bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noscapine Crosses the Blood-Brain Barrier and Inhibits Glioblastoma Growth
Authors: Landen Jaren W. , Hau Vincent , Wang Mingshen , Davis Thomas , Ciliax Brian , Wainer Bruce H. , Van Meir Erwin G. , Glass Johnathan D. , Joshi Harish C. , Archer David R. 
Published: September 2005

AbstractThe opium alkaloid noscapine is a commonly used antitussive agent available in Europe, Asia, and South America. Although the mechanism by which it suppresses coughing is currently unknown, it is presumed to involve the central nervous system. In addition to its antitussive action, noscapine also binds to tubulin and alters microtubule dynamics in vitro and in vivo. In this study, we show that noscapine inhibits the proliferation of rat C6 glioma cells in vitro (IC50 = 100 μm) and effectively crosses the blood-brain barrier at rates similar to the ones found for agents such as morphine and [Met]enkephalin that have potent central nervous system activity (P ≤ 0.05). Daily oral noscapine treatment (300 mg/kg) administered to immunodeficient mice having stereotactically implanted rat C6 glioblasoma into the striatum revealed a significant reduction of tumor volume (P ≤ 0.05). This was achieved with no identifiable toxicity to the duodenum, spleen, liver, or hematopoietic cells as determined by pathological microscopic examination of these tissues and flow cytometry. Furthermore, noscapine treatment resulted in little evidence of toxicity to dorsal root ganglia cultures as measured by inhibition of neurite outgrowth and yielded no evidence of peripheral neuropathy in animals. However, evidence of vasodilation was observed in noscapine-treated brain tissue. These unique properties of noscapine, including its ability to cross the blood-brain barrier, interfere with microtubule dynamics, arrest tumor cell division, reduce tumor growth, and minimally affect other dividing tissues and peripheral nerves, warrant additional investigation of its therapeutic potential.
Chemotherapy Is More Effective in Patients with Breast Cancer Not Expressing Steroid Hormone Receptors
Authors: Colleoni Marco , Viale Giuseppe , Zahrieh David , Pruneri Giancarlo , Gentilini Oreste , Veronesi Paolo , Gelber Richard D. , Curigliano Giuseppe , Torrisi Rosalba , Luini Alberto , Intra Mattia , Galimberti Viviana , Renne Giuseppe , Nolè Franco , Peruzzotti Giulia , Goldhirsch Aron 
Published: September 2005

Abstract
Purpose: The purpose of this research was to identify factors predicting response to preoperative chemotherapy.
Experimental Design: In a large volume laboratory using standard immunohistochemical methods, we reviewed the pretreatment biopsies and histologic specimens at final surgery of 399 patients with large or locally advanced breast cancer (cT2-T4, N0–2, M0) who were treated with preoperative chemotherapy. The incidence of pathological complete remission and the incidence of node-negative status at final surgery were assessed with respect to initial pathological and clinical findings. Menopausal status, estrogen receptor status, progesterone receptor status [absent (0% of the cells positive) versus expressed], clinical tumor size, histologic grade, Ki-67, Her-2/neu expression, and type and route of chemotherapy were considered.
Results: High rates of pathological complete remission were associated with absence of estrogen receptor and progesterone receptor expression (P &lt; 0.0001), and grade 3 (P = 0.001). Significant predictors of node-negative status at surgery were absence of estrogen receptor and progesterone receptor expression (P &lt; 0.0001), clinical tumor size &lt;5 cm (P &lt; 0.001), and use of infusional regimens (P = 0.003). The chance of obtaining pathological complete remission or node-negative status for patients with endocrine nonresponsive tumors compared with those having some estrogen receptor or progesterone receptor expression was 4.22 (95% confidence interval, 2.20–8.09, 33.3% versus 7.5%) and 3.47 (95% confidence interval, 2.09–5.76, 42.9% versus 21.7%), respectively. Despite the significantly higher incidence of pathological complete remission and node-negative status achieved by preoperative chemotherapy for patients with estrogen receptor and progesterone receptor absent disease, the disease-free survival was significantly worse for this cohort compared with the low/positive expression cohort (4-year disease-free survival %: 41% versus 74%; hazard ratio 3.22; 95% confidence interval, 2.28–4.54; P &lt; 0.0001).
Conclusions: Response to preoperative chemotherapy is significantly higher for patients with endocrine nonresponsive tumors. New chemotherapy regimens or combinations should be explored in this cohort of patients with poor outcome. For patients with endocrine responsive disease, the role of preoperative endocrine therapies should be studied.
Up-Regulation of Functional Chemokine Receptor CCR3 in Human Renal Cell Carcinoma
Authors: Jöhrer Karin , Zelle-Rieser Claudia , Perathoner Alexander , Moser Patrizia , Hager Martina , Ramoner Reinhold , Gander Hubert , Höltl Lorenz , Bartsch Georg , Greil Richard , Thurnher Martin 
Published: September 2005

