bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Critical Basic Residue on the Ecotropic Murine Leukemia Virus Receptor
Authors: Qian Zhaohui , Donald Robin , Wang Hongzhe , Chen Qianmin , Albritton Lorraine M. 
Published: July 2003

ABSTRACT
Susceptibility to ecotropic murine leukemia viruses (MLV) is restricted to mice and rats at the level of virus binding to the host cell receptor. Asparagine 232, valine 233, tyrosine 235, and glutamic acid 237 in the third extracellular domain (EL3) of the receptor are critical determinants of the host range difference between mice and humans. However, placing these residues in the human homolog confers only partial binding, indicating that other divergent sequences are involved. We sought to determine if the other sequences lie within or outside EL3. Here we report the identification of lysine 234 as another critical residue that influences virus binding and infection, as well as evidence that the unidentified sequences lie outside EL3. Each of the four basic residues in the third extracellular domain were changed to an acidic residue and initially examined in combination with a change at position 235 or position 237. Substitution of lysine 211, 215, or 222 combined with substitution of the critical tyrosine 235 or glutamic acid 237 did not affect virus infection. However, combined substitution of lysine 234, a conserved residue between mice and humans, and tyrosine 235 resulted in a marked decrease in virus infection and binding. A lysine 234 change alone reduced virus binding, contrary to previous observations that at least two of the other four residues must be changed before binding is reduced. Interestingly, there was no decrease in infection when lysine 234 was replaced in combination with glutamic acid 237. This result suggests that residue 234 may act by influencing the local structure of residues 233 to 235, whereas the presence of a glycine at position 236 may prevent this influence from extending to residue 237. With this report, the involvement of all the residues divergent between mice and humans in the third extracellular domain has been ruled out, suggesting that as yet unidentified determinants lie in other extracellular domains.
A Naturally Occurring Substitution in Human Immunodeficiency Virus Tat Increases Expression of the Viral Genome
Authors: Reza Syed M. , Shen Lin-Ming , Mukhopadhyay Rupa , Rosetti Mihaela , Pe'ery Tsafi , Mathews Michael B. 
Published: July 2003

ABSTRACTA natural amino acid substitution in the human immunodeficiency virus type 1 (HIV-1) transcriptional activator Tat increases its activity and compensates for deleterious mutations elsewhere in the Tat protein. Substitution of asparagine for threonine 23 increases Tat transactivation of the HIV-1 promoter and the binding of Tat to the cellular kinase positive transcription elongation factor b (P-TEFb). Of nine other position 23 mutations tested, only the serine substitution retained wild-type activity. Correspondingly, asparagine is the most frequent amino acid at this position in HIV-1 isolates, followed by threonine and serine. Asparagine is prevalent in Tat proteins of viruses in clades A, C, and D, which are major etiologic agents of AIDS. We suggest that selection for asparagine in position 23 confers an advantage to the virus, since it can compensate for deleterious mutations in Tat. It may also support the replication of otherwise less fit drug-resistant viruses and permit the emergence of virulent strains.
Selective enhancement of multipotential hematopoietic progenitors in vitro and in vivo by IL-20
Authors: Liu Ling , Ding Chunjin , Zeng Wei , Heuer Josef G. , Tetreault Jonathan W. , Noblitt Timothy W. , Hangoc Giao , Cooper Scott , Brune Kellie A. , Sharma Ganesh , Fox Niles , Rowlinson Scott W. , Rogers Danise P. , Witcher Derrick R. , Lambooy Peter K. , Wroblewski Victor J. , Miller James R. , Broxmeyer Hal E. 
Published: July 2003

Abstract
In a search for novel growth factors, we discovered that human interleukin-20 (IL-20) enhanced colony formation by CD34+ multipotential progenitors. IL-20 had no effect on erythroid, granulocyte-macrophage, or megakaryocyte progenitors. IL-20 transgenic mice increased the numbers and cell cycling of multipotential but not other progenitors. IL-20 administration to normal mice significantly increased only multipotential progenitor cells, demonstrating that IL-20 significantly influences hematopoiesis, with specificity toward multipotential progenitors. This is the first cytokine with such specificity identified.
Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report
Authors: Lockshin M , Tenedios F , Petri M , McCarty G , Forastiero R , Krilis S , Tincani A , Erkan D , Khamashta M A , Shoenfeld Y 
Published: July 2003

