bluuebunny/crossref_metadata_2025_split huggingface dataset:
Y Chromosome Haplotypes and Prostate Cancer in Sweden
Authors: Lindström Sara , Adami Hans-Olov , Adolfsson Jan , Wiklund Fredrik 
Published: October 2008

Abstract
Purpose: Certain Y-chromosomal lineages have been suggested to predispose individuals to prostate cancer in the Japanese population; in other ethnic groups, however, the importance of the Y chromosome is poorly understood.
Experimental Design: To assess the possible Y-chromosomal contribution to prostate cancer risk and prognosis, we analyzed five binary Y-chromosomal markers in 1,447 prostate cancer cases and 983 population controls from the Swedish population. Together, these five markers capture the vast majority of chromosome Y haplogroup diversity in the Swedish population. Individual lineages were tested for association with both prostate cancer risk and cancer-specific death. We replicated observed associations in an independent Swedish prostate cancer case-control study comprising 1,452 cases and 779 controls.
Results: One rare lineage (I1c) was associated with an increased risk of developing prostate cancer [odds ratio (OR), 2.9; 95% confidence interval (CI), 1.4-5.8; P = 0.001]. However, confirmatory analysis of this lineage in the independent case-control study revealed no association with prostate cancer risk (OR, 0.65; 95% CI, 0.4-1.2, P = 0.17). We observed no association between chromosome Y variation and prostate cancer–specific death.
Conclusions: This study provides strong evidence against an important role of the Y chromosome in the initiation or outcome of prostate cancer in the Swedish population.
Novel Strategies for Granulocyte Colony-Stimulating Factor Treatment of Severe Prolonged Neutropenia Suggested by Mathematical Modeling
Authors: Shochat Eliezer , Rom-Kedar Vered 
Published: October 2008

Abstract
Purpose: To improve the effectiveness of granulocyte colony-stimulating factor (G-CSF) treatment in high-risk neutropenic patients.
Experimental Design: We study G-CSF effects on chemotherapy-induced neutropenia by expanding a simple mathematical model of neutrophil dynamics in the blood. The final model is fitted and validated using published clinical data of neutrophil response to chemotherapy and standard s.c. G-CSF protocol (SG; filgrastim 5 μg/kg/d), single pegylated (pegG; pegfilgrastim 100 μg/kg), and continuous infusion (CG; filgrastim 10 μg/kg/d). The interpatient variability is studied by Monte-Carlo simulation of pegG compared with SG and placebo.
Results: The effect G-CSF support on neutropenia depends on the neutrophil count at the nadir. Three distinct neutropenia grades are identified: G1 (300 × 103−500 × 103 cells/mL), G2 (50 × 103−300 × 103 cells/mL), and G3 (≤50 × 103 cells/mL). For many G2 patients, the G-CSF levels required for recovery are not attainable by the standard regimen, whereas the sustained pegG and CG seem to be significantly more effective. For G3 patients, G-CSF support alone is not sufficient and additional clinical approaches should be considered. The results presented here are robust and are only slightly affected by population variability.
Conclusions: The model captures the G-CSF-neutrophil dynamics of severe chemotherapy-induced neutropenia. Our results clarify and complement the current American Society of Clinical Oncology recommendations for G-CSF administration in neutropenia: High sustained G-CSF levels are needed to treat severe neutropenia and may be achieved by either CG or pegG. The potential effect of sustained G-CSF on severe neutropenia should be studied within a framework of a prospective randomized clinical trial.
The Desmoplastic Reaction Surrounding Hepatic Colorectal Adenocarcinoma Metastases Aids Tumor Growth and Survival via αv Integrin Ligation
Authors: Conti John A. , Kendall Timothy J. , Bateman Adrian , Armstrong Thomas A. , Papa-Adams Andrew , Xu Qian , Packham Graham , Primrose John N. , Benyon R. Christopher , Iredale John P. 
Published: October 2008

