bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gauging the impact of breast carcinoma screening in terms of tumor size and death rate
Authors: Michaelson James S. , Satija Sameer , Kopans Daniel , Moore Richard , Silverstein Melvin , Comegno Arthur , Hughes Kevin , Taghian Alphonse , Powell Simon , Smith Barbara 
Published: October 2003

AbstractBACKGROUNDWhile the question of whether the trials of breast cancer screening have resulted in a reduction in breast cancer death has been the subject of much scrutiny, there has been less attention to the reduction in tumor size achieved by screening.METHODSSize data for invasive breast tumors were assembled from a variety of sources. The health consequences that can be expected from finding tumors of various sizes were determined using a recently developed mathematical method for relating tumor size to death rate.RESULTSFirst, in both the Swedish two‐country trial and at the MGH Breast Imaging Division, the sizes of the invasive breast cancers in the screening population (those masses seen at screening together with those found as palpable masses after screening examinations) were sufficiently smaller than the cancers found among women who had not used screening to have lead to considerable reductions in death. Second, the lack of reduction in death rates detected in both Canadian National Breast Screening Studies could be ascribed to the small reductions in tumor size achieved in these studies. Third, radiographic density had a small effect, whereas age had a negligible effect, on the capacity of mammographic screening to find breast carcinomas at smaller, and thus less lethal, sizes.CONCLUSIONSPrompt attendance at annual mammographic screening offers the potential to reduce tumor size and, presumably, breast carcinoma death, in women of all ages and density groups. Cancer 2003. © 2003 American Cancer Society.
Prognosis after regional lymph node recurrence in patients with Stage I–II breast carcinoma treated with breast conservation therapy
Authors: Harris Eleanor E. R. , Hwang Wei‐Ting , Seyednejad Farshad , Solin Lawrence J. 
Published: October 2003

AbstractBACKGROUNDThe authors evaluated the risk factors for regional lymph node recurrence and the prognosis of patients with regional nodal recurrence after breast conservation therapy for Stage I–II breast carcinoma.METHODSBetween 1977 and 1995, 1293 women with pathologic Stage I and II (T1–2, N0–1) breast carcinoma were treated with breast‐conserving therapy including lumpectomy, axillary lymph node dissection, and definitive breast irradiation. A total of 39 women (3%) had any regional lymph node recurrence. The median follow‐up was 8.5 years (range, 1.5–24 years).RESULTSAmong 39 patients with a regional lymph node recurrence, 10 women had regional recurrence only, 16 had simultaneous locoregional recurrence, and 13 had simultaneous regional and distant recurrence. Regional recurrence occurred in the axillary lymph nodes only (n= 21; 51%), supraclavicular lymph nodes only (n= 8; 23%), internal mammary lymph nodes only (n= 3; 8%), infraclavicular lymph nodes only (n= 3; 8%), or multiple lymph node sites (n= 4; 10%). The median time to regional lymph node recurrence was 3.1 years (range, 0.2–20.9 years). Overall survival after regional‐only disease recurrence was 44%, locoregional disease recurrence was 26%, and regional with distant disease recurrence was 12%. Cause‐specific survival rates at 10 years for the 3 groups were 44%, 40%, and 12%, respectively. For patients who presented with simultaneous regional and distant metastases, the median survival period was 1.1 years, compared with 5.2 years for women who developed distant disease subsequent to regional recurrence.CONCLUSIONSRegional lymph node recurrence after breast conservation therapy may be salvaged, but is associated with a high rate of either simultaneous or subsequent distant metastatic dissemination and poor overall prognosis. Cancer 2003. © 2003 American Cancer Society.
Mismatch repair gene expression defects contribute to microsatellite instability in ovarian carcinoma
Authors: Geisler John P. , Goodheart Michael J. , Sood Anil K. , Holmes Richard J. , Hatterman‐Zogg Melanie A. , Buller Richard E. 
Published: October 2003