Abstract
There is increasing evidence that chemokines and chemokine receptors are causally involved in tumorigenesis by facilitating tumor proliferation and metastasis. Little is known about the possible function of chemokine receptors in the development and progression of renal cell carcinoma (RCC). We, therefore, analyzed the expression of chemokine receptors in tumor specimens and adjacent healthy kidney tissues [normal kidney cell (NKC)] from 10 RCC patients. We also characterized the permanent RCC cell line A-498. CCR6, CXCR2, and CXCR3 were consistently expressed by both malignant cells and NKCs. A-498 displayed additional expression of CXCR4. Importantly, the expression of CCR3 was almost absent on NKCs but clearly enhanced in a substantial proportion of RCC specimens. The primary CCR3 ligand, eotaxin-1/CCL11, induced intracellular Ca2+ mobilization, receptor internalization, and proliferation in A-498 cells confirming signaling competence of RCC-associated CCR3. In addition, we screened tumor tissue sections of 219 patients and found that 28% (62 of 219) expressed the CCR3 receptor. The presence of CCR3 in tumor samples seemed to correlate with the grade of malignancy. Previous work has established that eotaxin-1 expression is induced by tumor necrosis factor-α, a cytokine known to be present in RCC tissue. Our data, therefore, supports a scenario in which eotaxin-1 as part of tumor-associated inflammation promotes progression and dissemination of CCR3-positive RCC.
Vaccination with Ep-CAM Protein or Anti-Idiotypic Antibody Induces Th1-Biased Response against MHC Class I- and II-Restricted Ep-CAM Epitopes in Colorectal Carcinoma Patients
Authors: Mosolits Szilvia , Markovic Katja , Frödin Jan-Erik , Virving Lena , Magnusson Carl G. M. , Steinitz Michael , Fagerberg Jan , Mellstedt Håkan 
Published: September 2005

AbstractPurpose: The tumor-associated antigen Ep-CAM (epithelial cell adhesion molecule) is overexpressed in colorectal carcinoma (CRC). The aim of the present study was to evaluate and compare the safety and immunogenicity of a recombinant Ep-CAM protein and a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM.Experimental Design: Patients with resected American Joint Committee on Cancer stages II–IV CRC without remaining macroscopic disease received intradermal/subcutaneous injections of Ep-CAM (400 μg/dose; n = 7) or anti-Id (500 μg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 μg/day, for 4 consecutive days).Results: Adverse reactions were mild (grade I–II). All patients immunized with the Ep-CAM protein produced Ep-CAM–specific IgG antibodies, predominantly IgG1 and IgG3 subclasses, whereas no humoral response was induced by the anti-Id vaccine. All patients, with one exception in each group, mounted an Ep-CAM–specific proliferative T-cell response. The immune response was more rapid, potent, and protracted after Ep-CAM in comparison with anti-Id vaccination. Interferon-γ-secreting cells (ELISPOT) were detected in both immunization groups against the Ep-CAM protein as well as various Ep-CAM–derived MHC class I- and II-restricted peptides. Flow cytometry analysis showed that Ep-CAM–specific interferon-γ- and perforin-producing cells predominantly resided within CD8+CD56− and CD8dimCD56+ T cells.Conclusions: Ep-CAM protein in combination with granulocyte macrophage colony-stimulating factor induced a long-lasting, Th1-biased humoral and cellular immune response compared with anti-Id. Ep-CAM–specific T cells and natural killer-like T cells responding in a MHC class I- and II-restricted manner were also induced. Vaccination with Ep-CAM protein may warrant further investigation as a novel therapeutic approach to CRC.
Effects of the Steroidal Aromatase Inhibitor Exemestane and the Nonsteroidal Aromatase Inhibitor Letrozole on Bone and Lipid Metabolism in Ovariectomized Rats
Authors: Goss Paul E. , Qi Shangle , Cheung Angela M. , Hu Haiqing , Mendes Maria , Pritzker Kenneth P. H. 
Published: September 2005

