bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal expression of mutant and wild‐type progastrin significantly increases colon carcinogenesis in response to azoxymethane in transgenic mice
Authors: Cobb Stephanie , Wood Thomas , Ceci Jeffrey , Varro Andrea , Velasco Marco , Singh Pomila 
Published: March 2004

AbstractBACKGROUNDThe authors recently reported that transgenic mice (hGAS) expressing pharmacologic levels of progastrin (PG) (> 10 nM to 100 nM) exhibited increased susceptibility to colon carcinogenesis in response to azoxymethane (AOM). It is not known whether PG functions as a cocarcinogen at the concentrations observed in patients with hypergastrinemia (∼1.0 nM).METHODSThe authors generated transgenic mice that overexpressed either wild‐type (wtPG) or mutant (mtPG) human PG in the intestinal mucosa using the murine fatty acid binding protein (Fabp) promoter. Fabp‐PG mice and their wild‐type littermates were treated with AOM, and their colons were examined for preneoplastic (aberrant crypt foci [ACF]) and neoplastic (adenomas [Ads] and adenocarcinomas [AdCas]) lesions after 2 weeks and 6 months of treatment.RESULTSACF and tumors were significantly more common (by a factor of ∼2) in colon specimens from both Fabp‐wtPG mice and Fabp‐mtPG mice relative to wild‐type mice. It is noteworthy that the multiplicity of ACF and the total number of small and large Ads and AdCas were significantly greater in colon specimens from Fabp‐PG mice compared with colon specimens from wild‐type mice, irrespective of gender.CONCLUSIONSThe results of the current study suggest that at concentrations (∼1.0 nM) far lower than the ones observed in hGAS mice, PG functions as an equally potent cocarcinogen and significantly increases the risk of colon carcinogenesis in response to AOM. Thus, PG may represent a clinically relevant target molecule in patients with hypergastrinemia or colon carcinoma. Cancer 2004. © 2004 American Cancer Society.
Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis
Authors: Hao Xishan , Sun Baocun , Hu Limei , Lähdesmäki Harri , Dunmire Valerie , Feng Yumei , Zhang Shi‐Wu , Wang Huamin , Wu Chunlei , Wang Hua , Fuller Gregory N. , Symmans W. Fraser , Shmulevich Ilya , Zhang Wei 
Published: March 2004

AbstractBACKGROUNDMetastatic disease is a major adverse prognostic factor in breast carcinoma. Lymph node metastases often represent the first step in the metastatic process.METHODSTo gain insight into the molecular events that underlie breast carcinoma metastasis, the authors compared gene expression profiles, obtained by cDNA microarray analysis, of nine matched primary tumors and metastases after screening for enrichment of tumor cells. Statistical analysis identified genes that are expressed at elevated or decreased levels in metastases relative to the corresponding primary tumors. Multidimensional scaling analysis indicated that in terms of expression levels, primary tumors were tightly clustered, whereas metastases exhibited a greater spread; this finding points to the more heterogeneous nature of metastases. Among the differentially expressed entities were the invasion‐ and tissue modeling–related genes IGFBP5, fibronectin, and MMP2; the cell cycle regulatory gene cyclin D1; other genes, such as enolase 2; and an expressed sequence tag similar to angiopoietin 1. To validate and extend these initial findings, the authors constructed a tissue microarray consisting of 100 primary malignancies paired with their lymph node metastases. Antibodies for the IGFBP‐5, fibronectin, MMP‐2, cyclin D1, and MDM‐2 proteins were used to stain tissue array sections.RESULTSConsistent with microarray data, statistically significant overexpression of IGFBP‐5, down‐regulation of cyclin D1, and unchanged MDM‐2 levels were observed in metastatic tumor cells. Nonetheless, although fibronectin and MMP2 mRNA expression levels were decreased in many metastasis specimens, expression levels of the corresponding proteins in the extracellular matrix were elevated in most metastases. Decreased expression of fibronectin and MMP2 in lymph node metastases was further confirmed by real‐time polymerase chain reaction assays performed on five additional specimen pairs.CONCLUSIONSThe results of the current study suggest that extracellular matrix protein expression and nuclear gene expression are associated via a negative‐feedback regulatory mechanism. Therefore, gene expression profiling and tissue array validation should be combined to elucidate molecular events associated with the metastatic process. Cancer 2004. © 2004 American Cancer Society.
Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumors
Authors: Tzika A. Aria , Astrakas Loukas G. , Zarifi Maria K. , Zurakowski David , Poussaint Tina Young , Goumnerova Liliana , Tarbell Nancy J. , Black Peter McL. 
Published: March 2004