AbstractBACKGROUNDhMLH1, the human MutL homologue, has been linked to microsatellite instability (MSI) in gastrointestinal tumors. However, to the authors' knowledge, the role of hMLH1, the other mismatch repair genes (MMR), and MSI in ovarian carcinoma has not been well defined. The purpose of the current study was to determine the relation between MSI of ovarian carcinoma and MMR gene expression, hMLH1 and hMSH2 hypermethylation, and hMLH1 and hMSH2 null mutations.METHODShMLH1 mRNA was detected by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and amplification of cDNA using a housekeeping gene (glycerol 3‐phosphate dehydrogenase) as a control for mRNA quality and quantity. Methylation‐specific PCR (MS‐PCR) was used to correlate methylation of the hMLH1 and hMSH2 CpG islands with mRNA expression status. Similar techniques were used to evaluate the concomitant expression of five other MMR: hMSH2, hMSH3, hMSH6, PMS1, and PMS2. Microsatellite instability was studied using the National Cancer Institute consensus markers (D2S123, D5S346, D17S250, BAT25, and BAT26) and NM23 as described previously.RESULTSOne hundred twenty‐five primary tumors were analyzed. High‐frequency MSI (MSI‐H) was found in 21 tumors (16.8%). hMLH1 mRNA was absent in 10 of these 21 tumors (47.6%). In each case, coordinated hypermethylation of both regions A and C of the promoter was identified. Microsatellite stable and low‐frequency MSI tumors all were found to express not only hMLH1 but the other MMR genes as well (P < 0.001). Absence of expression of hMSH2 and the four other MMRs occurred in tumors with absent hMLH1 mRNA expression because of CpG island hypermethylation. No absence of expression of hMSH2, hMSH3, hMSH6, PMS1, or PMS2 was found to occur in tumors expressing hMLH1. None of the 11 MSI‐H tumors without promoter hypermethylation demonstrated a null mutation in hMLH1 or hMSH2.CONCLUSIONSA molecular mechanism to explain > 50% of the MSI‐H phenotype in ovarian carcinoma cases was demonstrated. MSI‐H may occur because of MMR defects, especially hMLH1 promoter hypermethylation. Additional mechanisms are required to explain the balance between the cases of MSI‐H as well as the phenomenon of MSI‐L tumors. Cancer 2003. © 2003 American Cancer Society.
Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon 388 is associated with prognosis in high‐grade soft tissue sarcoma
Authors: Morimoto Yuki , Ozaki Toshifumi , Ouchida Mamoru , Umehara Norifumi , Ohata Norihide , Yoshida Aki , Shimizu Kenji , Inoue Hajime 
Published: October 2003

AbstractBACKGROUNDA recent study revealed that single nucleotide polymorphism (SNP) at codon 388 (Gly or Arg) of fibroblast growth factor receptor 4 (FGFR4) was associated with prognosis in patients with carcinoma of the breast and colorectal carcinoma. The purpose of the current study was to investigate the correlation between codon 388 SNP and clinical prognosis in patients with sarcoma of the bone and soft tissues.METHODSTumor samples were obtained from 143 patients with high‐grade bone and soft tissue sarcomas at Okayama University Hospital between 1986–2002, and from 102 healthy volunteers. SNP of codon 388 was detected by sequencing and fragment length of polymerase chain reaction products digested by restriction enzyme. The chi‐square test was used to compare genotype distribution and the Kaplan–Meier method was used for survival analysis.RESULTSWith regard to FGFR4 genotypes in the 143 patients studied, 54 (37.8%) were Gly/Gly, 72 (50.3%) were Gly/Arg, and 17 (11.9%) were Arg/Arg, findings that were not significantly different from those of controls (P = 0.97). With regard to cumulative overall and metastasis‐free survival, patients with the Gly/Gly genotype were found to have a better prognosis (P = 0.085 and P = 0.27, respectively). FGFR4 SNP was found to be correlated significantly with overall and metastasis‐free survival in patients with soft tissue sarcomas (P = 0.029 and P = 0.045, respectively), but not in those patients with bone sarcomas (P = 0.88 and P = 0.75, respectively).CONCLUSIONSIn the current study, the authors found a significant correlation between FGFR4 SNP and prognosis in patients with soft tissue sarcoma, although the samples were comprised of various histologic types. This SNP might be used to improve the prediction of clinical prognosis and lead to new treatment strategies in patients with soft tissue sarcomas. Cancer 2003. © 2003 American Cancer Society.
Decreased abundance of trefoil factor 1 transcript in the majority of gastric carcinomas
Authors: Beckler Andrew D. , Roche James K. , Harper Jeffrey C. , Petroni Gina , Frierson Henry F. , Moskaluk Christopher A. , El‐Rifai Wa'el , Powell Steven M. 
Published: October 2003

