bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bystander effect of vinorelbine alters antitumor immune response
Authors: Thomas‐Schoemann Audrey , Lemare François , Mongaret Céline , Bermudez Elisabeth , Chéreau Christiane , Nicco Carole , Dauphin Alain , Weill Bernard , Goldwasser François , Batteux Frédéric , Alexandre Jérôme 
Published: December 2010

AbstractThe bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells. In this study, we showed that it could also affect immune cells surrounding the tumor and interfere with the antitumor immune response. We observed that the exposure of human lung cancer cells A549 to vinorelbine induced a BE on neighboring human peripheral blood mononuclear cells (PBMCs) in vitro and on mice splenocytes in vivo. In vitro, the number of PBMCs killed because of their coculture with vinorelbine‐pretreated A549 cells was 33% higher than those killed by A549 control cells (p = 0.003). In addition, we showed that when vinorelbine‐pretreated A549 cells were injected into immunocompetent mice, splenocyte proliferation ex vivo toward tumor cells decreased by 27% compared with that seen in mice injected with untreated A549 cells (p = 0.03). Finally, in vivo experiment in A549 tumor bearing nude mice showed that adoptive transfer of A549 immune splenocytes was not able to delay tumor growth when vinorelbine‐pretreated A549 cells were used for immunization. Inhibition of the BE by the nitric oxide synthase inhibitor, N(G)‐nitro‐L‐arginine methyl ester, and the superoxide dismutase mimic, mangafodipir, suggested that it was mediated by oxidative and nitrosative stress. In conclusion, exposure of cancer cells to vinorelbine alters the antitumor immune response through a BE mediated by cellular oxidative and nitrosative stress. Our results offer new prospects for using oxidative stress modulators to restore the antitumor immune response in patients treated with anticancer agents.
A microdosing approach for characterizing formation and repair of carboplatin–DNA monoadducts and chemoresistance
Authors: Henderson Paul T. , Li Tao , He Miaoling , Zhang Hongyong , Malfatti Michael , Gandara David , Grimminger Peter P. , Danenberg Kathleen D. , Beckett Laurel , de Vere White Ralph W. , Turteltaub Kenneth W. , Pan Chong‐Xian 
Published: December 2010

AbstractFormation and repair of platinum (Pt)‐induced DNA adducts is a critical step in Pt drug‐mediated cytotoxicity. Measurement of Pt–DNA adduct kinetics in tumors may be useful for better understanding chemoresistance and therapeutic response. However, this concept has yet to be rigorously tested because of technical challenges in measuring the adducts at low concentrations and consistent access to sufficient tumor biopsy material. Ultrasensitive accelerator mass spectrometry was used to detect [14C]carboplatin–DNA monoadducts at the attomole level, which are the precursors to Pt–DNA crosslink formation, in six cancer cell lines as a proof‐of‐concept. The most resistant cells had the lowest monoadduct levels at all time points over 24 hr. [14C]Carboplatin “microdoses” (1/100th the pharmacologically effective concentration) had nearly identical adduct formation and repair kinetics compared to therapeutically relevant doses, suggesting that the microdosing approach can potentially be used to determine the pharmacological effects of therapeutic treatment. Some of the possible chemoresistance mechanisms were also studied, such as drug uptake/efflux, intracellular inactivation and DNA repair in selected cell lines. Intracellular inactivation and efficient DNA repair each contributed significantly to the suppression of DNA monoadduct formation in the most resistant cell line compared to the most sensitive cell line studied (p < 0.001). Nucleotide excision repair (NER)‐deficient and ‐proficient cells showed substantial differences in carboplatin monoadduct concentrations over 24 hr that likely contributed to chemoresistance. The data support the utility of carboplatin microdosing as a translatable approach for defining carboplatin–DNA monoadduct formation and repair, possibly by NER, which may be useful for characterizing chemoresistance in vivo.
LRIG1 and the liar paradox in prostate cancer: A study of the expression and clinical significance of LRIG1 in prostate cancer
Authors: Thomasson Marcus , Wang Baofeng , Hammarsten Peter , Dahlman Anna , Persson Jenny Liao , Josefsson Andreas , Stattin Pär , Granfors Torvald , Egevad Lars , Henriksson Roger , Bergh Anders , Hedman Håkan 
Published: December 2010