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee’s recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulationfor those who have suffered thrombosis in the absence of atherosclerosis, but recognizesthat developingdata may support the use of antiplateletagents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulationwith warfarin and clinical trials of bosentan, epoprostenol and other new agents.
Gefitinib in Pretreated Non–Small-Cell Lung Cancer (NSCLC): Analysis of Efficacy and Correlation With HER2 and Epidermal Growth Factor Receptor Expression in Locally Advanced or Metastatic NSCLC
Authors: Cappuzzo Federico , Gregorc Vanesa , Rossi Elisa , Cancellieri Alessandra , Magrini Elisabetta , Paties Carlo Terenzio , Ceresoli Giovanni , Lombardo Laura , Bartolini Stefania , Calandri Cesare , De Rosa Marisa , Villa Eugenio , Crinò Lucio 
Published: July 2003

Purpose: To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time. Patients and Methods: Patients with pretreated advanced non–small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry. Results: From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P = .126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2 Conclusion: According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.
DTPACE: An Effective, Novel Combination Chemotherapy With Thalidomide for Previously Treated Patients With Myeloma
Authors: Lee Choon-Kee , Barlogie Bart , Munshi Nikhil , Zangari Maurizio , Fassas Athanasios , Jacobson Joth , van Rhee Frits , Cottler-Fox Michele , Muwalla Firas , Tricot Guido 
Published: July 2003

Purpose: To improve outcome in previously treated patients (at least two cycles of standard therapy) with multiple myeloma, thalidomide was combined with cytotoxic chemotherapy as induction therapy. Patients and Methods: The regimen consisted of 4-days of oral dexamethasone, daily thalidomide, and 4 days of continuous-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide (DTPACE). Response to two cycles of DTPACE for induction was evaluated in 236 patients. Before being treated with DTPACE, 148 patients (63%) had shown progressive disease while receiving standard chemotherapy, and 55 patients (23%) had chromosome 13 abnormalities. Results: The partial remission rate (PR) after two cycles of DTPACE was 32%, with 16% attaining a complete remission (CR) or near-CR (nCR; defined as only immunofixation electrophoresis–positive). Patients with high lactate dehydrogenase (LDH; n = 98) showed a better response than those with normal LDH (n = 138): PR or better, 43% v 27% (P = .01); CR + nCR, 25% v 11% (P = .01). Patients with chromosome 13 abnormalities (n = 55) responded equally well as the other patients (n = 181): PR or better, 35% v 33% (P = .84); CR + nCR, 17% v 15% (P = .73). Patients who received 100% dose of DTPACE for two cycles (n = 115) achieved higher response rates than those with less than 100% dose (n = 121): PR or better, 49% v 17% (P < .0001); CR + nCR, 27% v 6% (P < .0001). Conclusion: Combination therapy of oral dexamethasone and thalidomide with infusional chemotherapy is effective as induction therapy before autotransplantation, especially in patients with high-risk features.
Localized Extremity Soft Tissue Sarcoma: Improved Knowledge With Unchanged Survival Over Time
Authors: Weitz Jürgen , Antonescu Christina R. , Brennan Murray F. 
Published: July 2003

Purpose: The objective of this study was to define whether survival of patients with extremity soft tissue sarcoma (STS), stratified for known risk factors, has improved over the last 20 years. Patients and Methods: From January 1982 to December 2001, 1,706 patients with primary and recurrent STS of the extremities were treated at our institution and were prospectively followed. From this cohort, we selected 1,261 patients who underwent complete macroscopic resection and had one of the following histopathologies: fibrosarcoma, liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, or synovial sarcoma. Median follow-up was 55 months. Patient, tumor, and treatment factors were analyzed as prognostic factors. Results: The 5-year disease-specific actuarial survival was 79% (78% for patients treated from 1982 to 1986, 79% for patients treated from 1986 to 1991, 79% for patients treated from 1992 to 1996, and 85% for patients treated from 1997 to 2001; P = not significant). For high-risk patients (high-grade, > 10 cm, deep tumors; n = 247), 5-year disease-specific survival was 51% (50% for patients treated from 1982 to 1986, 45% for patients treated from 1986 to 1991, 52% for patients treated from 1992 to 1996, and 61% for patients treated from 1997 to 2001; P = not significant). Tumor depth, size, grade, microscopic margin status, patient age, presentation status (primary tumor versus local recurrence), location (proximal versus distal), and certain histopathologic subtypes were significant prognostic factors for disease-specific survival on multivariate analysis; however, time period of treatment was not. Conclusion: Prognosis of patients with extremity STS, stratified for known risk factors, has not improved over the last 20 years, indicating that current therapy has reached the limits of efficacy.
Oxaliplatin With Weekly Bolus Fluorouracil and Low-Dose Leucovorin as First-Line Therapy for Patients With Colorectal Cancer
Authors: Hochster Howard , Chachoua Abraham , Speyer James , Escalon Juliette , Zeleniuch-Jacquotte Anne , Muggia Franco 
Published: July 2003