AbstractBACKGROUNDGastric carcinoma is one of the leading causes of cancer‐related death worldwide, but the mechanisms underlying its development and progression still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1) expression leads to neoplastic growth in the antropyloric mucosa of mice, the authors sought to comprehensively study the human TFF1 gene in primary gastric carcinomas.METHODSThe authors studied the human TFF1 gene in primary gastric carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through DNA sequencing, quantitative real‐time reverse transcriptase‐polymerase chain reaction, and immunohistochemistry.RESULTSStrikingly, TFF1 mRNA expression was significantly decreased in all 37 gastric carcinomas studied compared with normal gastric mucosa. Furthermore, six tumor/normal pairs with available histologic samples demonstrated a marked decrease in protein expression in tumor samples. Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors did not reveal any somatic mutations, although a few rare germline sequence variants were identified.CONCLUSIONSThese findings demonstrated a significant decrease in the TFF1 transcript in the majority of human gastric carcinomas along with a corresponding reduction in protein expression, both of which occurred in the absence of gene mutation. Dysregulation of TFF1 expression at the transcript level was a critical event in the development of most gastric carcinomas. Cancer 2003. © 2003 American Cancer Society.
10q25.3 (DMBT1) copy number changes in astrocytoma grades II and IV
Authors: Wessels Peter H. , Twijnstra Albert , Kubat Bela , Ummelen Monique I.J. , Claessen Sandra M.H. , Sciot Raf , Merlo Adrian , Ramaekers Frans C.S. , Speel Ernst J.M. , Hopman Anton H.N. 
Published: October 2003

AbstractIn the literature, it has been suggested that loss of the 10q25‐26 region, including the DMBT1 gene (10q25.3), is correlated with initiation and/or malignant progression of astrocytomas, although the results of the studies on the loss of heterozygosity that led to this assumption are not unequivocal. For this reason, using double‐target fluorescence in situ hybridization, we compared copy number changes of 10q25.3 to those of the pericentromeric region (10q12) in 10 cases each of astrocytoma grades II and IV. The same specimens were analyzed for copy number changes of chromosome 1, as a marker for polyploidy, and chromosome 7, which is often gained in astrocytomas of all grades. Our results show that selective loss of the 10q25.3 region was present in 2 of 10 specimens in both astrocytoma grade II and grade IV, occurring only in tumors with polysomy for 10q12. Furthermore, astrocytoma grade II often showed polyploidy for chromosomes 1, 7, and 10 (8 of 10 specimens). In addition, astrocytoma grade IV frequently exhibited losses of chromosome 10 in a high percentage of nuclei. Although based on a small number of cases, the results clearly show that loss of the 10q25.3 region is uncommon in astrocytoma grade II and mostly coincident with loss of chromosome 10 in grade IV tumors. These data indicate that selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II. © 2003 Wiley‐Liss, Inc.
Two variants of the human hepatocellular carcinoma‐associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B
Authors: Wan Dafang , He Mei , Wang Junru , Qiu Xiaokun , Zhou Wei , Luo Zewei , Chen Jianguo , Gu Jianren 
Published: October 2003

AbstractWe have cloned a cDNA from chromosome band 17p13.3, designated as HCAP1 (HCC‐associated protein 1, originally named HC56). Database searches revealed that HCAP1 shares most of its open reading frame with GEMIN4. Single nucleotide polymorphism (SNP) screening revealed a high incidence of SNP in the coding region of HCAP1 (12 SNP sites). A collection of 140 controls and 22 cases from the Qidong area was genotyped at 6 SNP sites. The 22 cases exhibited higher frequencies of minor alleles than did the controls, and 2 sites revealed significant differences between the controls and the cases. We constructed 2 haplotypes, HCAP1‐N (with common alleles at 5 SNP sites) and HCAP1‐M (with minor alleles at 5 SNP sites), in a mammalian expression system. Both haplotypes resulted in a remarkable reduction in colony formation and suppression of cell growth after being transfected into the human hepatocellular carcinoma (HCC) cell line. The inhibitory effect of HCAP1‐N was stronger than that of HCAP1‐M. Different haplotypes also resulted in different gene expression profiles in the Hep3B cell line according to an examination of 588 genes on an Atlas membrane. The expression induced by HCAP1‐M caused an up‐regulation of genes involved in cellular proliferation and a down‐regulation of genes involved in cellular apoptosis and DNA repair. These results, in addition to the statistical data, are biological evidence that the HCAP1‐M variant of HCAP1 has a reduced inhibitory effect on hepatocarcinoma cell growth and an impaired DNA repair system. This suggests that HCAP1‐M may be related to cancer susceptibility. © 2003 Wiley‐Liss, Inc.
Estimating the marginal value of ‘better’ research output: ‘designed’ versus ‘routine’ data in randomised controlled trials
Authors: Cohen David , Longo Mirella F , Williams John , Cheung Wai‐yee , Hutchings Hayley , Russell I.T. 
Published: October 2003

