bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal screening for sickle cell disease in France: evaluation of the selective process: Table 1
Authors: Thuret Isabelle , Sarles Jacques , Merono Françoise , Suzineau Eliane , Collomb Jacques , Lena-Russo Danielle , Levy Nicolas , Bardakdjian Josiane , Badens Catherine 
Published: May 2010

AimsThe French national programme for neonatal screening of sickle cell disease is applied to newborns ‘at risk’, defined as those born to parents originating from sub-Saharan Africa, the Mediterranean area, the Arabic peninsula, the French overseas islands and the Indian subcontinent. The selection is performed by the nurse in charge of blood sampling by interviewing the mother about the family's geographical origins. The mean rate of testing in France is 25%, ranging from 2% to 50% depending on the region. This study aimed to evaluate the effectiveness of selection during this screening programme.MethodsFalse-negative cases were identified using two different approaches: first, a regional prospective study aimed at screening all newborns, selected and non-selected, in a restricted area, representing 3% of national births; second, a retrospective national survey to identify false-negative cases.ResultsThe regional study indicated that selective screening leads to a carrier frequency that is twice as high in the selected population as compared with the non-selected population (1.23% versus 0.62%). The local and national surveys revealed that, during a 6-year period, 28 affected children failed to be selected, leading to a false-negative rate of 2.1%. In contrast to what was expected, most of the cases were due to the failing of the data collection process and not to the misdiagnosis of the risk.ConclusionsThese results show that selective neonatal screening for sickle cell disease is feasible if very careful attention is paid to the selective step.
Comparison of histopathology and RT-qPCR amplification of guanylyl cyclase C for detection of colon cancer metastases in lymph nodes
Authors: Haince Jean-François , Houde Michel , Beaudry Guillaume , L'Espérance Sylvain , Garon Geneviève , Desaulniers Marie , Hafer Laurie J , Heald James I , Lyle Stephen , Grossman Steven R , Têtu Bernard , Sargent Daniel J , Fradet Yves 
Published: May 2010

AimsIn colorectal cancer (CRC), the presence of lymph node (LN) metastases is an important prognostic factor. Approximately 20% of patients diagnosed as having node-negative (pN0) CRC will relapse. Pathological nodal stage misclassification due to sampling error resulting from the small volume of tissue tested has been proposed to explain this recurrence rate in pN0 patients. The authors compared the assessment of node positivity by histopathology (HP) with a molecular method which can accommodate larger tissue volumes.MethodsDetection rate of guanylyl cyclase C (GCC) mRNA was determined in 1495 LNs from 99 CRC patients. Using a subset of 647 LNs, multiple levels of HP analysis were compared with GCC mRNA molecular detection. Finally, clinicopathological factors were correlated with the molecular detection of GCC and clinical outcome in 123 patients with pN0 colon cancer.ResultsGCC mRNA was detected in 8.0% of the 560 nodes initially identified as HP-negative, whereas two repeat HP examinations detected 3.0% of these cases. In HP-positive LNs, the GCC mRNA detection rate was 90% (78/87) when half-LN were tested. Testing the entire LN remaining after HP by GCC increased the detection rate of HP-positive LNs to 95% (p=0.027). In comparison, 75% (65/87) and 92% (80/87) of the LN positive by clinical HP remained positive when one or two subsequent sections were examined by HP. Finally, patients with pN0 disease who were GCC-positive exhibited an earlier time of recurrence (hazard ratio, 3.54; 95% CI 1.40 to 8.98; p=0.0077).ConclusionsMolecular detection of tumour cells in LNs may have prognostic value in identifying patients diagnosed as having pN0 colon cancer who will relapse following surgery.
Percutaneous medical liver core biopsies: correlation between tissue length and the number of portal tracts
Authors: Chan James , Alwahab Yasir , Tilley Charles , Carr Norman 
Published: May 2010

ObjectiveLiver biopsy is an important tool for the diagnosis and assessment of liver disease. The authors aimed to establish the relationship between biopsy length and the number of total portal tracts.MethodsThe authors reviewed 163 16G percutaneous medical liver biopsies taken at a tertiary referral centre over a 14-month period. Haematoxylin and eosin sections were analysed using imaging software and portal tracts were counted.ResultsLiver biopsy length correlates with total portal tracts. The median biopsy length was 13.3 mm with a median of six portal tracts. Ninety-five per cent of biopsies measuring at least 15 mm contained six portal tracts or more with a significant difference between total portal tracts when compared with biopsies <15 mm (p<0.0001).ConclusionTo facilitate adequate histological assessment by examining at least six portal tracts, the authors suggest that 16G biopsies should be at least 15 mm long.
Taking stock: defining populations of American shad (Alosa sapidissima) in Canada using neutral genetic markers
Authors: Hasselman Daniel J. , Bradford Rod G. , Bentzen Paul 
Published: May 2010

