bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAX3-FKHR and PAX7-FKHR Gene Fusions Are Prognostic Indicators in Alveolar Rhabdomyosarcoma: A Report From the Children’s Oncology Group
Authors: Sorensen Poul H.B. , Lynch James C. , Qualman Stephen J. , Tirabosco Roberto , Lim Jerian F. , Maurer Harold M. , Bridge Julia A. , Crist William M. , Triche Timothy J. , Barr Frederic G. 
Published: October 2002

PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity of gene fusion detection in a large cohort of RMS patients and to evaluate whether these alterations influence clinical outcome in ARMS. PATIENTS AND METHODS: We determined PAX3-FKHR or PAX7-FKHR fusion status in 171 childhood rhabdomyosarcoma (RMS) patients entered onto the Intergroup Rhabdomyosarcoma Study IV, including 78 ARMS patients, using established reverse transcriptase polymerase chain reaction assays. All patients received central pathologic review and were treated using uniform protocols, allowing for meaningful outcome analysis. We examined the relationship between gene fusion status and clinical outcome in the ARMS cohort. RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were detected in 55% and 22% of ARMS patients, respectively; 23% were fusion-negative. All other RMS patients lacked transcripts, confirming the specificity of these alterations for ARMS. Fusion status was not associated with outcome differences in patients with locoregional ARMS. However, in patients presenting with metastatic disease, there was a striking difference in outcome between PAX7-FKHR and PAX3-FKHR patient groups (estimated 4-year overall survival rate of 75% for PAX7-FKHR v 8% for PAX3-FKHR; P = .0015). Multivariate analysis demonstrated a significantly increased risk of failure (P = .025) and death (P = .019) in patients with metastatic disease if their tumors expressed PAX3-FKHR. Among metastatic ARMS, bone marrow involvement was significantly higher in PAX3-FKHR–positive patients. CONCLUSION: Not only are PAX-FKHR fusion transcripts specific for ARMS, but expression of PAX3-FKHR and PAX7-FKHR identifies a very high-risk subgroup and a favorable outcome subgroup, respectively, among patients presenting with metastatic ARMS.
Hepatocellular Carcinoma in Children: Results of the First Prospective Study of the International Society of Pediatric Oncology Group
Authors: Czauderna P. , Mackinlay G. , Perilongo G. , Brown J. , Shafford E. , Aronson D. , Pritchard J. , Chapchap P. , Keeling J. , Plaschkes J. , Otte J.B. 
Published: October 2002

PURPOSE: To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncology’s first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty patients (51%) never became operable. Overall survival at 5 years was 28%, and event-free survival was 17%. Most deaths resulted from tumor progression (26 of 28). Presence of metastases and pretreatment extent of disease system grouping at diagnosis had an adverse influence on overall survival in multivariate analysis. CONCLUSION: Survival for pediatric HCC patients is significantly inferior to that for children with hepatoblastoma. Complete tumor excision remains the only realistic chance of cure, although it is often prevented by advanced disease. The presence of metastases is the most potent predictor of poor prognosis. A prospective worldwide cooperation in the field of pediatric HCC should be encouraged to look for novel therapeutic concepts.
High Response Rate to Cisplatin/Etoposide Regimen in Childhood Low-Grade Glioma
Authors: Massimino Maura , Spreafico Filippo , Cefalo Graziella , Riccardi Riccardo , Tesoro-Tess John David , Gandola Lorenza , Riva Daria , Ruggiero Antonio , Valentini Laura , Mazza Elena , Genitori Lorenzo , Di Rocco Concezio , Navarria Piera , Casanova Michela , Ferrari Andrea , Luksch Roberto , Terenziani Monica , Balestrini Maria Rosa , Colosimo Cesare , Fossati-Bellani Franca 
Published: October 2002

