bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory function and bronchial responsiveness among industrial workers exposed to different classes of occupational agents: a study from Algeria
Authors: Ould-Kadi Farid , Nawrot Tim S , Hoet Peter H , Nemery Benoit 
Published: October 2007

AbstractOccupational exposures play a role in the onset of several chronic airway diseases. We investigated, in a cross-sectional study, lung function parameters and bronchial hyper-responsiveness to histamine in workers exposed to different airborne compounds.The study group totalled 546 male subjects of whom 114 were exposed to welding fumes, 106 to solvents, 107 to mineral dust, 97 to organic dust and 123 without known exposure to airway irritants. A questionnaire was administered and spirometry and bronchial responsiveness to histamine were assessed by one observer, in the morning before work to prevent effects of acute exposure.The mean (SD) age of the participants was 39.3 (7.8) years, with a mean duration of employment of 13.8 (6.6) years. Both before and after adjustment for smoking status, forced expiratory volume in 1 second (FEV1, expressed as % predicted) was lower in welders -4.0% (95% confidence interval [CI], -6.3 to -1.8; p = 0.01) and workers exposed to solvents -5.6% (CI: -7.9 to -3.3; p = 0.0009) than in control subjects. Furthermore, solvent workers had an odds ratio of 3.43 (95% CI: 1.09–11.6; p = 0.037) for bronchial hyperresponsiveness compared with the reference group.The higher prevalence of bronchial hyperresponsiveness in solvent workers adds to the growing body of evidence of adverse respiratory effects of occupational solvent exposure. These results point to the necessity of preventive measures in solvent workers to avoid these adverse respiratory effects.
Intrinsic genetic characteristics determine tumor-modifying capacity of fibroblasts: matrix metalloproteinase-3 5A/5A genotype enhances breast cancer cell invasion
Authors: Holliday Deborah L , Hughes Simon , Shaw Jacqueline A , Walker Rosemary A , Jones J Louise 
Published: October 2007

Abstract
Background
Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion.

Methods
Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided.

Results
Tumor-derived fibroblasts promoted higher levels of invasion than normal fibroblasts (p = 0.041). When IPC was related to genotype, higher levels of IPC were generated by tumor fibroblasts with the high-expressing MMP-3 5A/5A genotype compared with the 5A/6A and 6A/6A genotypes (p = 0.05 and 0.07, respectively), and this was associated with enhanced MMP-3 release. The functional importance of MMP-3 was demonstrated by enhanced invasion in the presence of recombinant MMP-3, whereas reduction occurred in the presence of a specific MMP-3 inhibitor. An inverse relationship was demonstrated between fibroblast IPC and the high-expressing MMP-1 genotype (p = 0.031), but no relationship was seen with MMP-9 SNP status. In contrast, normal fibroblasts showed no variation in IPC in relation to MMP genotype, with MMP-3 5A/5A fibroblasts exhibiting significantly lower levels of IPC than their tumor-derived counterparts (p = 0.04).

Conclusion
This study has shown that tumor-derived fibroblasts exhibit higher levels of IPC than normal fibroblasts and that the MMP-3 5A/5A genotype contributes to this through enhanced MMP-3 release. Despite a high-expressing genotype, normal fibroblasts do not exhibit higher IPC or enhanced MMP release. This suggests that more complex changes occur in tumor-derived fibroblasts, enabling full expression of the MMP SNP genotype and these possibly are epigenetic in nature. The results do suggest that, in women with breast cancer, a high-expressing MMP-3 genotype may promote tumor progression more effectively.
MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype
Authors: Blenkiron Cherie , Goldstein Leonard D , Thorne Natalie P , Spiteri Inmaculada , Chin Suet-Feung , Dunning Mark J , Barbosa-Morais Nuno L , Teschendorff Andrew E , Green Andrew R , Ellis Ian O , Tavaré Simon , Caldas Carlos , Miska Eric A 
Published: October 2007

Abstract
Background
MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression.