Knowledge of the scale of population structure is a prerequisite for designating conservation units. American shad ( Alosa sapidissima ) are of increasing conservation concern, but the scale of population structure within the Canadian portion of the species range is unknown. Using 13 microsatellite loci, we examined the partitioning of genetic variation within four and among 12 Canadian drainages. We detected significant (p < 0.05) and temporally stable genetic differentiation among all drainages, supporting the hypothesis that rivers support genetically distinct populations. However, Bayesian methods identified seven clusters and provided evidence for shad metapopulation structure. We observed a significant (p < 0.01) pattern of isolation by distance (IBD) among all drainages. A strong linear IBD (r = 0.98) was observed among rivers that were outside the Bay of Fundy (BoF). A hypothesized counterclockwise migration route explained a greater proportion of genetic variation (r = 0.87) among BoF rivers than direct route based distances (r = 0.14). Although IBD patterns did not differ regionally (analysis of covariance; p > 0.05), the degree of differentiation among BoF rivers was greater than that among non-BoF rivers, regardless of the geographic scale of comparison. Our results suggest that fisheries managers need to be concerned with the loss of shad genetic diversity on both river and regional scales.
LOWER BOUNDS FOR THE NORMALIZED HEIGHT AND NON-DENSE SUBSETS OF SUBVARIETIES OF ABELIAN VARIETIES
Authors: VIADA EVELINA 
Published: May 2010

This work is the third part of a series of papers. In the first two, we considered curves and varieties in a power of an elliptic curve. Here, we deal with subvarieties of an abelian variety in general. Let V be a proper irreducible subvariety of dimension d in an abelian variety A, both defined over the algebraic numbers. We say that V is weak-transverse if V is not contained in any proper algebraic subgroup of A, and transverse if it is not contained in any translate of such a subgroup. Assume a conjectural lower bound for the normalized height of V. Then, for V transverse, we prove that the algebraic points of bounded height of V which lie in the union of all algebraic subgroups of A of codimension at least d + 1 translated by the points close to a subgroup Γ of finite rank, are non-Zariski-dense in V. If Γ has rank zero, it is sufficient to assume that V is weak-transverse. The notion of closeness is defined using a height function.
Immune Infiltration of Spontaneous Mouse Astrocytomas Is Dominated by Immunosuppressive Cells from Early Stages of Tumor Development
Authors: Tran Thang Nhu Nam , Derouazi Madiha , Philippin Géraldine , Arcidiaco Séverine , Di Berardino-Besson Wilma , Masson Frédérick , Hoepner Sabine , Riccadonna Cristina , Burkhardt Karim , Guha Abhijit , Dietrich Pierre-Yves , Walker Paul R. 
Published: May 2010

Abstract
Immune infiltration of advanced human gliomas has been shown, but it is doubtful whether these immune cells affect tumor progression. It could be hypothesized that this infiltrate reflects recently recruited immune cells that are immediately overwhelmed by a high tumor burden. Alternatively, if there is earlier immune detection and infiltration of the tumor, the question arises as to when antitumor competency is lost. To address these issues, we analyzed a transgenic mouse model of spontaneous astrocytoma (GFAP-V12HA-ras mice), which allows the study of immune interactions with developing glioma, even at early asymptomatic stages. T cells, including a significant proportion of Tregs, are already present in the brain before symptoms develop, followed later by macrophages, natural killer cells, and dendritic cells. The effector potential of CD8 T-cells is defective, with the absence of granzyme B expression and low expression of IFN-γ, tumor necrosis factor, and interleukin 2. Overall, our results show an early defective endogenous immune response to gliomas, and local accumulation of immunosuppressive cells at the tumor site. Thus, the antiglioma response is not simply overwhelmed at advanced stages of tumor growth, but is counterbalanced by an inhibitory microenvironment from the outset. Nevertheless, we determined that effector molecule expression (granzyme B, IFN-γ) by brain-infiltrating CD8 T-cells could be enhanced, despite this unfavorable milieu, by strong immune stimuli. This potential to modulate the strong imbalance in local antiglioma immunity is encouraging for the development and optimization of future glioma immunotherapies. Cancer Res; 70(12); 4829–39. ©2010 AACR.
Breast Cancer Dormancy Can Be Maintained by Small Numbers of Micrometastases
Authors: Willis Lisa , Alarcón Tomas , Elia George , Jones J. Louise , Wright Nick A. , Tomlinson Ian P.M. , Graham Trevor A. , Page Karen M. 
Published: May 2010