PURPOSE: The aim of this study was to avoid radiotherapy and to induce an objective response in children with low-grade glioma (LGG) using a simple chemotherapy regimen based on cisplatin and etoposide. PATIENTS AND METHODS: Thirty-four children (median age, 45 months) with unresectable LGG were treated with 10 monthly cycles of cisplatin (30 mg/m2/d on days 1 to 3) and etoposide (150 mg/m2/d on days 1 to 3). Tumor originated in the visual pathway in 29 patients, in the temporal lobe in two, in the frontal lobe in two, and in the spine in one. Eight children were affected by neurofibromatosis type 1. Objective tumor response and toxicity were evaluated by magnetic resonance imaging and neurologic and functional tests at 3-month intervals. RESULTS: An objective response was obtained in 24 (70%) of 34 patients, whereas the others had stable disease. None of the children were electively irradiated. In 31 previously untreated children, overall survival was 100% and progression-free survival was 78% at 3 years, with a median follow-up of 44 months. Acute toxicity was unremarkable; 28% patients evaluated for acoustic neurotoxicity revealed a loss of perception of high frequencies. CONCLUSION: Cisplatin and etoposide combined treatment is one of the most active regimens for LGG in children and allows avoidance of radiotherapy in the vast majority of patients.
Doxorubicin and Paclitaxel Versus Doxorubicin and Cyclophosphamide as First-Line Chemotherapy in Metastatic Breast Cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial
Authors: Biganzoli L. , Cufer T. , Bruning P. , Coleman R. , Duchateau L. , Calvert A.H. , Gamucci T. , Twelves C. , Fargeot P. , Epelbaum R. , Lohrisch C. , Piccart M.J. 
Published: October 2002

PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m2 as an intravenous bolus plus paclitaxel 175 mg/m2 as a 3-hour infusion) or AC (doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m2) and cyclophosphamide (750 mg/m2) dose escalation was planned at cycle 2 if no grade ≥ 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life. RESULTS: A median number of six cycles were delivered in the two treatment arms. The relative dose-intensity and delivered cumulative dose of doxorubicin were lower in the AT arm. Dose escalation was only possible in 17% and 20% of the AT and AC patients, respectively. Median PFS was 6 months in the two treatments arms. RR was 58% versus 54%, and median OS was 20.6 versus 20.5 months in the AT and AC arms, respectively. The AT regimen was characterized by a higher incidence of febrile neutropenia, 32% versus 9% in the AC arm. CONCLUSION: No differences in the efficacy study end points were observed between the two treatment arms. Treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen
Prognostic Impact of Micrometastatic Tumor Cells in the Lymph Nodes and Bone Marrow of Patients With Completely Resected Stage I Non–Small-Cell Lung Cancer
Authors: Osaki Toshihiro , Oyama Tsunehiro , Gu Chun-Dong , Yamashita Toshihiro , So Tomoko , Takenoyama Mitsuhiro , Sugio Kenji , Yasumoto Kosei 
Published: October 2002

PURPOSE: This study was designed to substantiate the prognostic impact of occult micrometastatic tumor cells in the lymph nodes (LNs) and bone marrow (BM) in stage I non–small-cell lung cancer (NSCLC) patients using cytokeratin (CK) as a micrometastatic marker and the relationship between the micrometastases in the LNs and BM. PATIENTS AND METHODS: A total of 2,432 hilar and mediastinal LNs were removed during surgery from 115 patients with completely resected stage I NSCLC. The LNs were analyzed for micrometastasis using immunohistochemistry with the biclonal anti-CK antibody AE1/AE3. BM aspirates from 115 patients were immunocytochemically stained with the monoclonal anti-CK antibody CK2. RESULTS: CK-positive (CK+) cells were detected in 42 (1.7%) of 2,432 LNs, in 32 (27.8%) of 115 patients, and in 32 (27.8%) of 115 BM aspirates. There was no relationship between the frequencies of CK+ cells in the LNs and in the BM. The patients with CK+ cells in the LNs had a poor prognosis by both univariate (P = .008) and multivariate analyses (P = .01), whereas the presence of CK+ cells in the BM did not allow prediction of survival (P = .32). The prognostic impact of LNs micrometastasis was independent even after adjusting for the status of BM micrometastasis. CONCLUSION: The detection of lymph nodal micrometastatic tumor cells provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients.
ChlVPP/EVA Hybrid Versus the Weekly VAPEC-B Regimen for Previously Untreated Hodgkin’s Disease
Authors: Radford J. A. , Rohatiner A. Z.S. , Ryder W. D.J. , Deakin D. P. , Barbui T. , Lucie N. P. , Rossi A. , Dunlop D. J. , Cowan R. A. , Wilkinson P. M. , Gupta R. K. , James R. D. , Shamash J. , Chang J. , Crowther D. , Lister T. A. 
Published: October 2002

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks’ duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months’ treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin’s disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score ≤ 2, nonbulky disease). CONCLUSION: Apart from possibly in the best-prognosis group, where results are equivalent, ChlVPP/EVA hybrid produces significantly better FFP, EFS, and OS than VAPEC-B in patients with previously untreated Hodgkin’s disease.
Comparing the Costs of Radiation Therapy and Radical Prostatectomy for the Initial Treatment of Early-Stage Prostate Cancer
Authors: Burkhardt Jeffrey H. , Litwin Mark S. , Rose Christopher M. , Correa Roy J. , Sunshine Jonathan H. , Hogan Christopher , Hayman James A. 
Published: October 2002