AbstractBACKGROUNDIn vivo biomarkers to predict progression of brain tumors are of great value in clinical practice. Therefore, the authors tested the hypothesis that changes in choline ratios by magnetic resonance (MR) spectroscopic imaging and/or relative tumor blood volume (rTBV) can differentiate clinically stable from progressive pediatric brain tumors.METHODSMR spectroscopic imaging examinations were performed on 27 children with neuroglial brain tumors during therapy on a 1.5‐Tesla MR system. Normalized rTBV values were measured in 11 of 27 patients. Each examination was rated as stable or progressive by clinical and imaging criteria.RESULTSThe percent change in normalized choline (Cho) was significantly greater in patients who had progressive examinations compared with patients who had stable examinations (P = 0.03). The percent change in Cho/N‐acetylaspartate (Cho/NAA) was significantly higher in patients who had progressive outcomes (n = 18 patients) compared with patients who had stable outcomes (n = 32 patients; P < 0.001; sensitivity, 0.89; specificity, 0.88) and was identified as the most important prognostic indicator of tumor progression by logistic regression (likelihood ratio test, 33.4; P < 0.001). The odds of tumor progression were approximately 55 times greater for patients who showed at least a 20% change in Cho/NAA. rTBV distinguished between progressing and stable tumors (P = 0.03), and Cho/NAA and rTBV values showed interaction to predict the probability of a progressing clinical outcome.CONCLUSIONSThe percent change in Cho/NAA by proton MR spectroscopic imaging, assisted by rTBV, was useful in predicting tumor progression in children with brain tumors. Cancer 2004. © 2004 American Cancer Society.
Expression of regenerating gene I in gastric adenocarcinomas
Authors: Dhar Dipok Kumar , Udagawa Jun , Ishihara Shunji , Otani Hiroki , Kinoshita Yoshikazu , Takasawa Shin , Okamoto Hiroshi , Kubota Hirofumi , Fujii Toshiyuki , Tachibana Mitsuo , Nagasue Naofumi 
Published: March 2004

AbstractBACKGROUNDRegenerating gene I (REG) was identified as a growth factor for pancreatic islet beta cells. Enhanced REG expression was observed during the healing of gastric mucosa. REG expression was observed in various tumors including gastric carcinoma, but to the authors' knowledge, the correlation between REG expression and clinicopathologic characteristics and patient prognosis have not been evaluated.METHODSThe REG messenger RNA level was analyzed by Northern blot analysis and localization was performed by in situ hybridization and immunohistochemistry in gastric adenocarcinoma specimens. The correlations between REG expression and clinicopathologic features and survival of the patients were analyzed.RESULTSOf the 68 patients studied, 24 (35%) were positive for REG. There was a significant consistency in the intensity and localization of REG transcript and protein expressions. REG expression was enhanced in advanced T classification tumors and in tumors that were not well differentiated. A significant number of metastatic lymph nodes were present in REG‐positive tumors. Overall and disease‐free survival were found to be poor for patients with REG‐positive tumors. REG expression was reported to be an independent predictor of overall patient survival.CONCLUSIONSDetermination of REG expression may help to identify aggressive gastric tumors and to tailor appropriate therapy for patients with REG‐positive tumors. Cancer 2004. © 2004 American Cancer Society.
Restaging surgery for women with borderline ovarian tumors
Authors: Fauvet Raffaèle , Boccara Joëlle , Dufournet Charlotte , David‐Montefiore Emmanuel , Poncelet Christophe , Daraï Emile 
Published: March 2004