AbstractThe course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine‐rich repeats and immunoglobulin‐like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T‐stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer‐specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances.
Identification of candidate predisposing copy number variants in familial and early‐onset colorectal cancer patients
Authors: Venkatachalam Ramprasath , Verwiel Eugène T.P. , Kamping Eveline J. , Hoenselaar Eveline , Görgens Heike , Schackert Hans K. , van Krieken J. Han J.M. , Ligtenberg Marjolijn J.L. , Hoogerbrugge Nicoline , van Kessel Ad Geurts , Kuiper Roland P. 
Published: December 2010

AbstractIn the majority of colorectal cancers (CRCs) under clinical suspicion for a hereditary cause, the disease‐causing genetic factors are still to be discovered. To identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite‐stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome‐wide copy number profiling using high‐resolution SNP arrays on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in six patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1, and the breakpoint cluster region gene BCR. In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa‐mir‐491/KIAA1797 and hsa‐mir‐646/AK309218. None of these CNVs has previously been reported in relation to CRC predisposition in humans, nor were they encountered in large control cohorts (>1,600 unaffected individuals). Since several of these newly identified candidate genes may be functionally linked to CRC development, our results illustrate the potential of this approach for the identification of novel candidate genes involved in CRC predisposition.
Racial/ethnic differences in colorectal cancer risk: The multiethnic cohort study
Authors: Ollberding Nicholas J. , Nomura Abraham M.Y. , Wilkens Lynne R. , Henderson Brian E. , Kolonel Laurence N. 
Published: December 2010

AbstractIncidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age‐adjusted variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Americans, Latinos, Native Hawaiians and whites participating in the Multiethnic Cohort Study. Over a median follow‐up period of 10.7 years, 2,564 incident cases of colorectal cancer were identified through surveillance, epidemiology and end result tumor registry linkages in Hawaii and California. Multivariable‐adjusted Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for each ethnic group compared to whites. After accounting for known/suspected risk factors, Japanese Americans (men, RR = 1.27, 95% CI = 1.09–1.48; women, RR = 1.49, 95% CI = 1.24–1.78) and African American women (RR = 1.48, 95% CI = 1.23–1.79) remained at increased risk of colorectal cancer relative to whites; African American and Japanese American women were also at increased risk of advanced disease compared to whites. In site‐specific analyses, after multivariable adjustment, African Americans (both sexes) and Japanese American women remained at increased risk for colon cancer, and Japanese Americans (both sexes) and Native Hawaiian men for rectal cancer compared to whites. The results of our study suggest that differences in the distribution of known/suspected risk factors account for only a modest proportion of the ethnic variation in colorectal cancer risk and that other factors, possibly including genetic susceptibility, are important contributors to the observed disparities in incidence.
MicroRNA expression profiling in human Barrett's carcinogenesis
Authors: Fassan Matteo , Volinia Stefano , Palatini Jeff , Pizzi Marco , Baffa Raffaele , De Bernard Marina , Battaglia Giorgio , Parente Paola , Croce Carlo M. , Zaninotto Giovanni , Ancona Ermanno , Rugge Massimo 
Published: December 2010

AbstractBarrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low‐grade intraepithelial neoplasia, 5 with high‐grade intra‐epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real‐time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long‐segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.
The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy
Authors: Yhim Ho‐Young , Lee Na‐Ri , Song Eun‐Kee , Kwak Jae‐Yong , Lee Soo Teik , Kim Jong Hun , Kim Jung‐Soo , Park Ho Sung , Chung Ik‐Joo , Shim Hyun‐Jeong , Hwang Jun‐Eul , Kim Hyeong Rok , Nam Taek‐Keun , Park Moo‐Rim , Shim Hyeok , Park Hyo Sook , Kim Hee Sun , Yim Chang‐Yeol 
Published: December 2010