PURPOSE: Radical prostatectomy and external-beam radiation are the most common treatments for localized prostate cancer. Given the absence of clinical consensus in favor of one treatment or the other, relative costs may be a significant factor. This study compares the direct medical costs during the month before and 9 months after diagnosis for patients treated primarily with external-beam radiation or radical prostatectomy for early-stage prostate cancer. METHODS: Patients age 65 or older and coded by the Surveillance, Epidemiology, and End Results (SEER) registry as having been diagnosed with adenocarcinoma of the prostate treated primarily with external-beam radiation or radical prostatectomy during 1992 and 1993 were identified. The initial treatment costs, as measured by Medicare-approved payment amounts, for each strategy were analyzed using linked SEER-Medicare claims data after adjusting for differences in comorbidity and age. An intent-to-treat analysis was also performed to adjust for differences in staging between the two groups. RESULTS: For patients in the treatment-received analysis, the average costs were significantly different; $14,048 (95% confidence interval [CI], $13,765 to $14,330) for radiation therapy and $17,226 (95% CI, $16,891 to $17,560) for radical prostatectomy (P < .001). The average costs for patients in the intent-to-treat analysis were also significantly less for radiation therapy patients ($14,048; 95% CI, $13,765 to $14,330) than for those who underwent radical prostatectomy ($17,516; 95% CI, $17,195 to $17,837; P < .001). CONCLUSION: For patients with early-stage prostate cancer, average costs during the initial treatment interval were at least 23% greater for radical prostatectomy than for external-beam radiation. Major limitations of the research include not studying costs after the initial treatment interval and questionable current applicability, given changes in management of early prostate cancer.
Monoclonal anti-epidermal growth factor receptor (ior EGF/r3) antibody pharmacokinetic studies on nude mice I: a radio-receptor analysis applied to drug serum quantification
Authors: Fernández-Sánchez E , Ducongé J , Castillo R , Garcia I , Beausoleil I , Macías A 
Published: October 2002

Abstract
Due to its antagonistic properties upon ligand-epidermal growth factor receptor (EGFr) interaction, the monoclonal antibody anti-EGFr ior EGF/r3 is considered a potential therapeutic agent against several epithelium-derived tumours. This paper affords further analysis of the relevant corporal interaction of this monoclonal antibody in terms of its pharmacodynamic properties, using nude mice, following a single bolus intravenous dose administration. The radio-receptor assay allows quantification of the serum ior EGF/r3 level. The dose selection procedure, according to the Kolmogorov-Smirnov test, suggested using doses of 12.5–16 mg kg−1 for pharmacokinetic assessments. The experimental data were best fitted to a biexponential function (r2 = 0.985), through the classical two-compartment open modelling approach. The model selection was corroborated by the AKAIKE information criteria, and also the SCHWARTZ and ESTRIPtest were used. The estimated pharmacokinetic parameters (e.g. = 34.65 h, Vc = 2.84 mL, Vss = 4.21 mL and CL = 0.09 mL h−1) bear out the strategies for the evaluation of the therapeutic application of this drug. Finally, the radio-receptor analysis has provided a rationale for the proposed serum monoclonal antibody ior EGF/r3 quantification to characterize its concentration-time course.
Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery
Authors: Goldberg Eugene P , Hadba Ahmad R , Almond Brett A , Marotta James S 
Published: October 2002

Abstract
The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical findings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a fine line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well defined primary lesions i.e. breast, colorectal, lung, prostate, and skin. There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemo-immunotherapy almost 20 years ago (McLaughlin & Goldberg 1983), there have been few comprehensive reviews of this field; only one of broad scope (Brincker 1993), three devoted specifically to gliomas (Tomita 1991; Walter et al. 1995; Haroun & Brem 2000), one on hepatomas (Venook 2000), one concerning veterinary applications (Theon 1998), and one older review of dermatological applications (Goette 1981). However, none have shed light on practical opportunities for combining intratumoral therapy with subsequent surgical resection. Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. fine needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy.
In-vitro distribution of terbinafine in rat and human blood
Authors: Yeganeh Mahboubeh Hosseini , McLachlan Andrew J 
Published: October 2002