AbstractWe recently completed a study which demonstrated that the costs of health technology assessment (HTA) by randomised controlled trial (RCT) can be reduced by substituting routine datasets for data designed and collected specifically for a trial. This cost reduction, however, had the effect of reducing the quality of the research output. In the present study we attempted to tease out the values attached to the ‘better’ information provided by designed data RCTs using a mock grants committee. Two valuation techniques, implied values and willingness to pay, were used. Ex ante valuations were determined by comparing alternative research proposals – a more costly version using designed data and a cheaper version using routine data. Ex post valuations were determined by comparing results of both versions. The exercise was performed on four exemplar studies. Overall, the committee expressed a general lack of trust towards routine data both ex ante and ex post and placed high values on the better information from the designed data studies – particularly information on preferences. This suggests that currently available routine datasets are not perceived to be able to provide efficient alternatives to designed data for RCTs. Copyright © 2003 John Wiley & Sons, Ltd.
Metachronous spread of parathyroid carcinoma to a retropharyngeal lymph node
Authors: Rufener Justin B. , Cohen James I. 
Published: October 2003

AbstractBackground.Parathyroid carcinoma is rare and accounts for approximately 1% of patients with hyperparathyroidism. It is a slowly progressive disease with frequent recurrence and high incidence of local metastasis. Because of the rarity of this tumor, little is known about the pattern of lymph node metastasis.Methods.A case of retropharyngeal lymph node metastasis found 2 years after initial diagnosis of parathyroid carcinoma is presented and discussed.Results.A 67‐year‐old man initially was seen with asymptomatic hypercalcemia, and a 1.7‐cm mass was removed along with the left hemithyroid. The mass was found to be parathyroid carcinoma. Serum calcium was again elevated 1 year later, and left neck lymph node dissection revealed an upper jugular lymph node containing parathyroid carcinoma. The patient continued to have an elevated serum calcium level, and a retropharyngeal lymph node was found by MRI and removed the following year. The patient is now without evidence of hyperparathyroidism or recurrent disease at 2‐year follow‐up.Conclusions.Persistent parathyroid carcinoma is often a clinical challenge because of the difficulty in localizing recurrent tumor. Retropharyngeal lymph nodes should be considered as a possible site of metastasis in patients with parathyroid carcinoma. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Basaloid in contrast to nonbasaloid head and neck squamous cell carcinomas display aberrations especially in cell cycle control genes
Authors: Poetsch Micaela , Lorenz Gerd , Bankau Alexander , Kleist Britta 
Published: October 2003

AbstractBackground.At present, the differences between head and neck basaloid squamous cell carcinoma (BSCC) and nonbasaloid squamous cell carcinoma (SCC) are mostly on the basis of histologic and immunohistologic findings.Methods.In this study, we investigated 8 BSCCs and 59 SCCs for loss of heterozygosity (LOH) at chromosomes 5q, 9p, 9q, 10q, 11q, 13p, 17p, and 18q. In addition, we analyzed p16, PTEN, and CCND1 (cyclin D1) and investigated the HPV status. Immunohistochemically, the expression of MIB‐1, p16, p53, and cyclin D1 was determined.Results.Aberrations in the BSCCs were especially frequent at 9p and in the CCND1 gene. In contrast, alterations at 10q occurred almost exclusively in conventional SCCs. Obvious differences could be determined concerning the HPV status: HPV‐DNA was detected in all BSCCs but only in 17% of conventional SCCs.Conclusions.Although the number of investigated BSCCs is rather low and did not allow statistical conclusions, our results focus on certain differences between the molecular pathogenesis of BSCCs and SCCs. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Management of neurotropic low‐grade B‐cell lymphoma: Report of two cases
Authors: Garcia‐Serra Allie , Price Mendenhall Nancy , Hinerman Russell W. , Lynch James W. , Braylan Raul C. , Mancuso Anthony A. 
Published: October 2003