AbstractThe prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin‐embedded tumor tissues. The median age was 65 years (range, 44–90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N‐positive). Thirty‐five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16‐positive). Thirty‐nine (83.0%) patients were positive for p16. After median follow‐up of 51.7 months (range, 5.1–136.0 months), HPV16‐positive group had significantly better 4‐year progression‐free survival (PFS, 63.1% vs. 15.6%, p < 0.001) and overall survival (84.6% vs. 39.8%, p = 0.008) than HPV genotype 16 negative (HPV16‐negative) group. Patients with p16‐positive tumor also had a better 4‐year PFS (52.5% vs. 25.0%, p = 0.014) than those with p16‐negative tumor. In multivariate analysis for PFS, N‐positive and HPV16‐negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco‐regional failure was statistically superior in HPV16‐positive over HPV16‐negative groups (p = 0.006), but time to systemic failure was not different (p = 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted.
Dermatofibrosarcoma protuberans‐derived fibrosarcoma: Clinical history, biological profile and sensitivity to imatinib
Authors: Stacchiotti Silvia , Pedeutour Florence , Negri Tiziana , Conca Elena , Marrari Andrea , Palassini Elena , Collini Paola , Keslair Frederique , Morosi Carlo , Gronchi Alessandro , Pilotti Silvana , Casali Paolo G. 
Published: December 2010

AbstractDermatofibrosarcoma Protuberans (DFSP) carries a translocation resulting in the COL1A1/PDGFB fusion‐gene, responsible for platelet derived growth factor beta receptor (PDGFRB) activation. Fibrosarcomatous (FS) transformation in DFSP rarely occur. The fusion‐gene and PDGFRB expression/activation pattern and imatinib role in DFSP‐derived FS is less defined. We reviewed all consecutive patients operated for localized DFSP at our institution from 1994 to 2009, selecting cases with FS component. We also reviewed patients treated with imatinib for advanced FS‐DFSP over the same period. When cryopreserved material was available, biochemical/molecular analyses were performed. Of 275 DFSPs, 13 (4.7%) showed a FS component. Fifteen percent of these patients developed metastases, one to the brain. Four patients with DFSP‐derived FS received imatinib, with a Response Evaluation Criteria in Solid Tumor Partial Response. Response was followed by early secondary progression in two. One died for brain metastases. Three patients underwent surgery after imatinib. The fusion‐gene was detected in all cases in both the classical and FS component, before and after imatinib. PDGFRB expression/activation was confirmed in all cases. mTOR was switched‐off, despite the phosphorylation of its effectors. However, a strong phosphorylation of S6 and 4EBP1 was restricted to the FS component. In conclusion, DFSP‐derived FS maintains the fusion‐gene, being sensitive to imatinib. However, responses are short‐lasting. Secondary resistance to imatinib is not related to PDGFRB.
Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography
Authors: Frost Michelle L , Siddique Musib , Blake Glen M , Moore Amelia EB , Schleyer Paul J , Dunn Joel T , Somer Edward J , Marsden Paul K , Eastell Richard , Fogelman Ignac 
Published: December 2010

Abstract
Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18F-fluoride plasma clearance (Ki) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine Ki values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine Ki values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k3/[k2 + k3]), which increased by 23% (p = .0006). In contrast to Ki, spine SUVs increased by only 3% (p = .84). The discrepancy between changes in Ki and SUVs was explained by a 20% decrease in 18F− plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18F− PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. © 2011 American Society for Bone and Mineral Research.
Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones
Authors: Ominsky Michael S , Li Chaoyang , Li Xiaodong , Tan Hong L , Lee Edward , Barrero Mauricio , Asuncion Franklin J , Dwyer Denise , Han Chun-Ya , Vlasseros Fay , Samadfam Rana , Jolette Jacquelin , Smith Susan Y , Stolina Marina , Lacey David L , Simonet William S , Paszty Chris , Li Gang , Ke Hua Z 
Published: December 2010