Abstract
Purpose: Exemestane (EXE) and letrozole (LET) are third-generation aromatase inhibitors currently prescribed for postmenopausal hormone-dependent breast cancer. The impact on end organs of estrogen depletion in menopausal women is of significant clinical importance. We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats.
Experimental Design: OVX rats were treated by weekly intramuscular injection for 16 weeks with 20, 50, and 100 mg/kg EXE, 20 mg/kg 17-H-EXE, and daily oral gavage of 1 mg/kg LET. At the end of the treatment period, bone mineral density (BMD), the bone resorption marker serum pyridinoline, the bone formation marker serum osteocalcin, bone mechanical properties, histomorphometry, and serum lipid concentrations were determined.
Results: Lumbar vertebral and femoral BMD, bending strength of the femur, compressive strength of the fifth lumbar vertebra, and trabecular bone volume were significantly higher in OVX animals given EXE and 17-H-EXE than in OVX controls. EXE and 17-H-EXE significantly reduced an ovariectomy-induced increase in serum pyridinoline and serum osteocalcin. EXE and 17-H-EXE given to OVX rats caused significant reductions of serum cholesterol and low-density lipoprotein cholesterol. In contrast, OVX rats treated with LET had BMD, bone biomarkers, mechanical failure properties, and lipid levels similar to those of OVX controls.
Conclusions: EXE and 17-H-EXE significantly prevent bone loss, enhance bone mechanical strength, and lower serum cholesterol and low-density lipoprotein levels in OVX rats. These protective effects on end-organ function are not seen with the nonsteroidal inhibitor LET.
A Global Expression-based Analysis of the Consequences of the t(4;14) Translocation in Myeloma
Authors: Dring Ann M. , Davies Faith E. , Fenton James A. L. , Roddam Philippa L. , Scott Kathryn , Gonzalez David , Rollinson Sara , Rawstron Andrew C. , Rees-Unwin Karen S. , Li Cheng , Munshi Nikhil C. , Anderson Kenneth C. , Morgan Gareth J. 
Published: September 2005

AbstractPurpose: Our purpose in this report was to define genes and pathways dysregulated as a consequence of the t(4;14) in myeloma, and to gain insight into the downstream functional effects that may explain the different prognosis of this subgroup.Experimental Design: Fibroblast growth factor receptor 3 (FGFR3) overexpression, the presence of immunoglobulin heavy chain-multiple myeloma SET domain (IgH-MMSET) fusion products and the identification of t(4;14) breakpoints were determined in a series of myeloma cases. Differentially expressed genes were identified between cases with (n = 5) and without (n = 24) a t(4;14) by using global gene expression analysis.Results: Cases with a t(4;14) have a distinct expression pattern compared with other cases of myeloma. A total of 127 genes were identified as being differentially expressed including MMSET and cyclin D2, which have been previously reported as being associated with this translocation. Other important functional classes of genes include cell signaling, apoptosis and related genes, oncogenes, chromatin structure, and DNA repair genes. Interestingly, 25% of myeloma cases lacking evidence of this translocation had up-regulation of the MMSET transcript to the same level as cases with a translocation.Conclusions: t(4;14) cases form a distinct subgroup of myeloma cases with a unique gene signature that may account for their poor prognosis. A number of non-t(4;14) cases also express MMSET consistent with this gene playing a role in myeloma pathogenesis.
Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses
Authors: Monji Mikio , Nakatsura Tetsuya , Senju Satoru , Yoshitake Yoshihiro , Sawatsubashi Motohiro , Shinohara Masanori , Kageshita Toshiro , Ono Tomomichi , Inokuchi Akira , Nishimura Yasuharu 
Published: September 2005

Abstract
Purpose: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/testis antigens that elicit both humoral and cellular immune responses in cancer patients.
Experimental Design and Results: We identified a novel gene designated KM-HN-1 the expression of which is testis-specific among normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402–positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24.
Conclusions: We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.
Loss of Parafibromin Immunoreactivity Is a Distinguishing Feature of Parathyroid Carcinoma
Authors: Tan Min-Han , Morrison Carl , Wang Pengfei , Yang Ximing , Haven Carola J. , Zhang Chun , Zhao Ping , Tretiakova Maria S. , Korpi-Hyovalti Eeva , Burgess John R. , Soo Khee Chee , Cheah Wei-Keat , Cao Brian , Resau James , Morreau Hans , Teh Bin Tean 
Published: September 2005

