bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Vascular Endothelial Growth Factor-C and -D Expression in Human Pancreatic Cancer
Authors: Kurahara Hiroshi , Takao Sonshin , Maemura Kousei , Shinchi Hiroyuki , Natsugoe Shoji , Aikou Takashi 
Published: September 2005

Abstract
Purpose: The aim of this study was to evaluate the expression of vascular endothelial growth factor (VEGF)-C and -D in pancreatic cancer and to reveal its relation to lymph node metastasis.
Experimental Design: Formalin-fixed, paraffin-embedded blocks were obtained from 58 patients with pancreatic head cancer. All of the patients underwent a curative resection. The total number of resected lymph nodes was 1,058. The expressions of VEGF-C and -D were evaluated by immunohistochemical staining. To evaluate the relation to lymph node metastasis, the expressions of VEGF-C and -D between the marginal and central portions in the tumor were compared. When &gt;25% of the tumor cells showed distinct staining, the portion was judged as high expression.
Results: The two groups with high expression of VEGF-C (P = 0.015) and VEGF-D (P = 0.020) in the marginal portion had a significantly higher incidence of lymph node metastasis compared with the groups with low expression, respectively. Furthermore, the group with high expression of both VEGF-C and -D in the marginal portion had a higher incidence of lymph node metastasis compared with the group with low expression (P = 0.007). The 5-year survival rate of patients with high expression of both VEGF-C and -D in the marginal portion was significantly lower than that of patients with low expression of both VEGF-C and -D (P = 0.017).
Conclusions: VEGF-C and -D expression in tumor cells in the marginal portion of the tumor significantly associated with lymphatic metastasis and prognosis in patients with pancreatic head cancer.
Androgen Receptor Is Targeted to Distinct Subcellular Compartments in Response to Different Therapeutic Antiandrogens
Authors: Whitaker Hayley C. , Hanrahan Sarah , Totty Nick , Gamble Simon C. , Waxman Jonathan , Cato Andrew C. B. , Hurst Helen C. , Bevan Charlotte L. 
Published: September 2005

Abstract
Purpose: Antiandrogens are routinely used in the treatment of prostate cancer. Although they are known to prevent activation of the androgen receptor (AR), little is known about the mechanisms involved. This report represents the first study of the localization of wild-type AR following expression at physiologic relevant levels in prostate cells and treatment with androgen and antiandrogens.
Experimental Design: We have characterized a cellular model for prostate cancer using in situ cellular fractionation, proteomics, and confocal microscopy and investigated the effect of antiandrogens in clinical use on the subcellular localization of the AR.
Results: Different antiandrogens have diverse effects on the subcellular localization of the AR. Treatment with androgen results in translocation from the cytoplasm to the nucleoplasm, whereas the antiandrogens hydroxyflutamide and bicalutamide lead to reversible association with the nuclear matrix. In contrast, treatment with the antiandrogen cyproterone acetate results in AR association with cytoplasmic membranes and irreversible retention within the cytoplasm. In addition, we demonstrate that AR translocation requires ATP and the cytoskeleton, regardless of ligand.
Conclusions: These results reveal that not all antiandrogens work via the same mechanism and suggest that an informed sequential treatment regime may benefit prostate cancer patients. The observed subnuclear and subcytoplasmic associations of the AR suggest new areas of study to investigate the role of the AR in the response and resistance of prostate cancer to antiandrogen therapy.
A Clinicobiological Model Predicting Survival in Medulloblastoma
Authors: Ray Amit , Ho Michael , Ma Jing , Parkes Robert K. , Mainprize Todd G. , Ueda Shigeo , McLaughlin John , Bouffet Eric , Rutka James T. , Hawkins Cynthia E. 
Published: September 2005

AbstractPurpose: The purpose of this study was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB).Experimental Design: Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples. The arrays were assayed for immunohistochemical expression of MYC, p53, platelet-derived growth factor receptor-α, ErbB2, MIB-1, and TrkC and for apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival, a weighted predictive score was calculated based on their hazard ratios (HRs). The sum of these scores was then used to give an overall prediction of survival using a nomogram.Results: The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR, 2.02; P = 0.01) and p53 (HR, 2.29; P = 0.02), TrkC (HR, 0.65; P = 0.14), and ErbB2 (HR, 1.51; P = 0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these HRs. The 5-year survival rate for patients at the 10th, 50th, and 90th percentiles of the score distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy.Conclusions: In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately and establishes a framework for comparing prognostic markers in future clinical studies.
Effects of Exemestane and Tamoxifen in a Postmenopausal Breast Cancer Model
Authors: Jelovac Danijela , Macedo Luciana , Handratta Venkatesh , Long Brian J. , Goloubeva Olga G. , Ingle James N. , Brodie Angela M. H. 
Published: September 2005