AbstractLate relapse of breast cancer can occur more than 25 years after primary diagnosis. During the intervening years between initial treatment and relapse, occult cancers are maintained in an apparent state of dormancy that is poorly understood. In this study, we applied a probabilistic mathematical model to long-term follow-up studies of postresection patients to investigate the factors involved in mediating breast cancer dormancy. Our results suggest that long-term dormancy is maintained most often by just one growth-restricted dangerous micrometastasis. Analysis of the empirical data by Approximate Bayesian Computation indicated that patients in dormancy have between 1 and 5 micrometastases at 10 years postresection, when they escape growth restriction with a half-life of &lt;69 years and are &gt;0.4 mm in diameter. Before resection, primary tumors seed at most an average of 6 dangerous micrometastases that escape from growth restriction with a half-life of at least 12 years. Our findings suggest that effective preventive treatments will need to eliminate these small numbers of micrometastases, which may be preangiogenic and nonvascularized until they switch to growth due to one oncogenic mutation or tumor suppressor gene inactivation. In summary, breast cancer dormancy seems to be maintained by small numbers of sizeable micrometastases that escape from growth restriction with a half-life exceeding 12 years. Cancer Res; 70(11); 4310–7. ©2010 AACR.
Downregulation of MicroRNA miR-520h by E1A Contributes to Anticancer Activity
Authors: Su Jen-Liang , Chen Poshen B. , Chen Ya-Huey , Chen Shang-Chih , Chang Yi-Wen , Jan Yi-Hua , Cheng Xiaoyun , Hsiao Michael , Hung Mien-Chie 
Published: May 2010

AbstractThe leading cause of death in cancer patients is cancer metastasis, for which there is no effective treatment. MicroRNAs (miRNA) have been shown to play a significant role in cancer metastasis through regulation of gene expression. The adenovirus type 5 E1A (E1A) is associated with multiple tumor-suppressing activities including the inhibition of metastasis, and E1A gene therapies have been tested in several clinical trials. However, the mechanisms involved in E1A-mediated tumor-suppressing activities are not yet completely defined. Here, we showed that E1A downregulated the expression of the miRNA miR-520h, which was critical for E1A-mediated cancer cell mobility and in vitro invasion activity. In addition, we identified a signal cascade, namely, E1A→miRNA-520h→PP2A/C→IκB kinase→NF-κB→Twist, in which E1A inhibited the expression of Twist through downregulation of miR-520h and the signal cascade. Our results indicated a functional link between miR-520h and tumorigenicity/invasive ability and provided a new insight into the role of E1A-mediated miRNA regulation in tumor suppression. Therefore, the results identified a new cascade of E1A-mediated tumor suppression activity via downregulation of miRNA-520h expression. Cancer Res; 70(12); 5096–108. ©2010 AACR.
PTPL1/PTPN13 Regulates Breast Cancer Cell Aggressiveness through Direct Inactivation of Src Kinase
Authors: Glondu-Lassis Murielle , Dromard Mathilde , Lacroix-Triki Magali , Nirdé Philippe , Puech Carole , Knani Dora , Chalbos Dany , Freiss Gilles 
Published: May 2010