Abstract
Therapeutic enhancement of fracture healing would help to prevent the occurrence of orthopedic complications such as nonunion and revision surgery. Sclerostin is a negative regulator of bone formation, and treatment with a sclerostin monoclonal antibody (Scl-Ab) results in increased bone formation and bone mass in animal models. Our objective was to investigate the effects of systemic administration of Scl-Ab in two models of fracture healing. In both a closed femoral fracture model in rats and a fibular osteotomy model in cynomolgus monkeys, Scl-Ab significantly increased bone mass and bone strength at the site of fracture. After 10 weeks of healing in nonhuman primates, the fractures in the Scl-Ab group had less callus cartilage and smaller fracture gaps containing more bone and less fibrovascular tissue. These improvements at the fracture site corresponded with improvements in bone formation, bone mass, and bone strength at nonfractured cortical and trabecular sites in both studies. Thus the potent anabolic activity of Scl-Ab throughout the skeleton also was associated with an anabolic effect at the site of fracture. These results support the potential for systemic Scl-Ab administration to enhance fracture healing in patients. © 2011 American Society for Bone and Mineral Research.
Discrepancies between community violence exposure and perceived neighborhood violence
Authors: Cammack Nicole L. , Lambert Sharon F. , Ialongo Nicholas S. 
Published: December 2010

AbstractCommunity violence exposure (CVE) has been identified as a significant public health concern given its association with numerous mental health problems. Perceptions of neighborhood violence (PNV) also may adversely affect youth adjustment. In recognition that PNV may differ from individuals own experience of CVE, the current study utilized latent class analysis to examine the degree and consequences of consistency and discrepancy in adolescents community violence exposure and PNV. Participants included an epidemiologically‐defined community sample of 456 African American adolescents (52% male; mean age=11.77). Results revealed three groups of youth: high CVE/high PNV, low CVE/low PNV, and low CVE/high PNV. Longitudinal analyses suggest that a discrepancy between CVE and PNV is important for understanding depressive and anxious symptoms among urban African American youth. Implications for intervention are discussed. © 2010 Wiley Periodicals, Inc.
Extraction of naringin from pomelo peels as dihydrochalcone's precursor
Authors: Tang Dong‐Mei , Zhu Chun‐Feng , Zhong Shi‐An , Zhou Ming‐Da 
Published: December 2010

AbstractA new method for the separation of naringin from pomelo peels was investigated by using ultrasonic‐assisted extraction and macroporous resin purification technology. The ultrasonic extraction efficiency was dependent on agent's concentration, ratio of sample and solvent and ultrasonic time. Several parameters of macroporous resin‐purified process, including resin selection, initial concentration, concentration of eluted agent and pH, were optimized. The experimental results showed that the naringin content in the mature pomelo peels was 2.20% and purification rate of naringin was 77.26% under optimum conditions of purification. The structure of synthetic naringin dihydrochalcone was determined by a series of spectroscopic methods, such as UV, NMR and MS.
Influence of the FID and off‐resonance effects in dense MRI
Authors: Haraldsson Henrik , Sigfridsson Andreas , Sakuma Hajime , Engvall Jan , Ebbers Tino 
Published: December 2010

AbstractAccurate functional measurement in cardiovascular diseases is important as inaccuracy may compromise diagnostic decisions. Cardiac function can be assessed using displacement encoding with stimulated echoes, resulting in three signal components. The free induction decay (FID), arising from spins undergoing T1‐relaxation, is not displacement encoded and impairs the displacement acquired. Techniques for suppressing the FID exist; however, a residual will remain. The effect of the residual is difficult to distinguish and investigate in vitro and in vivo. In this work, the influence of the FID as well as of off‐resonance effects is evaluated by altering the phase of the FID in relation to the stimulated echo. The results show that the FID and off‐resonance effects can impair the accuracy of the displacement measurement acquired. The influence of the FID can be avoided by using an encoded reference. We therefore recommend the assessment of this influence of the FID for each displacement encoding with stimulated echoes protocol. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.