Results
Here we report the analysis of miRNA expression in 93 primary human breast tumors, using a bead-based flow cytometric miRNA expression profiling method. Of 309 human miRNAs assayed, we identify 133 miRNAs expressed in human breast and breast tumors. We used mRNA expression profiling to classify the breast tumors as luminal A, luminal B, basal-like, HER2+ and normal-like. A number of miRNAs are differentially expressed between these molecular tumor subtypes and individual miRNAs are associated with clinicopathological factors. Furthermore, we find that miRNAs could classify basal versus luminal tumor subtypes in an independent data set. In some cases, changes in miRNA expression correlate with genomic loss or gain; in others, changes in miRNA expression are likely due to changes in primary transcription and or miRNA biogenesis. Finally, the expression of DICER1 and AGO2 is correlated with tumor subtype and may explain some of the changes in miRNA expression observed.

Conclusion
This study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer. Furthermore, we demonstrate that bead-based flow cytometric miRNA expression profiling might be a suitable platform to classify breast cancer into prognostic molecular subtypes.
High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer
Authors: Chin Suet F , Teschendorff Andrew E , Marioni John C , Wang Yanzhong , Barbosa-Morais Nuno L , Thorne Natalie P , Costa Jose L , Pinder Sarah E , van de Wiel Mark A , Green Andrew R , Ellis Ian O , Porter Peggy L , Tavaré Simon , Brenton James D , Ylstra Bauke , Caldas Carlos 
Published: October 2007

Abstract
Background
The characterization of copy number alteration patterns in breast cancer requires high-resolution genome-wide profiling of a large panel of tumor specimens. To date, most genome-wide array comparative genomic hybridization studies have used tumor panels of relatively large tumor size and high Nottingham Prognostic Index (NPI) that are not as representative of breast cancer demographics.

Results
We performed an oligo-array-based high-resolution analysis of copy number alterations in 171 primary breast tumors of relatively small size and low NPI, which was therefore more representative of breast cancer demographics. Hierarchical clustering over the common regions of alteration identified a novel subtype of high-grade estrogen receptor (ER)-negative breast cancer, characterized by a low genomic instability index. We were able to validate the existence of this genomic subtype in one external breast cancer cohort. Using matched array expression data we also identified the genomic regions showing the strongest coordinate expression changes ('hotspots'). We show that several of these hotspots are located in the phosphatome, kinome and chromatinome, and harbor members of the 122-breast cancer CAN-list. Furthermore, we identify frequently amplified hotspots on 8q22.3 (EDD1, WDSOF1), 8q24.11-13 (THRAP6, DCC1, SQLE, SPG8) and 11q14.1 (NDUFC2, ALG8, USP35) associated with significantly worse prognosis. Amplification of any of these regions identified 37 samples with significantly worse overall survival (hazard ratio (HR) = 2.3 (1.3-1.4) p = 0.003) and time to distant metastasis (HR = 2.6 (1.4-5.1) p = 0.004) independently of NPI.

Conclusion
We present strong evidence for the existence of a novel subtype of high-grade ER-negative tumors that is characterized by a low genomic instability index. We also provide a genome-wide list of common copy number alteration regions in breast cancer that show strong coordinate aberrant expression, and further identify novel frequently amplified regions that correlate with poor prognosis. Many of the genes associated with these regions represent likely novel oncogenes or tumor suppressors.
Access to Pediatric Cancer Care by Age, Race, and Diagnosis, and Outcomes of Cancer Treatment in Pediatric and Adolescent Patients in the State of Georgia
Authors: Howell Della L. , Ward Kevin C. , Austin Harland D. , Young John L. , Woods William G. 
Published: October 2007

Purpose There have been concerns among pediatric oncologists that adolescent and minority patients are not getting adequate access to care. This study examines access to cancer care and survival outcomes based on age, race, and type of cancer in patients in Georgia. Patients and Methods We performed a retrospective review of 1,751 cancer patients aged 0 to 19 years, diagnosed between 1998 and 2002, in the Georgia Comprehensive Cancer Registry, which identified patients who were treated at one of five Georgia pediatric cancer centers (Children's Oncology Group [COG] members) at any point in their treatment. Data were further analyzed for age at diagnosis, race, county of residence, and 5-year survival. Results Eighty-seven percent of patients aged 0 to 14 years and 36% of those aged 15 to 19 years were treated at a COG institution. Twenty-five percent of all patients were of African descent, with 75.4% of black versus 70.3% of white patients (age 0 to 19 years) treated at a COG institution (P < .01); 97.1% of other minorities were treated at a COG institution (P < .05). The 5-year actuarial survival rates for more pediatric-specific cancers were significantly lower in all leukemias (75.1% v 46.4%; P = .0015), and acute lymphoblastic leukemia specifically (86.3% v 53.3%; P < .05) for patients not treated at a COG institution. Actuarial survival rates were much lower for blacks than whites in all cancers as a whole (70% v 82%; P < .001) and for many specific subtypes. Conclusion Adolescent-aged patients are less likely to be referred to a COG institution, potentially exposing them to worse outcomes in some cancer subtypes. Reassuringly, minority populations are receiving adequate access to pediatric cancer care; unfortunately their survival rates are lower.
Pharmacogenetic Assessment of Toxicity and Outcome After Platinum Plus Taxane Chemotherapy in Ovarian Cancer: The Scottish Randomised Trial in Ovarian Cancer
Authors: Marsh Sharon , Paul Jim , King Cristi R. , Gifford Gillian , McLeod Howard L. , Brown Robert 
Published: October 2007