Abstract
The protein tyrosine phosphatase PTPL1/PTPN13, the activity of which is decreased through allelic loss, promoter methylation, or somatic mutations in some tumors, has been proposed as a tumor suppressor gene. Moreover, our recent clinical study identified PTPL1 expression level as an independent prognostic indicator of a favorable outcome for patients with breast cancer. However, how PTPL1 can affect tumor aggressiveness has not been characterized. Here, we first show that PTPL1 expression, assessed by immunohistochemistry, is decreased in breast cancer and metastasis specimens compared with nonmalignant tissues. Second, to evaluate whether PTPL1 plays a critical role in breast cancer progression, RNA interference experiments were performed in poorly tumorigenic MCF-7 breast cancer cells. PTPL1 inhibition drastically increased tumor growth in athymic mice and also enhanced several parameters associated with tumor progression, including cell proliferation on extracellular matrix components and cell invasion. Furthermore, the inhibition of Src kinase expression drastically blocked the effects of PTPL1 silencing on cell growth. In PTPL1 knockdown cells, the phosphorylation of Src on tyrosine 419 is increased, leading to the activation of its downstream substrates Fak and p130cas. Finally, substrate-trapping experiments revealed that Src tyrosine 419 is a direct target of the phosphatase. Thus, by identification of PTPL1 as the first phosphatase able to inhibit Src through direct dephosphorylation in intact cells, we presently describe a new mechanism by which PTPL1 inhibits breast tumor aggressiveness. Cancer Res; 70(12); 5116–26. ©2010 AACR.
βIII-Tubulin Is a Multifunctional Protein Involved in Drug Sensitivity and Tumorigenesis in Non–Small Cell Lung Cancer
Authors: McCarroll Joshua A. , Gan Pei Pei , Liu Marjorie , Kavallaris Maria 
Published: May 2010

Abstract
Advanced non–small cell lung cancer (NSCLC) has a dismal prognosis. βIII-Tubulin, a protein highly expressed in neuronal cells, is strongly associated with drug-refractory and aggressive NSCLC. To date, the role of this protein in in vivo drug resistance and tumorigenesis has not been determined. NSCLC cells stably expressing βIII-tubulin short hairpin RNA displayed reduced growth and increased chemotherapy sensitivity when compared with control clones. In concordance with these results, stable suppression of βIII-tubulin reduced the incidence and significantly delayed the growth of tumors in mice relative to controls. Our findings indicate that βIII-tubulin mediates not only drug sensitivity but also the incidence and progression of lung cancer. βIII-Tubulin is a cellular survival factor that, when suppressed, sensitizes cells to chemotherapy via enhanced apoptosis induction and decreased tumorigenesis. Findings establish that upregulation of a neuronal tubulin isotype is a key contributor to tumor progression and drug sensitivity in lung adenocarcinoma. Cancer Res; 70(12); 4995–5003. ©2010 AACR.
Histone Methyltransferase Gene SETD2 Is a Novel Tumor Suppressor Gene in Clear Cell Renal Cell Carcinoma
Authors: Duns Gerben , van den Berg Eva , van Duivenbode Inge , Osinga Jan , Hollema Harry , Hofstra Robert M.W. , Kok Klaas 
Published: May 2010

Abstract
Sporadic clear cell renal cell carcinoma (cRCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3, with a hotspot for copy number loss in the 3p21 region. We applied a method called “gene identification by nonsense-mediated mRNA decay inhibition” to a panel of 10 cRCC cell lines with 3p21 copy number loss to identify biallelic inactivated genes located at 3p21. This revealed inactivation of the histone methyltransferase gene SETD2, located on 3p21.31, as a common event in cRCC cells. SETD2 is nonredundantly responsible for trimethylation of the histone mark H3K36. Consistent with this function, we observed loss or a decrease of H3K36me3 in 7 out of the 10 cRCC cell lines. Identification of missense mutations in 2 out of 10 primary cRCC tumor samples added support to the involvement of loss of SETD2 function in the development of cRCC tumors. Cancer Res; 70(11); 4287–91. ©2010 AACR.
Mechanism by Which Mcl-1 Regulates Cancer-Specific Apoptosis Triggered by mda-7/IL-24, an IL-10–Related Cytokine
Authors: Dash Rupesh , Richards Joanna E. , Su Zhao-zhong , Bhutia Sujit K. , Azab Belal , Rahmani Mohamed , Dasmahapatra Girija , Yacoub Adly , Dent Paul , Dmitriev Igor P. , Curiel David T. , Grant Steven , Pellecchia Maurizio , Reed John C. , Sarkar Devanand , Fisher Paul B. 
Published: May 2010