AbstractBACKGROUNDThe purpose of the current study was to examine the surgical management of women with borderline ovarian tumors and the adequacy of initial staging according to the guidelines of the International Federation of Gynecology and Obstetrics; to evaluate the impact of restaging operations; and to identify risk factors for initial understaging.METHODSIn a retrospective French multicenter study, 54 of 360 women with borderline ovarian tumors underwent a restaging operation. After excluding women with initial complete staging (n = 62), epidemiologic, surgical, and histologic parameters and risk of recurrence were compared between women who underwent restaging (n = 54) and those who did not (n = 244).RESULTSOne hundred fifty (41.6%) of 360 women underwent intraoperative histologic examination, which led to the diagnosis of a borderline tumor in 97 cases (64.7%). Thirty‐seven (38.1%) of these 97 women had undergone complete initial staging procedures. A restaging operation was performed for 54 women. A lower median age and a higher rate of conservative treatment were noted in the group that underwent restaging. Eight (14.8%) of the 54 women who underwent restaging had their tumors upstaged: 7 of the 41 cases initially diagnosed as Stage IA tumors were upstaged to Stage IB (n = 3) or to Stage IIA, IIB, IIIA, or IIIC (n = 1 for each); in the eighth case, a Stage IC tumor was upstaged to Stage IIIA. Upstaging tended to be more common in women with serous borderline tumors (P = 0.06) and in women who underwent cystectomy (P = 0.08). There was no difference in recurrence rates according to whether a restaging operation was performed. The recurrence rates after conservative and radical treatment were 15.6% (25 of 160) and 4.5% (9 of 200), respectively (P < 0.001).CONCLUSIONSWomen who initially were diagnosed with Stage IA disease and who had serous borderline tumors or underwent cystectomy appeared to derive the most benefit from restaging surgery. Nonetheless, the indications for restaging surgery remain controversial, as no difference in recurrence rate was observed between women who underwent restaging and those who did not. Cancer 2004. © 2004 American Cancer Society.
Comparison of plasma Epstein–Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma
Authors: Shao Jian‐Yong , Li Yu‐Hong , Gao Hong‐Yi , Wu Qiu‐Liang , Cui Nian‐Ji , Zhang Li , Cheng Gang , Hu Li‐Fu , Ernberg Ingemar , Zeng Yi‐Xin 
Published: March 2004

AbstractBACKGROUNDSerologic measurement of antibodies to Epstein–Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group.METHODSReal‐time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme‐linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non‐NPC tumors, and in 47 control individuals.RESULTSThe median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non‐NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers ≥ 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers ≤ 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC.CONCLUSIONSThe results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor. Cancer 2004. © 2004 American Cancer Society.
Gemcitabine and docetaxel as front‐line chemotherapy in patients with carcinoma of an unknown primary site
Authors: Pouessel Damien , Culine Stéphane , Becht Catherine , Ychou Marc , Romieu Gilles , Fabbro Michel , Cupissol Didier , Pinguet Frédéric 
Published: March 2004

AbstractBACKGROUNDThe current study was performed to evaluate the efficacy and toxicity of a noncisplatin‐based chemotherapy regimen combining gemcitabine and docetaxel as front‐line chemotherapy for patients with carcinoma of an unknown primary site.METHODSPatients were to receive intravenous gemcitabine at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 and docetaxel at a dose of 75 mg/m2 over 1 hour on Day 8 in an outpatient setting. The schedule was repeated every 3 weeks for a maximum of 6 cycles.RESULTSThirty‐five patients were assessable for response and survival. One complete and 13 partial responses were observed. The overall response rate was 40% (95% confidence interval, 28–52%). The median time to disease progression was 2 months (range, 1–4 months). The median overall survival time was 10 months (range, 0–32 months). Toxicity was reported to be manageable.CONCLUSIONSThe combination of gemcitabine and docetaxel was found to be active in patients with carcinomas of an unknown primary site. However, the overall outcome of these patients remains poor and novel treatment approaches are required. Cancer 2004. © 2004 American Cancer Society.
Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: Who benefits?
Authors: Zang Rong‐Yu , Li Zi‐Ting , Tang Jie , Cheng Xi , Cai Shu‐Mo , Zhang Zhi‐Yi , Teng Nelson N. 
Published: March 2004

AbstractBACKGROUNDThis study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression‐free interval ⩾ 3 months.METHODSOne hundred seventeen patients with relapsed EOC after a clinical complete remission duration ≥ 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan–Meier method, and statistical comparisons were performed using log‐rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model.RESULTSThe median patient age at the time of relapse was 53 years (range, 20–78 years). The median survival was 22 months and the estimated 5‐year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to ≥ 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured ≤ 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. ≤ 1 cm [P = 0.1211], ≤ 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1–2 cycles vs. 3–5 cycles [P = 0.0144]; 1–2 cycles vs. ≥ 6 cycles [P < 0.0001]; and 3–5 cycles vs. ≥ 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106).CONCLUSIONSSCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted ≥ 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy. Cancer 2004. © 2004 American Cancer Society.
Genetic alterations in early‐stage pulmonary large cell neuroendocrine carcinoma
Authors: Hiroshima Kenzo , Iyoda Akira , Shibuya Kiyoshi , Haga Yukiko , Toyozaki Tetsuya , Iizasa Toshihiko , Nakayama Toshinori , Fujisawa Takehiko , Ohwada Hidemi 
Published: March 2004