Abstract
Purpose: To optimize treatment strategies for postmenopausal breast cancer patients, we investigated the efficacy of the steroidal aromatase inhibitor exemestane alone or in combination with the antiestrogen tamoxifen in a xenograft model of postmenopausal breast cancer. We also determined the effects of these agents in sequential second-line therapy and the effect of the nonsteroidal aromatase inhibitor letrozole on tumors that progressed on the above treatments.
Experimental: Aromatase-transfected human estrogen receptor-positive breast cancer cells (MCF-7Ca) were grown as tumors in ovariectomized athymic mice. Animals received subcutaneous injection with vehicle, tamoxifen, exemestane, tamoxifen plus exemestane, and letrozole. Tumor volumes were measured weekly.
Results: All treatments were effective initially in suppressing tumor growth as first-line therapy compared with vehicle treatment. Exemestane suppressed tumor growth to a greater extent than tamoxifen. However, the combination of tamoxifen plus exemestane was more effective than either drug alone. After tumor volumes doubled on initial treatment, the mice were crossed over to receive exemestane or tamoxifen. Tumor growth slowed briefly in mice treated with tamoxifen and crossed over to exemestane, but tumor growth continued unabated in those changed from exemestane to tamoxifen. However, letrozole was effective in both groups as third-line therapy for a limited period. Letrozole as initial single agent was the best overall treatment in terms of the degree of tumor suppression and the length of effectiveness of treatment.
Conclusion: Exemestane was more effective in controlling tumor growth than tamoxifen. In addition, the combination of exemestane plus tamoxifen was clearly more effective than sequential use of these agents in the tumor model. However, the nonsteroidal aromatase inhibitor letrozole as first-line therapy was overall the most effective treatment in controlling tumor growth.
Differences in Prognostic Molecular Markers between Women Over and Under 45 Years of Age with Advanced Ovarian Cancer
Authors: Chan John K. , Loizzi Vera , Magistris Alessandra , Lin Fritz , Rutgers Joanne , Osann Kathryn , DiSaia Philip J. , Berman Michael L. 
Published: September 2005

Abstract
Purpose: The purpose of this study was to determine whether differences in molecular markers might explain the better prognosis of women ≤45 years of age versus women &gt;45 years of age diagnosed with ovarian cancers.
Experimental Design: Tissue sections from women with stage III–IV ovarian cancers were examined for expression of CD34, p53, and HER2. The Kaplan-Meier method and Cox Proportional Hazard analyses were used to identify predictors for outcome.
Results: Fifty-two women ≤45 years of age were matched with 52 women who were &gt;45 years old. Of the 46 available tissue sections, 24 were from the younger age group (mean age, 41 years), and 22 were from the older age group (mean age, 61 years). Based on CD34 expression, tumors from women &gt;45 years of age had lower microvessel density (MVD) compared with tumors of younger women (10.3 versus 16.1 microvessels per ×400 field; P = 0.03). Lower MVD (≤11 microvessels per ×400 field) predicted for a worse prognosis than higher MVD (&gt;11 microvessels per ×400 field) in the overall study group (P = 0.001) and within the older subgroup (P = 0.03). The expressions of p53 (P = 0.13) and HER2 (P = 0.49) did not vary between the two age groups. The median survivals of those with tumors that overexpressed p53 and HER2 were 28.6 and 23.9 months compared with 51.7 and 38.6 months in those with cancers that underexpressed these markers, respectively (P = 0.09 for p53, P = 0.15 for HER2).
Conclusions: Ovarian cancers in women &gt;45 years of age had lower MVD compared with those in women ≤45 years of age. Lower MVD was an independent prognostic factor for decreased survival. Lower frequency of neovascularization in these cancers may contribute to the decreased survival observed in women &gt;45 years of age.
Carbonic Anhydrase IX in Early-Stage Non–Small Cell Lung Cancer
Authors: Kim Seok Jin , Rabbani Zahid N. , Vollmer Robin T. , Schreiber Ernst-Gilbert , Oosterwijk Egbert , Dewhirst Mark W. , Vujaskovic Zeljko , Kelley Michael J. 
Published: September 2005