AbstractBackground.Low‐grade lymphomas do not commonly involve the central or peripheral nervous system.Methods.Case report and review of the literature of two cases of B‐cell lymphoma of the extranodal marginal zone type involving the head and neck region with evidence of extensive neurotropism are detailed in this report.Results.One patient was initially seen with a mass in the temporalis muscle and the other with a masticator space mass. The clinical course was indolent in both cases, although associated imaging studies suggested a more aggressive tumor. Both patients were treated with moderate‐dose radiotherapy only. At the time of writing, one patient has no evidence of disease 6.5 years after treatment and the other at 6 months.Conclusions.This suggests that some marginal zone lymphomas exhibit a low‐grade clinical course despite an aggressive radiographic pattern of perineural and neurotropic spread. This type of lymphoma might be effectively treated with moderate‐dose radiotherapy. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Neck level–specific nodal metastases in oropharyngeal cancer: Is there a role for selective neck dissection after definitive radiation therapy?
Authors: Doweck Ilana , Robbins K. Thomas , Mendenhall William M. , Hinerman Russell W. , Morris Christopher , Amdur Robert 
Published: October 2003

AbstractPurpose.To determine the extent of the required neck dissection for patients with persistent lymphadenopathy after definitive radiation therapy for oropharyngeal cancer. If feasible, a conservative approach using selective neck dissection would likely minimize the extent of neck fibrosis and other adverse sequelae.Methods.Analysis of pretreatment and posttreatment radiologic scans and pathology reports of 76 patients with oropharyngeal carcinoma (35 tonsil; 41 base of tongue), who had radiologic evidence of persistent nodal disease for level‐specific involvement. Patients were treated with twice‐daily fractionations of external‐beam radiation therapy (median dose, 76.8 Gy to the primary tumor) and planned neck dissection (levels I–V) for bulky nodes (N2–3) or salvage neck dissection for N1 disease.Results.The distribution of clinical nodal disease by neck level on the basis of pretreatment and posttreatment radiologic scans indicated levels II and III to be most commonly involved. The false‐negative rate for the restaging radiologic scans for each neck level was as follows: level I, 0%; level II, 8%; level III, 6%; level IV, 5%; and level V, 1.5%. Of the eight hemi‐necks found to contain positive pathologic nodes in a neck level judged to be negative on the basis of restaging scans, five of the patients subsequently had disease recurrence in the primary site. Patients who had evidence of residual neck disease had a significantly lower rate of locoregional control (77% vs 100%, p = .0005).Conclusions.The extent of neck dissection for patients with nodal disease associated with oropharyngeal cancer treated with radiation therapy should include levels II–IV. It is reasonable to spare levels I and V in patients without radiologic and clinical evidence of positive nodes in levels I and V. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000–000, 2003
Long‐term control of food intake and body weight by hydrodynamics‐based delivery of plasmid DNA encoding leptin or CNTF
Authors: Jiang Jingjing , Yamato Eiji , Miyazaki Jun‐ichi 
Published: October 2003

AbstractBackgroundObesity contributes to many common diseases, including cardiovascular and metabolic disorders such as diabetes, hypertension, and stroke. Leptin and ciliary neurotrophic factor (CNTF), two members of the cytokine family, play important roles in controlling food intake and body weight in rodents. Here, we used the hydrodynamics‐based gene delivery technique to introduce leptin and CNTF expression plasmids, pCAGGS‐leptin and pCAGGS‐CNTF, into mice and to assess whether they could induce high expression of leptin or CNTF and reduce food intake and body weight in the mice.MethodsPlasmid DNA (50 µg) in lactated Ringer's solution (0.1 ml/g body weight) was rapidly injected into the tail vein of 4‐week‐old male MCH‐ICR mice.ResultsAfter a single injection, serum leptin peaked (at 32.0 ± 3.1 ng/ml) 2 days after the injection, and serum CNTF peaked (at 22.0 ± 0.8 µg/ml) 1 day after the injection. The high expression of either leptin or CNTF was sustained and dramatically reduced food intake (CNTF and leptin group vs. control group; 2.3 ± 0.5 and 3.1 ± 0.5 g/day vs. 4.8 ± 0.6 g/day; p < 0.001) and body weight (3 weeks after the injection; CNTF and leptin group vs. control group; −19.5% and +3.3% vs. +33.3–47.5%; p < 0.001) in the mice, suggesting potent in vivo activities for these exogenously expressed proteins.ConclusionsThese results suggest that hydrodynamics‐based gene delivery could have broad applications in the study of appetite regulation and metabolism. Copyright © 2003 John Wiley & Sons, Ltd.