Abstract
Purpose: A reliable method for diagnosing parathyroid carcinoma has remained elusive over the years, resulting in its under-recognition and suboptimal therapy. Obtaining an accurate diagnosis has become an even more pressing matter with recent evidence that germline HRPT2 gene mutations are found in patients with apparently sporadic parathyroid carcinoma. There is a high prevalence of HRPT2 gene mutations and biallelic inactivation in parathyroid carcinoma. We hypothesize that loss of parafibromin, the protein product of the HRPT2 gene, would distinguish carcinoma from benign tissue.
Experimental Design: We generated a novel antiparafibromin monoclonal antibody and performed immunostaining on 52 definite carcinoma specimens, 6 equivocal carcinoma specimens, 88 benign specimens, and 9 hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from patients with primary hyperparathyroidism from nine worldwide centers and one national database.
Results: We report that the loss of parafibromin nuclear immunoreactivity has 96% sensitivity [95% confidence interval (CI), 85–99%] and 99% specificity (95% CI, 92–100%) in diagnosing definite carcinoma. Inter-observer agreement for evaluation of parafibromin loss was excellent, with unweighted kappa of 0.89 (95% CI, 0.79–0.98). Two equivocal carcinomas misclassified as adenomas were highlighted by parafibromin immunostaining. One of these tumors has since recurred, satisfying criteria for a definite carcinoma. Similarly, eight of nine HPT-JT syndrome-related adenomas showed absent nuclear immunoreactivity.
Conclusions: Parafibromin is a promising molecular marker for diagnosing parathyroid carcinoma. The similar loss of parafibromin immunoreactivity in HPT-JT syndrome-related adenomas suggests that this is a pivotal step in parathyroid tumorigenesis.
The Spontaneous CD8+ T-Cell Response to HLA-A2-Restricted NY-ESO-1b Peptide in Hepatocellular Carcinoma Patients
Authors: Shang Xiao-Ying , Chen Hong-Song , Zhang Hua-Gang , Pang Xue-Wen , Qiao Huan , Peng Ji-Run , Qin Li-Ling , Fei Ran , Mei Ming-Hui , Leng Xi-Sheng , Gnjatic Sacha , Ritter Gerd , Simpson Andrew J. G. , Old Lloyd J. , Chen Wei-Feng 
Published: September 2005

AbstractPurpose: Hepatocellular carcinoma (HCC) can express various cancer-testis antigens including NY-ESO-1, members of the SSX family, members of the MAGE family, SCP-1, and CTP11. Immunotherapy directed against these antigens is a potential alternative treatment for HCC. To date, it remains unclear whether HCC patients have spontaneous immune responses to these tumor antigens. The objectives of this study were to measure immune responses to NY-ESO-1, a promising cancer vaccine candidate, in HCC patients using the HLA-A2–restricted NY-ESO-1b peptide (p157-165) to measure cellular responses and whole protein to measure antibody responses.Experimental Design: In HLA-A2+ patients with NY-ESO-1+ HCC, we analyzed T-cell antigen-dependent interferon (IFN)-γ and/or Granzyme B release by enzyme-linked immunospot (ELISPOT) assay and IFN-γ–producing intracellular cytokine flow cytometry (CytoSpot). As an assay independent of T-cell function, we performed tetramer staining. Antibodies to whole NY-ESO-1 were assayed by enzyme-linked immunosorbent assay.Results: The frequency of specific CD8+ T-cell responses to NY-ESO-1b in 28 NY-ESO-1 mRNA+HLA-A2+ HCC patients was 35.7% (10 of 28). The average magnitude of effector CD8+ T cells was 0.3% (89 ± 59 per 2.5 × 104 CD8+ cells) and 1.2% as measured by IFN-γ release ELISPOT and CytoSpot assays, respectively. These in vitro induced NY-ESO-1b–specific CD8+ T cells can also recognize HepG2 cells transfected with pcDNA3.1-NY-ESO-1 in both IFN-γ and Granzyme B ELISPOT assays. Frequencies of NY-ESO-1b–specific T cells in several patients were confirmed by tetramer staining. Nonfunctional tetramer+CD8+ T cells were also present. The CD8+ T-cell response was apparently increased in patients with late-stage HCC. A discordance between antibody and CD8+ T-cell responses in HCC patients was observed.Conclusions: The elevated frequency of specific CD8+ T-cell responses to NY-ESO-1b in NY-ESO-1 mRNA+HLA-A2+ HCC patients suggests that NY-ESO-1 is appropriate for use in the immunotherapy of HCC patients.
Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors
Authors: Parrella Paola , Poeta Maria Luana , Gallo Antonietta Pia , Prencipe Maria , Scintu Marina , Apicella Adolfo , Rossiello Raffaele , Liguoro Giuseppina , Seripa Davide , Gravina Carolina , Rabitti Carla , Rinaldi Monica , Nicol Theresa , Tommasi Stefania , Paradiso Angelo , Schittulli Francesco , Altomare Vittorio , Fazio Vito Michele 
Published: September 2005