AbstractPurpose: Tumor hypoxia is associated with poor prognosis and increased tumor aggressiveness. Carbonic anhydrase (CA) IX, an endogenous marker for tumor hypoxia, catalyzes the hydration of carbon dioxide into carbonic acid and contributes to the pH regulation of tumor cells. Therefore, CA IX might allow tumors to acclimate to a hypoxic microenvironment, promoting tumor cell proliferation. We hypothesized that CA IX expression is related to tumor cell proliferation and poor disease-free survival in patients with early-stage non–small-cell lung cancer (NSCLC).Experimental Design: CA IX expression was measured in 75 resected NSCLC tumors to assess prognostic implications for disease-free survival. The relationship of CA IX expression with microvessel density (MVD) and proliferation (Ki-67) index was assessed via colocalization analysis.Results: All patients had operable NSCLC (stage I, 58; stage II, 17). CA IX expression was present in 54 (72%) of 75 patients and was associated with tumor necrosis (P &lt; 0.05). CA IX-positive tumor areas showed greater cell proliferation as measured by Ki-67 index (P &lt; 0.05) and less MVD (P &lt; 0.05) than did CA IX-negative areas in colocalization analysis. The percentage of CA IX-positive tumor cells was significantly related to postoperative recurrence and poor disease-free survival (P &lt; 0.05). Ki-67 index and pathologic stage were also independent prognostic factors for worse disease-free survival (P &lt; 0.05).Conclusions: CA IX expression of tumor cells may be an indicator for poor disease-free survival in early-stage NSCLC.
Cyclooxygenase-2 Expression
Authors: Soumaoro Labile Togba , Uetake Hiroyuki , Higuchi Tetsuro , Takagi Yoko , Enomoto Masayuki , Sugihara Kenichi 
Published: September 2005

Abstract
Purpose: Recent studies have shown that cyclooxygenase (Cox)-2 may be involved in colorectal carcinogenesis. We aimed to determine whether Cox-2 expression in itself can predict outcome of colorectal cancer patient after surgery. In addition, the expression of Cox-1 was also evaluated.
Experimental Design: Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox-2 and Cox-1 expressions. The specimens were graded based on the intensity and extent of staining; then, the correlations between Cox-2 and Cox-1 expressions with clinicopathologic parameters and survival time were analyzed.
Results: Expression of Cox-2 was positive in 70.8% of primary tumor, 92.0% of lymph node metastases, 100.0% of hepatic metastases, and was significantly associated with tumor size, depth of invasion, lymph node metastasis, vessels invasion, stage and recurrence. In contrast, Cox-1 was positive in 42.7% of primary tumor, 84.0% of lymph node metastases, 37.5% hepatic metastases, and was associated with only tumor size. Patients with Cox-2–positive tumors had a significant shorter survival time than those with negative tumors did (P = 0.0006 by log-rank test); and, in a multivariate analysis, Cox-2 was an independent prognostic factor (P = 0.0103; relative risk 4.114; 95% confidence interval, 1.397–12.120). Cox-1 status had no statistically effect on patient survival time.
Conclusions: Elevated Cox-2 expression, but not that of Cox-1, was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients.
Correlation of Molecular Genetics with Molecular and Morphological Imaging in Gliomas with an Oligodendroglial Component
Authors: Walker Carol , du Plessis Daniel G. , Fildes Diane , Haylock Brian , Husband David , Jenkinson Michael D. , Joyce Kathy A. , Broome John , Kopitski Klaus , Prosser Joanne , Smith Trevor , Vinjamuri Sobhan , Warnke Peter C. 
Published: September 2005

Abstract
Purpose: Since the recognition that oligodendrogliomas may be chemosensitive, their diagnosis and clinical management has become highly controversial. Histopathology diagnosis remains challenging and new tools such as molecular genetics or molecular imaging require evaluation.
Experimental Design: In a single-center, population-based prospective study, allelic imbalance in chromosomes 1p36, 19q13, 17p13, 10p12–15, and 10q22–26 has been investigated in 19 oligodendroglioma WHO grade 2 (OII), 20 oligoastrocytoma WHO grade 2 (OAII), 8 oligodendroglioma WHO grade 3 (OIII), and 12 oligoastrocytoma WHO grade 3 (OAIII), and compared with pretherapy histopathology, computed tomography and/or magnetic resonance (CT and/or MR), [fluorine-18]fluoro-2-deoxyglucose (18F-FDG), and thallium-201 single-photon emission computed tomography (201Tl SPECT).
Results: In 50 cases, 18F-FDG uptake correlated with 201Tl uptake; however, 8 cases had increased 201Tl uptake but were hypometabolic for 18F-FDG, and 1 case was hypermetabolic with normal 201Tl uptake. Sixteen cases enhanced on CT/MR but failed to show 201Tl uptake; and 2 low-grade non-enhancing oligodendrogliomas had increased 201Tl uptake. Increased metabolism was more likely in high-grade cases, with 201Tl uptake more strongly correlated with grade than was 18F-FDG uptake. Tumors with 1p/19q loss were more likely to show increased 201Tl uptake and, to a lesser degree, increased 18F-FDG uptake than those without these losses. Elevated metabolism in 28% of low-grade tumors was significantly more common in tumors with 1p/19q loss, and increased uptake of both 18F-FDG and 201Tl in low-grade cases was found only in those with 1p/19q loss.
Conclusions: In this study, dissociation of uptake of contrast agents and radiotracers suggests independent deregulation of the blood–brain barrier breakdown and metabolism during disease progression of oligodendroglial neoplasms, and the association of elevated metabolism with 1p/19q loss, particularly in low-grade tumors, may have implications for clinical management.
Dendritic Cell Infiltration and Prognosis of Early Stage Breast Cancer
Authors: Treilleux Isabelle , Blay Jean-Yves , Bendriss-Vermare Nathalie , Ray-Coquard Isabelle , Bachelot Thomas , Guastalla Jean-Paul , Bremond Alain , Goddard Sophie , Pin Jean-Jacques , Barthelemy-Dubois Clarisse , Lebecque Serge 
Published: September 2005

