/Arg carriers, HPV infection, smoking, and drinking might further increase the risk of ESCC development. © 2007 Wiley‐Liss, Inc.