Purpose Standard therapy for advanced ovarian cancer consists of a platinum agent in combination with a taxane, which has a 5-year survival rate of approximately 45%. The large individual variability for ovarian cancer patients in both outcome and toxicity risk from chemotherapy makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect. Patients and Methods We assessed 27 selected polymorphisms based on previously described associations or putative functional effects in 16 key genes from pathways that may influence cellular sensitivity to taxanes (ABCB1, ABCC1, ABCC2, ABCG2, CDKN1A, CYP1B1, CYP2C8, CYP3A4, CYP3A5, MAPT, and TP53) and platinum (ABCC2, ABCG2, ERCC1, ERCC2, GSTP1, MPO, and XRCC1) using polymerase chain reaction and Pyrosequencing in 914 ovarian cancer patients from the Scottish Randomised Trial in Ovarian Cancer phase III trial who were treated at presentation with carboplatin and taxane regimens after cytoreductive surgery. Results No reproducible significant associations between genotype and outcome or toxicity were found for any of the genes analyzed. Previously reported genotype associations could not be replicated in this large study of a well-defined patient population within one specific clinical trial. Conclusion There are no clear candidates for taxane/platinum pharmacogenetic markers. This study highlights the need for validation of putative genetic markers in large, well-defined clinical sample sets.
Hepatic Resection After Rescue Cetuximab Treatment for Colorectal Liver Metastases Previously Refractory to Conventional Systemic Therapy
Authors: Adam René , Aloia Thomas , Lévi Francis , Wicherts Dennis A. , de Haas Robbert J. , Paule Bernard , Bralet Marie-Pierre , Bouchahda Mohamed , Machover David , Ducreux Michel , Castagne Vincent , Azoulay Daniel , Castaing Denis 
Published: October 2007

Purpose In patients with unresectable colorectal liver metastases (CLM) resistant to first-line chemotherapy, the impact of cetuximab therapy on resectability is unknown. This study was performed to determine the post-cetuximab resectability rate and to examine postoperative outcomes for these heavily pretreated patients. Patients and Methods From February 2004 to April 2006, we evaluated 151 patients with unresectable CLM resistant to initial chemotherapy and subsequently treated with systemic cetuximab. Resectability rates, patient outcomes, and tumoral and nontumoral liver pathology were assessed. Results A total of 27 patients underwent surgery after a median of six cycles of cetuximab + irinotecan (20 of 27), oxaliplatin (four of 27), or both (one of 27). Eighteen patients (67%) had experienced treatment failure after at least two lines of chemotherapy before cetuximab. Twenty-five of the 27 patients who had surgery underwent hepatectomy: nine of 133 patients who were treated completely at our institution (resectability rate, 7%) and 16 of 18 patients who were referred from other institutions after systemic cetuximab therapy. Postoperative mortality was 3.7% (one of 27), with a complication rate of 50%. Histopathologic liver abnormalities were found in nine patients (36%), without specific lesions attributable to cetuximab. After median follow-up of 16 months, 23 of 25 patients who underwent resection (92%) were alive, and 10 patients (40%) were disease free. Median overall (OS) and progression-free survival (PFS) from initiation of cetuximab therapy were 20 and 13 months, respectively. Conclusion For CLM refractory to conventional chemotherapy, combination therapy with cetuximab increases resectability rates without increasing operative mortality or liver injury. The median OS and PFS of 20 and 13 months, respectively, suggest that this novel oncosurgical strategy benefits patients with previously refractory disease who respond subsequently to cetuximab.
Actual 10-Year Survival After Resection of Colorectal Liver Metastases Defines Cure
Authors: Tomlinson James S. , Jarnagin William R. , DeMatteo Ronald P. , Fong Yuman , Kornprat Peter , Gonen Mithat , Kemeny Nancy , Brennan Murray F. , Blumgart Leslie H. , D'Angelica Michael 
Published: October 2007