Abstract
Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a cytokine belonging to the IL-10 family, selectively induces apoptosis in cancer cells without harming normal cells by promoting an endoplasmic reticulum (ER) stress response. The precise molecular mechanism by which the ER stress response culminates in cell death requires further clarification. The present study shows that in prostate carcinoma cells, the mda-7/IL-24–induced ER stress response causes apoptosis by translational inhibition of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1). Forced expression of Mcl-1 blocked mda-7/IL-24 lethality, whereas RNA interference or gene knockout of Mcl-1 markedly sensitized transformed cells to mda-7/IL-24. Mcl-1 downregulation by mda-7/IL-24 relieved its association with the proapoptotic protein Bak, causing oligomerization of Bak and leading to cell death. These observations show the profound role of the Bcl-2 protein family member Mcl-1 in regulating cancer-specific apoptosis induced by this cytokine. Thus, our studies provide further insights into the molecular mechanism of ER stress–induced cancer-selective apoptosis by mda-7/IL-24. As Mcl-1 is overexpressed in the majority of prostate cancers, mda-7/IL-24 might provide an effective therapeutic for this disease. Cancer Res; 70(12); 5034–45. ©2010 AACR.
Control of Tumorigenesis and Chemoresistance by the DEK Oncogene
Authors: Riveiro-Falkenbach Erica , Soengas María S. 
Published: May 2010

Abstract
Slight modifications of chromatin dynamics can translate into small- and large-scale changes in DNA replication and DNA repair. Similarly, promoter usage and accessibility are tightly dependent on chromatin architecture. Consequently, it is perhaps not surprising that factors controlling chromatin organization are frequently deregulated (directly or indirectly) in cancer cells. DEK is emerging as a novel class of DNA topology modulators that can be both targets and effectors of protumorigenic events. The locus containing DEK at chromosome 6p22.3 is amplified or reorganized in multiple cancer types. In addition, DEK can be subject to a variety of tumor-associated transcriptional and post-translational modifications. In turn, DEK can favor cell transformation, at least in part by inhibiting cell differentiation and premature senescence. More recently, DEK has also been linked to the resistance of malignant cells to apoptotic inducers. Interestingly, a fraction of DEK can also bind RNA and affect alternative splicing, further illustrating the pleiotropic roles that this protein may exert in cancer cells. Here we will summarize the current literature about the regulation and function(s) of DEK as a proto-oncogene. In addition, the translational relevance of DEK as a putative diagnostic marker and candidate for drug development will be discussed. Clin Cancer Res; 16(11); 2932–8. ©2010 AACR.
A Phase I Study of 5-Fluorouracil/Leucovorin and Arsenic Trioxide for Patients with Refractory/Relapsed Colorectal Carcinoma
Authors: Ardalan Bach , Subbarayan Pochi R. , Ramos Yipsel , Gonzalez Michael , Fernandez Anthony , Mezentsev Dmitry , Reis Isildinha , Duncan Robert , Podolsky Lisa , Lee Kelvin , Lima Mayra , Ganjei-Azar Parvin 
Published: May 2010

Abstract
Purpose: This Phase I study was designed to determine a safe combination dose of 5-fluorouracil (5-FU) and arsenic trioxide (ATO) to treat 5-FU–resistant relapsed/refractory colorectal cancer patients. We studied the effect of ATO in the downregulation of thymidylate synthase (TS) in peripheral blood mononuclear cells and in tumor biopsies.
Experimental Design: ATO was administered for 5 consecutive days during the first week and twice during weeks 2 to 3 and once on week 4. 5-FU/leucovorin (LV) was administered on days 8, 15, and 22. A modified accelerated titration design was used. 5-FU was dose escalated first followed by a planned dose increase for ATO.
Results: No dose-limiting toxicities were seen in seven patients who received 0.15 mg/kg ATO; grade 3 toxicities were as follows: neutropenia 1, diarrhea 1, and bowel obstruction 1. In patients receiving 0.20 mg/kg ATO, grade 3 toxicities were QTc prolongation 1, fatigue 4, alkaline phosphatase elevation 2, diarrhea 2, and peripheral edema 1. TS gene expression in peripheral blood mononuclear cell decreased in all patients. Eight tumors were biopsied, four showed TS downregulation, three showed upregulations, and one did not change. Estimated median progression-free survival and overall survival were 3.1 and 13.9 months, respectively. In patients who showed TS increase or no change versus TS reduction, estimated median progression-free survival was 2.6 versus 7.9 months (P = 0.188) and overall survival was 8.6 versus 11.7 months (P = 0.44), respectively.
Conclusions: Thus, we determined 0.20 mg/kg ATO, 2,600 mg/m2 5-FU, and 500 mg/m2 leucovorin (LV) to be the recommended phase II dose. Clin Cancer Res; 16(11); 3019–27. ©2010 AACR.