Abstract
Purpose: The treatment of metastatic colorectal carcinoma represents a major clinical challenge. We investigated the hypothesis that the desmoplastic reaction within the liver elicited by metastatic adenocarcinoma, characterized by collagen I deposition and altered collagen IV distribution, promotes the growth and survival of hepatic colorectal carcinoma metastases.
Experimental Design: Partial hepatectomy specimens for metastatic colorectal adenocarcinoma were examined immunohistochemically for differential integrin expression. Human colorectal adenocarcinoma cell lines HT-29, KM12SM, and KM12c were grown on wild-type collagen I or IV, or cleavage-resistant r/r collagen I, and assessed for their growth, survival, and resistance to 5-fluorouracil. The effect of αvβ3 and αvβ5 integrin blockade by neutralizing antibodies was examined.
Results: Collagen I, in contrast to collagen IV, significantly enhanced the growth, survival, and chemoresistance of colorectal carcinoma cells. Blockade of the αvβ3 and αvβ5 integrins significantly reduced colorectal carcinoma cell proliferation on collagen, especially in the cell line with the most metastatic potential. These in vitro findings correlated with the pattern of integrin expression identified within resected hepatic colorectal carcinoma metastases. Using matrix metalloproteinase-resistant r/r collagen I as a dominant negative ligand for αv integrins, we showed a key role for this integrin-ligand interaction in mediating the survival and proliferation of colorectal carcinoma cells.
Conclusions: Desmoplasia has an important role in the development of hepatic colorectal carcinoma metastasis. The interaction between integrin and collagen I is identified as a potential therapeutic target.
Multiplex Reverse Transcription-PCR Screening for EML4-ALK Fusion Transcripts
Authors: Takeuchi Kengo , Choi Young Lim , Soda Manabu , Inamura Kentaro , Togashi Yuki , Hatano Satoko , Enomoto Munehiro , Takada Shuji , Yamashita Yoshihiro , Satoh Yukitoshi , Okumura Sakae , Nakagawa Ken , Ishikawa Yuichi , Mano Hiroyuki 
Published: October 2008

Abstract
Purpose: EML4-ALK is a fusion-type protein tyrosine kinase that is generated by inv(2)(p21p23) in the genome of non–small cell lung cancer (NSCLC). To allow sensitive detection of EML4-ALK fusion transcripts, we have now developed a multiplex reverse transcription-PCR (RT-PCR) system that captures all in-frame fusions between the two genes.
Experimental Design: Primers were designed to detect all possible in-frame fusions of EML4 to exon 20 of ALK, and a single-tube multiplex RT-PCR assay was done with total RNA from 656 solid tumors of the lung (n = 364) and 10 other organs.
Results: From consecutive lung adenocarcinoma cases (n = 253), we identified 11 specimens (4.35%) positive for fusion transcripts, 9 of which were positive for the previously identified variants 1, 2, and 3. The remaining two specimens harbored novel transcript isoforms in which exon 14 (variant 4) or exon 2 (variant 5) of EML4 was connected to exon 20 of ALK. No fusion transcripts were detected for other types of lung cancer (n = 111) or for tumors from 10 other organs (n = 292). Genomic rearrangements responsible for the fusion events in NSCLC cells were confirmed by genomic PCR analysis and fluorescence in situ hybridization. The novel isoforms of EML4-ALK manifested marked oncogenic activity, and they yielded a pattern of cytoplasmic staining with fine granular foci in immunohistochemical analysis of NSCLC specimens.
Conclusions: These data reinforce the importance of accurate diagnosis of EML4-ALK–positive tumors for the optimization of treatment strategies.
A New Therapeutic Strategy against Hormone-Dependent Breast Cancer: The Preclinical Development of a Dual Aromatase and Sulfatase Inhibitor
Authors: Foster Paul A. , Chander Surinder K. , Newman Simon P. , Woo L.W. Lawrence , Sutcliffe Oliver B. , Bubert Christian , Zhou Dujin , Chen Shiuan , Potter Barry V.L. , Reed Michael J. , Purohit Atul 
Published: October 2008