Purpose Resection of colorectal liver metastases (CLM) in selected patients has evolved as the standard of care during the last 20 years. In the absence of prospective randomized clinical trials, a survival benefit has been deduced relative to historical controls based on actuarial data. There is now sufficient follow-up on a significant number of patients to address the curative intent of resecting CLM. Methods Retrospective review of a prospectively maintained database was performed on patients who underwent resection of CLM from 1985 to 1994. Postoperative deaths were excluded. Disease-specific survival (DSS) was calculated from the time of hepatectomy using the Kaplan-Meier method. Results There were 612 consecutive patients identified with 10-year follow-up. Median DSS was 44 months. There were 102 actual 10-year survivors. Ninety-nine (97%) of the 102 were disease free at last follow-up. Only one patient experienced a disease-specific death after 10 years of survival. In contrast, 34% of the 5-year survivors suffered a cancer-related death. Previously identified poor prognostic factors found among the 102 actual 10-year survivors included 7% synchronous disease, 36% disease-free interval less than 12 months, 25% bilobar metastases, 50% node-positive primary, 39% more than one metastasis, and 35% tumor size more than 5 cm. Conclusion Patients who survive 10 years appear to be cured of their disease, whereas approximately one third of actual 5-year survivors succumb to a cancer-related death. In well-selected patients, there is at least a one in six chance of cure after hepatectomy for CLM. The presence of poor prognostic factors does not preclude the possibility of long-term survival and cure.
Tumor Necrosis Factor α As a New Target for Renal Cell Carcinoma: Two Sequential Phase II Trials of Infliximab at Standard and High Dose
Authors: Harrison Michelle L. , Obermueller Eva , Maisey Nick R. , Hoare Susan , Edmonds Kim , Li Ningfeng F. , Chao David , Hall Kate , Lee Chooi , Timotheadou Eleni , Charles Kellie , Ahern Roger , King D. Mike , Eisen Tim , Corringham Robert , DeWitte Mark , Balkwill Frances , Gore Martin 
Published: October 2007

PurposeTumor necrosis factor α (TNF-α) may play a role in renal cell carcinoma (RCC). We performed two sequential phase II studies of infliximab, an anti–TNF-α monoclonal antibody, in patients with immunotherapy-resistant or refractory RCC.Patients and MethodsPatients progressing after cytokine therapy were treated with intravenous infliximab as follows: study 1 (19 patients), 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks; study 2 (18 patients), 10 mg/kg at weeks 0, 2, and 6, and then every 4 weeks. Treatment continued until disease progression (PD). Response was assessed according to Response Evaluation Criteria in Solid Tumors. Plasma levels of TNF-α, CCL2, and interleukin-6 (IL-6) were measured before and during treatment.ResultsTNF-α and its receptors were detected in malignant cells in RCC biopsies. In study 1, three patients (16%) achieved partial response (PR) and three patients (16%) achieved stable disease (SD). Median duration of response (PR + SD) was 7.7 months (range, 5.0 to 40.5+ months). In study 2, 11 patients (61%) achieved SD. Median duration of response was 6.2 months (range, 3.5 to 24+ months). One patient developed grade 3 hypersensitivity and another died as a result of pulmonary infection/sepsis. Enzyme-linked immunosorbent assay analysis of plasma revealed that higher levels of TNF-α at baseline and higher levels of CCL2 during treatment were associated with PD. There were also correlations between higher levels of TNF-α, IL-6, and CCL2 and poor survival (< 12 months).ConclusionThis is the first direct clinical evidence suggesting that TNF-α may be a therapeutic target in RCC. Plasma levels of TNF-α, IL-6, and CCL2 may have predictive and prognostic significance.
Phase II Trial of Irinotecan in Children With Refractory Solid Tumors: A Children's Oncology Group Study
Authors: Bomgaars Lisa R. , Bernstein Mark , Krailo Mark , Kadota Richard , Das Soma , Chen Zhengjia , Adamson Peter C. , Blaney Susan M. 
Published: October 2007