AbstractBACKGROUNDSmall cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are high‐grade malignant neuroendocrine tumors. Histologic differentiation between SCLC and LCNEC is difficult in some cases and to the authors' knowledge, genetic alterations associated with LCNEC have not been identified. Therefore, the authors studied genetic alterations found in LCNEC and compared them with those of SCLC and classic large cell carcinoma (CLCC).METHODSTwenty‐two patients with UICC TNM Stage I LCNEC, 12 patients with Stage I CLCC, and 11 patients with SCLC with limited disease were studied. All tumors were resected completely. Loss of heterozygosity (LOH) of the tumor cells was detected using fluorescent primers. Methylation status of the p16 gene and expression of the p53 protein, retinoblastoma protein, and p16 protein were evaluated immunohistochemically.RESULTSLOH at TP53 and 13q14 was observed in most patients. The prevalence of LOH at D3S1295, D3S1234, and D5S407 was significantly higher in patients with LCNEC and SCLC than in patients with CLCC. The prevalence of LOH at D5S422 was higher in patients with CLCC and in patients with SCLC than in patients with LCNEC. Expression of the p16 protein was observed more frequently in SCLC than in CLCC or LCNEC. Hypermethylation of the p16 gene was observed more frequently in LCNEC than in SCLC. Patients with allelic losses at D3S1234 and D10S1686 had poorer prognoses compared with patients without allelic losses at these sites.CONCLUSIONSGenetic alterations of LCNEC were akin to those of SCLC. However, allelic losses at 5q and abnormalities in the p16 gene may differentiate LCNEC from SCLC. Cancer 2004. © 2004 American Cancer Society.
A randomized clinical trial of energy conservation for patients with cancer‐related fatigue
Authors: Barsevick Andrea M. , Dudley William , Beck Susan , Sweeney Carole , Whitmer Kyra , Nail Lillian 
Published: March 2004

AbstractBACKGROUNDThe efficacy of energy conservation and activity management (ECAM) for fatigue reduction and maintenance of functional performance has never been evaluated in adults with cancer who are undergoing treatment.METHODSA randomized clinical trial compared an ECAM intervention with a control intervention focused on nutrition. Individuals initiating chemotherapy, radiotherapy, or concurrent therapy for cancer were randomized to receive either the semistructured ECAM intervention (n= 200) or the control intervention (n= 196). Participants in each group participated in 3 telephone sessions with an oncology nurse during the first 5 weeks of treatment. Data on fatigue and limitation of functioning were obtained before cancer treatment and at two follow‐up points that coincided with times of high fatigue for each type of treatment. The outcomes of interest included perception of fatigue and functional performance.RESULTSA repeated‐measures analysis of covariance using the type of cancer treatment as a covariate revealed a significant study group–by‐time interaction indicating that the ECAM group experienced a greater decrease in fatigue over time compared with the control group (F2,544= 4.5;P= 0.01). The intervention was not associated with changes in overall functional performance.CONCLUSIONSIndividuals who received the ECAM intervention derived a modest but significant benefit from it. To achieve a more robust clinical benefit from the intervention, it may be necessary to manage other key symptoms in addition to fatigue. Research is needed to examine symptom clusters or combinations associated with negative outcomes as well as combination strategies for symptom management. Cancer 2004. © 2004 American Cancer Society.
Neutral and Cationic Methylaluminium Complexes of 2‐Anilinotropone Ligands: Synthesis, Characterization, and Reactivity toward Ethylene
Authors: Pappalardo Daniela , Mazzeo Mina , Montefusco Pasquale , Tedesco Consiglia , Pellecchia Claudio 
Published: March 2004

AbstractSome new aluminium complexes bearing bidentate monoanionic 2‐anilinotroponate ligands have been synthesized and characterized. Reaction of 2‐(2,6‐diisopropylanilino)tropone or 2‐(perfluoroanilino)tropone with AlMe3 (1 equiv.) gave, by methane elimination, compounds [2‐(2,6‐diisopropylanilino)tropone]AlMe2 (1) and [2‐(perfluoroanilino)tropone]AlMe2 (2), respectively, as yellow solids. Reaction of 1 with 1 equiv. of the ligand furnished, by protodealumination of a second Al−CH3 bond, the [2‐(2,6‐diisopropylanilino)tropone]2AlMe derivative 3. The structure of 3 has been determined by single‐crystal X‐ray diffraction, showing a five‐coordinate aluminium atom with a distorted trigonal‐bipyramidal geometry. Compounds 1 and 3 underwent methyl abstraction reactions with B(C6F5)3; the resulting cationic species was trapped in the presence of THF in dichloromethane solution. The reactivity of the synthesized compounds in ethylene polymerisation has also been explored. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)