AbstractPurpose: The production of E2 is paramount for the growth of estrogen receptor–positive breast cancer. Various strategies have been used, including the use of enzyme inhibitors against either aromatase (AROM) or steroid sulfatase (STS), in an attempt to ablate E2 levels. Both these enzymes play a critical role in the formation of estrogenic steroids and their inhibitors are now showing success in the clinic.Experimental Design: We show here, in a xenograft nude mouse model, that the inhibition of both enzymes using STX681, a dual AROM and STS inhibitor (DASI), is a potential new therapeutic strategy against HDBC. MCF-7 cells stably expressing either AROM cDNA (MCF-7AROM) or STS cDNA (MCF-7STS) were generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of either androstenedione (A4) or E2 sulfate and bearing either MCF-7AROM or MCF-7STS tumors were orally treated with STX64, letrozole, or STX681. Treatment was administered for 28 days. Mice were weighed and tumor measurements were taken weekly.Results: STX64, a potent STS inhibitor, completely blocked MCF-7STS tumor growth but failed to attenuate MCF-7AROM tumor growth. In contrast, letrozole inhibited MCF-7AROM tumors but had no effect on MCF-7STS tumors. STX681 completely inhibited the growth of both tumors. AROM and STS activity was also completely inhibited by STX681, which was accompanied by a significant reduction in plasma E2 levels.Conclusions: This study indicates that targeting both the AROM and the STS enzyme with a DASI inhibits HDBC growth and is therefore a potentially novel treatment for this malignancy.
Identification of a Novel Tumor-Associated Antigen, Cadherin 3/P-Cadherin, as a Possible Target for Immunotherapy of Pancreatic, Gastric, and Colorectal Cancers
Authors: Imai Katsunori , Hirata Shinya , Irie Atsushi , Senju Satoru , Ikuta Yoshiaki , Yokomine Kazunori , Harao Michiko , Inoue Mitsuhiro , Tsunoda Takuya , Nakatsuru Shuichi , Nakagawa Hidewaki , Nakamura Yusuke , Baba Hideo , Nishimura Yasuharu 
Published: October 2008

AbstractPurpose: To establish cancer immunotherapy, it is important to identify the tumor-associated antigens (TAA) that are strongly expressed in the tumor cells but not in the normal cells. In this study, to establish an effective anticancer immunotherapy, we tried to identify the useful TAA of pancreatic cancer.Experimental Design: Based on a previous genome-wide cDNA microarray analysis of pancreatic cancer, we focused on cadherin 3 (CDH3)/P-cadherin as a novel candidate TAA for anticancer immunotherapy. To identify the HLA-A2 (A*0201)–restricted CTL epitopes of CDH3, we used HLA-A2.1 (HHD) transgenic mice (Tgm). Furthermore, we examined the cytotoxicity against the tumor cells in vitro and in vivo of CTLs specific to CDH3 induced from HLA-A2–positive healthy donors and cancer patients.Results: CDH3 was overexpressed in the majority of pancreatic cancer and various other malignancies, including gastric and colorectal cancers, but not in their noncancerous counterparts or in many normal adult tissues. In the experiment using HLA-A2.1 Tgm, we found that the CDH3-4655-663 (FILPVLGAV) and CDH3-7757-765 (FIIENLKAA) peptides could induce HLA-A2–restricted CTLs in Tgm. In addition, peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A2–positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both CDH3 and HLA-A2. Furthermore, the adoptive transfer of the CDH3-specific CTLs could inhibit the tumor growth of human cancer cells engrafted into nonobese diabetic/severe combined immunodeficiency mice.Conclusions: These results suggest that CDH3 is a novel TAA useful for immunotherapy against a broad spectrum of cancers, including pancreatic cancer.
αv Integrins Lead the Way for Colorectal Metastases
Authors: McCarty Joseph H. 
Published: October 2008

Abstract
In this issue of Clinical Cancer Research, Conti et al. identify a crucial cell adhesion and signaling axis that promotes the proliferation, survival, and drug-resistant properties of metastatic colorectal cancer cells in the liver. The components of this pathway may be effective targets for therapeutically treating established metastatic tumors in patients with colorectal adenocarcinomas.
Cognitive functioning in children with multiple sclerosis
Authors: Montiel-Nava C , Peña JA , González-Pernía S , Mora-La Cruz E 
Published: October 2008