Abstract
Purpose: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome.
Experimental Design: T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series.
Results: Infiltration by immature CD207/Langerin+ DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients.
Conclusions: Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.
OCT4
Authors: Jones Timothy D. , Ulbright Thomas M. , Eble John N. , Cheng Liang 
Published: September 2005

AbstractPurpose: OCT4 (POU5F1, OCT3) immunostaining highlights pluripotent cells (embryonal carcinoma and seminoma) in primary testicular germ cell tumors, but its relative usefulness in diagnosing intratubular germ cell neoplasia, unclassified (IGCNU) is not well established. The present study aimed to establish OCT4 as a sensitive and specific maker for IGCNU, a putative precursor for adult germ cell tumors.Experimental Design: We evaluated OCT4 immunostaining in 44 cases of IGCNU from patients who had testicular germ cell tumors. In addition, 27 of the 44 IGCNU sections were also examined with antibodies to placenta-like alkaline phosphatase, the most frequently used immunohistochemical marker for intratubular germ cell neoplasia. Sections from the testes of 10 patients who had undergone orchiectomy for hormonal treatment of prostate cancer and from autopsies of 10 patients without histories of germ cell tumors were also examined for OCT4 immunostaining. The immunoreactivity of the autopsy tissues was determined with vimentin staining, and all were reactive.Results: In all 44 of the cases, antibody to OCT4 marked the nuclei of nearly all of the dysplastic cells of intratubular germ cell neoplasia but not non-neoplastic testicular cells. The staining intensity was strong in every case, and there was little or no background staining. All 20 of the control specimens (10 orchiectomy specimens from prostate cancer patients and 10 testes from autopsies) were completely negative for OCT4. The 27 cases that were stained with antiplacenta-like alkaline phosphatase antibodies showed staining of variable intensity in the areas of intratubular germ cell neoplasia, and there was a high level of background staining artifact.Conclusions: OCT4 is a sensitive and specific maker for intratubular germ cell neoplasia.
Molecular Stratification of Diagnostically Challenging High-Grade Gliomas Composed of Small Cells
Authors: Korshunov Andrey , Sycheva Regina , Golanov Andrey 
Published: September 2005

Abstract
Purpose: There is considerable morphologic overlap between various entities of high-grade gliomas, and, therefore, a further planning of their optimal treatment is a controversial issue. The aim of this study was molecular stratification of morphologically ambiguous high-grade gliomas composed from small cells. Fluorescence in situ hybridization (FISH) with commercially available probes was used for this purpose.
Experimental Design: We analyzed a set of 114 high-grade small-cell gliomas that were difficult to interpret diagnostically because of their distinct cytological origin. FISH assay with locus probes for EGFR, p16, PTEN, and 1p and 19q was done.
Results: Morphologically uniform high-grade gliomas composed of small cells varied greatly in terms of molecular features and clinical outcome. Four clinically relevant subsets of patients whose tumors showed distinctly different molecular profiles were identified as follows: (a) 13 patients whose tumors exhibited no discernable molecular alterations (5-year survival rate, 83%); (b) 20 patients whose tumors harbored either 1p/19q codeletion or isolated deletion of 19q unaccompanied by other molecular abnormalities (5-year survival rate, 59%); (c) 35 patients whose tumors showed p16 and/or PTEN deletions unaccompanied by EGFR amplification (5-year survival rate, 8%); and (d) 46 patients whose tumors harbored EGFR amplification (5-year survival rate, 0).
Conclusions: The FISH method provides clinically useful information in the molecular analysis of morphologically ambiguous malignant small-cell gliomas that could potentially enhance the quality of patient care.