Purpose: To determine the activity of biweekly oxaliplatin, combined with weekly bolus fluorouracil (FU) and low-dose leucovorin (LV) chemotherapy (bFOL), as first-line therapy for patients with metastatic colorectal cancer. Patients and Methods: Patients with measurable metastatic colorectal cancer; no previous therapy for advanced disease (adjuvant therapy allowed if >6 months since completion); and performance status 0, 1, or 2 were eligible and were treated with oxaliplatin 85 mg/m2 days 1 and 15 plus LV 20 mg/m2 over 10 to 20 minutes, followed by a 500 mg/m2 bolus dose of FU on days 1, 8, and 15 every 28 days. Patients underwent response evaluation by computed tomographic scan every 2 months. Results: Forty-two patients were entered, and 41 patients were treated, including 20 men and 22 women, nine with previous adjuvant chemotherapy and four with radiation therapy. Three patients achieved complete response, and 23 patients achieved partial response, for a response rate of 63% (95% CI, 49% to 78%). Major toxicities included cumulative neuropathy grade 2 (24%) and grade 3 (12%; requiring discontinuation of oxaliplatin), diarrhea grade 3 to 4 (29%) and grade 3 to 4 hematologic toxicity (10%). Median time to progression was 9.0 months (95% confidence interval, 7.1 to 10.8 months) with median survival of 15.9 months (95% confidence interval, 11.4 to 19.7 months). Conclusion: The bFOL regimen seems to have activity comparable to be infusional programs of FU combined with oxaliplatin. Prospective trials are warranted to determine the relative merits of this schedule compared with the currently indicated schedules.
Long-Term Toxicity After Definitive Chemoradiotherapy for Squamous Cell Carcinoma of the Thoracic Esophagus
Authors: Ishikura Satoshi , Nihei Keiji , Ohtsu Atsushi , Boku Narikazu , Hironaka Shuichi , Mera Kiyomi , Muto Manabu , Ogino Takashi , Yoshida Shigeaki 
Published: July 2003

Purpose: To assess the long-term toxicity after definitive chemoradiotherapy (CRT) for squamous cell carcinoma (SCC) of the esophagus. Patients and Methods: Patients newly diagnosed with SCC of the esophagus and treated with definitive CRT between 1992 and 1999 in our institution were recruited from our database on the basis of the following criteria: age ≤ 75 years, performance status (PS; based on the Eastern Cooperative Oncology Group scale) 0 to 2, and clinical tumor-node-metastasis system stage I to IVA. The CRT consisted of two cycles of cisplatin 40 mg/m2 on days 1 and 8, and continuous infusion of fluorouracil 400 mg/m2/d on days 1 to 5 and 8 to 12, repeated every 5 weeks with concurrent radiotherapy of 60 Gy in 30 fractions. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme was adopted. Results: A total of 139 patients were recruited, and their characteristics were as follows: median age, 62 years (range, 38 to 75 years); 121 males and 18 females; 96 patients PS 0, 42 patients PS 1, and one patient PS 2; 15 patients T1, 11 patients T2, 60 patients T3, and 53 patients T4; and 101 patients M0, 38 patients M1a. With a median follow-up of 53 months, the median survival time and 5-year survival rate were 21 months and 29%, respectively. Of 78 patients with complete remission, two patients died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in eight patients, seven patients, and one patient, respectively; heart failure in zero, zero, and two patients; pleural effusion in seven, eight, and zero patients; and radiation pneumonitis in one patient, three patients, and zero patients, respectively. Conclusion: Definitive CRT for SCC of the esophagus is effective with substantial toxicities. Additional investigation to minimize the normal tissue toxicities is warranted.
Cluster Analysis of p53 and Ki67 Expression, Apoptosis, Alpha-Fetoprotein, and Human Chorionic Gonadotrophin Indicates a Favorable Prognostic Subgroup Within the Embryonal Carcinoma Germ Cell Tumor
Authors: Mazumdar Madhu , Bacik Jennifer , Tickoo Satish K. , Dobrzynski Deborah , Donadio Alessia , Bajorin Dean , Motzer Robert , Reuter Victor , Bosl George J. 
Published: July 2003