Objective To examine the cognitive functioning of children with multiple sclerosis (MS). Methods Six children with a diagnosis of clinically definite MS were evaluated using a neuropsychological test battery. Results The majority of the children showed deficits in at least two of the administered subtests, with IQ scores within the deficient classification. Conclusions Verbal and non-verbal skills were equally impaired, and patients who were older at the moment of the onset of the disease had a better cognitive performance. Cognitive deficits should be regarded as a common occurrence in the course of MS in children.
A peptomimetic inhibitor of BCL6 with potent antilymphoma effects in vitro and in vivo
Authors: Cerchietti Leandro C. , Yang Shao Ning , Shaknovich Rita , Hatzi Katerina , Polo Jose M. , Chadburn Amy , Dowdy Steven F. , Melnick Ari 
Published: October 2008

Abstract
The BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCLs). BCL6 lymphomagenic activity is dependent on its ability to recruit corepressor proteins to a unique binding site on its N-terminal BTB domain. A recombinant peptide fragment of the SMRT (silencing mediator for retinoid and thyroid hormone receptor) corepressor that blocks this site can inhibit BCL6 biologic functions. Shortening and conversion of this peptide to D-amino acid and retro configuration as well as the addition of a fusogenic motif yielded a far more potent and stable BCL6 inhibitor that still retained the specificity of the original SMRT fragment. Like the L-peptide, retroinverso BCL6 peptide inhibitor (RI-BPI) selectively killed BCR rather than OxPhos-type DLBCL cells. The RI-BPI could recapitulate the failure to form germinal centers seen in BCL6 null mice yet was nontoxic and nonimmunogenic even when administered for up to 52 weeks. RI-BPI showed superior duration of tissue penetration and could accordingly powerfully suppress the growth of human DLBCLs xenografts in a dose-dependent manner. Finally, RI-BPI could kill primary human DLBCL cells but had no effect on normal lymphoid tissue or other tumors.
Structural assembly of two-domain proteins by rigid-body docking
Authors: Cheng Tammy MK , Blundell Tom L , Fernandez-Recio Juan 
Published: October 2008

Abstract

Background
Modelling proteins with multiple domains is one of the central challenges in Structural Biology. Although homology modelling has successfully been applied for prediction of protein structures, very often domain-domain interactions cannot be inferred from the structures of homologues and their prediction requires ab initio methods. Here we present a new structural prediction approach for modelling two-domain proteins based on rigid-body domain-domain docking.

Results
Here we focus on interacting domain pairs that are part of the same peptide chain and thus have an inter-domain peptide region (so called linker). We have developed a method called pyDockTET (tet hered-docking), which uses rigid-body docking to generate domain-domain poses that are further scored by binding energy and a pseudo-energy term based on restraints derived from linker end-to-end distances. The method has been benchmarked on a set of 77 non-redundant pairs of domains with available X-ray structure. We have evaluated the docking method ZDOCK, which is able to generate acceptable domain-domain orientations in 51 out of the 77 cases. Among them, our method pyDockTET finds the correct assembly within the top 10 solutions in over 60% of the cases. As a further test, on a subset of 20 pairs where domains were built by homology modelling, ZDOCK generates acceptable orientations in 13 out of the 20 cases, among which the correct assembly is ranked lower than 10 in around 70% of the cases by our pyDockTET method.

Conclusion
Our results show that rigid-body docking approach plus energy scoring and linker-based restraints are useful for modelling domain-domain interactions. These positive results will encourage development of new methods for structural prediction of macromolecules with multiple (more than two) domains.
A comparison of cecal colonization of Salmonella enterica serotype Typhimurium in white leghorn chicks and Salmonella-resistant mice
Authors: Sivula Christine P , Bogomolnaya Lydia M , Andrews-Polymenis Helene L 
Published: October 2008