Abstract
Purpose: In an effort to additionally determine the global patterns of CpG island hypermethylation in sporadic breast cancer, we searched for aberrant promoter methylation at 10 gene loci in 54 primary breast cancer and 10 breast benign lesions.
Experimental Design: Genomic DNA sodium bisulfate converted from benign and malignant tissues was used as template in methyl-specific PCR for BRCA1, p16, ESR1, GSTP1, TRβ1, RARβ2, HIC1, APC, CCND2, and CDH1 genes.
Results: The majority of the breast cancer (85%) showed aberrant methylation in at least 1 of the loci tested with half of them displaying 3 or more methylated genes. The highest frequency of aberrant promoter methylation was found for HIC1 (48%) followed by ESR1 (46%), and CDH1 (39%). Similar methylation frequencies were detected for breast benign lesions with the exception of the CDH1 gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRβ1, GSTP1, and CCND2 loci (P &lt; 0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARβ2 locus (P &lt; 0.03).
Conclusions: Our results suggest a nonrandom distribution for promoter hypermethylation in sporadic breast cancer, with tumor subsets characterized by aberrant methylation of specific cancer-related genes. These breast cancer subgroups may represent separate biological entities with potential differences in sensitivity to therapy, occurrence of metastasis, and overall prognosis.
Overexpression of the Nuclear Receptor Coactivator
AIB1
(
SRC-3
) during Progression of Pancreatic Adenocarcinoma
Authors: Henke Ralf Thorsten , Haddad Bassem R. , Kim Sung Eun , Rone Janice Dalby , Mani Aparna , Jessup John Milburn , Wellstein Anton , Maitra Anirban , Riegel Anna Tate 
Published: September 2005

Abstract
Purpose: The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) was found to be amplified and overexpressed in breast and some other epithelial tumors. We have reported that expression of AIB1 is rate limiting for growth factor, as well as hormone signaling. Here, we assess the involvement of AIB1 in the development of pancreatic adenocarcinoma.
Experimental Design: We investigated expression levels of AIB1 protein and mRNA in pancreatic cancer cell lines and in a series of archival pancreatic adenocarcinoma (n = 78), pancreatic intraepithelial neoplasia (n = 93), pancreatitis (n = 28), and normal pancreas tissues (n = 52). We also determined AIB1 gene copy numbers by fluorescence in situ hybridization in a subset of cases.
Results: In normal pancreas ducts, we rarely found detectable levels of AIB1 mRNA or protein (&lt;6% of the samples). In pancreatitis and low-grade intraepithelial neoplasia, we found an increased frequency of AIB1 expression (&gt;14 and &gt;23%, respectively) relative to normal tissues (P &lt; 0.01). Adenocarcinoma, as well as high-grade intraepithelial neoplasia, showed increased levels as well as the highest frequency of AIB1 expression with &gt;65% of samples positive for mRNA and protein (P &lt; 0.0001 relative to the other groups). An increased copy number of the AIB1 gene, observed in 37% of cancers, may account for a portion of the increase in expression.
Conclusions: AIB1 overexpression is frequent in pancreatic adenocarcinoma and its precursor lesions. On the basis of its rate-limiting role for the modulation of growth factor signals, we propose a major role of AIB1 in the multistage progression of pancreatic cancer.