Purpose: The prognostic information provided by alpha-fetoprotein and human chorionic gonadotrophin in the management of germ cell tumor (GCT) patients is a biochemical reflection of tumor differentiation. Ki67, p53, and apoptosis have been found to be related to proliferation (Ki67), cell death (p53, apoptosis), and possibly differentiation chemoresistance (p53). We sought to determine whether simultaneous expression of one or more of these markers could identify clinically relevant subgroups of patients with nonseminomatous GCT (NSGCT). Patients and Methods: These five marker values were obtained for 95 previously untreated patients with embryonal carcinoma with or without other germ cell components. A multivariate cluster analysis was performed to identify patients with similar marker patterns. Results: One prominent cluster (n = 37; 36 testis retroperitoneum), consisting of 26 (70%) good-risk (GR), nine (24%) intermediate-risk (IR), and two (6%) poor-risk (PR) patients, as defined by the International Germ Cell Consensus Cancer Group (IGCCCG), was observed. The 5-year survival of the prominent cluster (with 30% IR/PR patients) was 94% (95% confidence interval [CI], 86% to 100%), which is comparable to the 91% (95% CI, 89% to 93%) 5-year survival of the IGCCCG GR patients. IGCCCG risk status (P = .005) and cluster affiliation (P = .04) were independent predictors of outcome with hazard ratios of 5.0 (95% CI, 1.6 to 15.4) and 4.6 (95% CI, 1.04 to 20.1), respectively. Conclusion: These results suggest that there is a subgroup of NSGCT patients with embryonal carcinoma (with or without other histologies) with a specific tumor biology profile (high Ki67, low apoptosis, and low p53) whose survival is better than that of the overall patient group. The unexpectedly good outcome for the prominent cluster and independent-risk status suggest that subgroups of GCT reflecting different abilities to respond to treatment exist within IGCCCG prognostic categories.
HER-2 Expression and Cell Proliferation: Prognostic Markers in Patients With Node-Negative Breast Cancer
Authors: Volpi Annalisa , Nanni Oriana , De Paola Franca , Granato Anna Maria , Mangia Annita , Monti Franco , Schittulli Francesco , De Lena Mario , Scarpi Emanuela , Rosetti Paola , Monti Manlio , Gianni Lorenzo , Amadori Dino , Paradiso Angelo 
Published: July 2003

Purpose: We analyzed the clinical relevance of HER-2 expression, widely investigated in breast cancer but with contradictory results, in the largest case series of node-negative breast cancer patients investigated to date. Patients and Methods: The pure prognostic value of HER-2 expression was investigated in 529 patients treated with locoregional therapy alone until early relapse. Proliferative activity was evaluated as [ 3 H]thymidine labeling index and HER-2 expression by immunohistochemistry. All biologic determinations were conducted within the context of an intra- and interlaboratory National Quality Control Program. Results: HER-2 expression was not related to relapse-free survival in the overall series but was a significant discriminant of prognosis in the subgroup of patients with rapidly proliferating tumors. Six-year rate of relapse was 40% for patients with highly (≥30%) positive tumors and 26% for those with weakly HER-2-expressing tumors (P = .039). Conclusion: HER-2 expression in association with proliferative activity identifies a subgroup of node-negative breast cancer patients with the worst prognosis, who are candidates for specific intensive adjuvant therapy.
Intestinal Non-Hodgkin’s Lymphoma: A Multicenter Prospective Clinical Study From the German Study Group on Intestinal Non-Hodgkin’s Lymphoma
Authors: Daum Severin , Ullrich Reiner , Heise Walter , Dederke Bettina , Foss Hans-Dieter , Stein Harald , Thiel Eckhard , Zeitz Martin , Riecken Ernst-Otto 
Published: July 2003

Purpose: Intestinal non-Hodgkin’s lymphomas are not well characterized. We therefore studied prospectively their clinical features and response to standardized therapy. Patients and Methods: Fifty-six patients with primary intestinal lymphoma were included in a prospective, nonrandomized multicenter study. Lymphoma resection was recommended and staging was performed according to the Ann Arbor classification. Patients were scheduled to receive six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy, and at stages EIII to EIV, they received additional involved-field radiotherapy. Corticosteroids were used in patients who could not receive chemotherapy. Results: Thirty-five patients had intestinal T-cell lymphoma (ITCL), 21 patients had intestinal B-cell lymphoma (IBCL; 18 diffuse large-cell lymphomas, two marginal-cell lymphomas, and one follicle-center lymphoma). Thirty-four patients at stages EI to EII (14 ITCL and 20 IBCL) and nine patients at stages EIII to EIV (all ITCL) received chemotherapy. No patient in stages EIII to EIV received radiotherapy, because death occurred in 12 of 14 patients. Two-year cumulative survival in patients with IBCL was 94% (95% CI, 82% to 100%) and higher than in patients with ITCL (28% [95% CI, 13% to 43%]; P < .0001), even when only stages EI to EII were considered (ITCL, 37.5% [95% CI, 16.5% to 58.5%]; P < .0001). IBCL patients compared with ITCL patients were at lower lymphoma stages (P < .01), had higher Karnofsky status (P < .005), had intestinal perforation less often (P < .05), required emergency operation less often (P < .05), received CHOP (P < .05) more often, and reached complete remission (P < .0005) more frequently. Conclusion: IBCL patients at stages EI and EII respond well to chemotherapy, but the prognosis and treatment of ITCL patients is unsatisfactory.