PurposeA phase II study was performed to determine the efficacy of irinotecan (IRN) in children with refractory solid tumors. Secondary objectives were to evaluate toxicity, pharmacokinetics, pharmacodynamics, and UGT1A1 genotype.Patients and MethodsA total of 181 patients were enrolled, of whom 171 were eligible. Patients received IRN 50 mg/m2/d for 5 days repeated every 3 weeks. Pharmacokinetic studies and UGT1A1 genotyping were performed.ResultsOf 161 patients assessable for response, one patient with hepatoblastoma had a complete response, with partial responses observed in patients with medulloblastoma (n = 4), rhabdomyosarcoma (n = 1), neuroblastoma (n = 1), and germinoma (n = 1), for an overall response rate of 5%. Grade 4 neutropenia and grade 3 to 4 diarrhea occurred in less than 7% of the courses administered. Pharmacokinetic studies were available for 79 patients. The mean ± standard deviation IRN plasma clearance was 374 ± 148 mL/min/m2, with median relative extent of conversion and relative extent of glucuronidation of 0.05 (range, 0.01 to 0.25) and 2.24 (range, 0.39 to 9.6), respectively. No association between UGT1A1 genotype (n = 61) and toxicity or pharmacokinetic parameters was observed.ConclusionIRN 50 mg/m2/d for 5 days every 21 days is well tolerated, but was not effective as a single agent in a spectrum of solid tumors, with the possible exception of patients with medulloblastoma (16% response rate). There was no association between UGT1A1*28 genotype and toxicity or pharmacokinetic parameters.
Phase I Study of Oxaliplatin, Full-Dose Gemcitabine, and Concurrent Radiation Therapy in Pancreatic Cancer
Authors: Desai Sameer P. , Ben-Josef Edgar , Normolle Daniel P. , Francis Isaac R. , Greenson Joel K. , Simeone Diane M. , Chang Alfred E. , Colletti Lisa M. , Lawrence Theodore S. , Zalupski Mark M. 
Published: October 2007

Purpose To determine a biweekly dose of oxaliplatin for combination with full-dose gemcitabine and concurrent radiation therapy (RT) in pancreatic cancer. Patients and Methods Patients with previously untreated pancreatic cancer received gemcitabine days 1, 8, and 15, and oxaliplatin days 1 and 15, repeated at 28-day intervals. RT (27 Gy in 1.8-Gy fractions) was administered during cycle 1. Dose escalation was guided using the time-to-event continuous reassessment method. Dose levels 1 to 4 included gemcitabine 1 g/m2 intravenously (IV) during 30 minutes and oxaliplatin 40, 55, 70, or 85 mg/m2 IV during 90 minutes, respectively; for dose levels 5 and 6, oxaliplatin dose remained 85 mg/m2 but infusion time for gemcitabine 1 g/m2 was increased to 65 or 100 minutes, respectively. The trial objective was to determine the dose level associated with dose-limiting toxicity (DLT) through cycle 2 in ≤ 20% of patients. Results Forty-four patients were enrolled (median age, 64 years; 27 men, 17 women) with resectable (n = 12), unresectable (n = 29), and metastatic (n = 3) pancreatic cancer. Ten DLTs occurred in nine patients, including grade 4 platelets (n = 4), decline in performance status (n = 2), GI bleeding (n = 2), and GI toxicity (n = 2). The estimated probability of DLT for dose level 3 was .21 (90% posterior probability interval [PI], .12 to .33); for dose level 4, the estimated probability was .24 (90% PI, .14 to .36). Conclusion The addition of oxaliplatin 85 mg/m2 days 1 and 15 to full-dose gemcitabine and radiation therapy was well tolerated. On the basis of these results, a multi-institutional neoadjuvant phase II study in resectable pancreatic cancer is planned.
Oligoarene Strategy for Catalyst Development. Hydroxylated Oligoarene-type Phosphines for Palladium-catalyzed Cross Coupling
Authors: Ishikawa Shunpei , Manabe Kei 
Published: October 2007

Abstract
Various oligoarene-type phosphines having a hydroxy group were synthesized based on a two-step repetitive method that we developed, and these phosphines were used as ligands for palladium in catalytic cross coupling with Grignard reagents. The study revealed that a hydroxylated terphenylphosphine accelerated the rate of the cross coupling of o-bromophenol and exhibited preference for the ortho-isomer over the meta- and para-isomers.