Abstract
The association of drugs with plasma lipoproteins has the potential to influence drug action and disposition. In this study, the uptake and distribution of the lipophilic antifungal drug, terbinafine, was investigated in rat and human blood and plasma. Fresh plasma was incubated with terbinafine (200–1000 ng mL−1), then subjected to vertical spin density gradient ultra-centrifugation to separate protein fractions. Theconcentrations of terbinafine in each fraction was determined using a validated reversed-phase HPLC method. The association of terbinafine with very-low-density lipoproteins (15.5 ± 7.1 % of total concentration) in human plasma was significantly lower than that associated with fractions containing soluble proteins (28.0 ± 6.2 %), high-(26.8 ± 7.7 %) and low-density lipoproteins (31.6 ± 4.6%). In rats terbinafine was found to be distributed evenly through plasma protein fractions. The association of terbinafine in lipoproteins was independent of concentration (over the range 200–1000 ng mL−1) and species. The distribution of terbinafine was examined in human and rat blood and the blood-to-plasma ratio of terbinafine was 0.70 ± 0.09 and 1.01 ± 0.20, respectively, indicating higher association of terbinafine with plasma components than erythrocytes in humans. This study suggests that in humans and rats, terbinafine associates with a number of plasma proteins independently of terbinafine concentration. Alteration in plasma lipoprotein concentrations are therefore likely to influence terbinafine binding in blood and distribution in the body.
Comparative inhibitory effects of niflumic acid and novel synthetic derivatives on the rat isolated stomach fundus
Authors: Criddle David N , Meireles Ana Vanesca P , Macêdo Liana B , Leal-Cardoso José H , Scarparo Henrique C , Jaffar Mohammed 
Published: October 2002

Abstract
Novel derivatives of 2-[3-(trifluoromethyl)-analino]nicotinic acid (niflumic acid) were synthesized. The compounds were compared for their inhibitory effects on 5-hydroxytryptamine (5-HT)- and KCl-induced contraction of the rat fundus. The aim was to assess structure-activity relationships regarding the selectivity and potency of these compounds. Niflumic acid (1–100 μM) concentration-dependently inhibited 5-HT-induced tonic contractions with an IC50 value (concentration reducing the control contractile response by 50%, calculated from semilog graphs) of 0.24 × 10−4 M (n = 9). In contrast, it was significantly less potent at inhibiting KCl-induced responses (IC50 = 1.49 × 10−4 M, n = 9). The methyl ester (NFAme) and amido (NFAm) analogues showed no selectivity between 5-HT- and KCl-induced contractions with IC50 values of 1.64 × 10−4 M (n = 8) and 1.87 × 10−4 M (n = 9) for 5-HT responses, and 2.61 × 10−4 M (n = 8) and 2.55 × 10−4 M (n = 7) for KCl-induced responses, respectively. Our results suggest that alteration of the carboxylic acid moiety of niflumic acid reduces the selectivity and potency of its inhibitory action on 5-HT-induced contractile responses of the rat fundus, possibly via a reduced interaction with calcium-activated chloride channels.
In-vitro cytotoxic/cytostatic activity of anionic liposomes containing vinblastine against leukaemic human cell lines
Authors: Maswadeh H , Demetzos C , Dimas K , Loukas Y L , Georgopoulos A , Mavromoustakos T , Papaioannou G Th 
Published: October 2002

Abstract
Liposomes prepared from lipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) with cholesterol were used to investigate the percentage of vinblastine encapsulation and the influence of lipid composition on the retention properties of vinblastine in buffer as well as in cell culture medium. Differential scanning calorimetry (DSC) was applied, to study the effect of cholesterol on the phase transition temperature and on the ΔH of the two liposome formulations. The cytotoxic and cytostatic activity of the liposome-encapsulated vinblastine was also examined against six leukaemic human cell lines. The results showed that encapsulation of vinblastine into liposomes was greater than 98% with a drug-phospholipid molar ratio of 0.13-0.18. The major improvement in vinblastine retention in buffer as well as in culture medium was achieved by employing DPPG. The DSC data showed that vinblastine exerted a more perturbing effect in DPPC-cholesterol bilayers than in DPPG-cholesterol bilayers and this may explain their lower retention time. The 50% growth-inhibiting (GI50) and cytostatic (TGI) activity of liposomal vinblastine did not seem to be affected by the type of the liposome while the 50 % cytotoxic activity (LC50) was affected in four out of the six cell lines tested. The parameters GI50, TGI and LC50 were estimated according to the instructions given by the NCI.