AbstractBackgroundSalmonellosis is one of the most important bacterial food borne illnesses worldwide. A major source of infection for humans is consumption of chicken or egg products that have been contaminated withSalmonella entericaserotype Typhimurium, however our knowledge regarding colonization and persistence factors in the chicken is small.ResultsWe compared intestinal and systemic colonization of 1-week-old White Leghorn chicks andSalmonella-resistant CBA/J mice during infection withSalmonella entericaserotype Typhimurium ATCC14028, one of the most commonly studied isolates. We also studied the distribution of wild type serotype Typhimurium ATCC14028 and an isogenicinvAmutant during competitive infection in the cecum of 1-week-old White Leghorn chicks and 8-week-old CBA/J mice. We found that although the systemic levels of serotype Typhimurium in both infected animal models are low, infected mice have significant splenomegaly beginning at 15 days post infection. In the intestinal tract itself, the cecal contents are the major site for recovery of serotype Typhimurium in the cecum of 1-week-old chicks andSalmonella-resistant mice. Additionally we show that only a small minority ofSalmonellaeare intracellular in the cecal epithelium of both infected animal models, and while SPI-1 is important for successful infection in the murine model, it is important for association with the cecal epithelium of 1-week-old chicks. Finally, we show that in chicks infected with serotype Typhimurium at 1 week of age, the level of fecal shedding of this organism does not reflect the level of cecal colonization as it does in murine models.ConclusionIn our study, we highlight important differences in systemic and intestinal colonization levels between chick and murine serotype Typhimurium infections, and provide evidence that suggests that the role of SPI-1 may not be the same during colonization of both animal models.
Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?
Authors: Ben-Smith Anne , Gorak-Stolinska Patricia , Floyd Sian , Weir Rosemary E , Lalor Maeve K , Mvula Hazzie , Crampin Amelia C , Wallace Diana , Beverley Peter CL , Fine Paul EM , Dockrell Hazel M 
Published: October 2008

AbstractBackgroundDifferences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years.MethodsVenous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents.ResultsHIV-negative Malawian adolescents were shown to have a lower percentage of naïve T cells (CD45RO-CD62LhiCD11alo), a higher proportion of memory T cells and a higher percentage of CD28-memory (CD28-CD45RO+) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+) T cells and a higher percentage of stable memory (CD45RA+CCR7-) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naïve T cells and an increased percentage of CD28-memory T cells in the periphery. No differences in the proportions of naïve and memory T cell populations were observed in cord blood samples from the two sites.ConclusionIt is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.
Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper
Authors: Jensen Mette Munk , Jørgensen Jesper Tranekjær , Binderup Tina , Kjær Andreas 
Published: October 2008

Abstract

Background
In animal studies tumor size is used to assess responses to anticancer therapy. Current standard for volumetric measurement of xenografted tumors is by external caliper, a method often affected by error. The aim of the present study was to evaluate if microCT gives more accurate and reproducible measures of tumor size in mice compared with caliper measurements. Furthermore, we evaluated the accuracy of tumor volume determined from 18F-fluorodeoxyglucose (18F-FDG) PET.

Methods
Subcutaneously implanted human breast adenocarcinoma cells in NMRI nude mice served as tumor model. Tumor volume (n = 20) was determined in vivo by external caliper, microCT and 18F-FDG-PET and subsequently reference volume was determined ex vivo. Intra-observer reproducibility of the microCT and caliper methods were determined by acquiring 10 repeated volume measurements. Volumes of a group of tumors (n = 10) were determined independently by two observers to assess inter-observer variation.

Results
Tumor volume measured by microCT, PET and caliper all correlated with reference volume. No significant bias of microCT measurements compared with the reference was found, whereas both PET and caliper had systematic bias compared to reference volume. Coefficients of variation for intra-observer variation were 7% and 14% for microCT and caliper measurements, respectively. Regression coefficients between observers were 0.97 for microCT and 0.91 for caliper measurements.

Conclusion
MicroCT was more accurate than both caliper and 18F-FDG-PET for in vivo volumetric measurements of subcutaneous tumors in mice.18F-FDG-PET was considered unsuitable for determination of tumor size. External caliper were inaccurate and encumbered with a significant and size dependent bias. MicroCT was also the most reproducible of the methods.