bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Efficacy of Transcatheter Arterial Chemoembolization as Compared With Hepatic Resection in Hepatocellular Carcinoma Patients With Compensated Liver Function in a Hepatitis B Virus–Endemic Area: A Prospective Cohort Study
Authors: Lee Hyo-Suk , Kim Kang Mo , Yoon Jung-Hwan , Lee Tae-Rim , Suh Kyung Suk , Lee Kuhn Uk , Chung Jin Wook , Park Jae Hyung , Kim Chung Yong 
Published: November 2002

PURPOSE: Identifying a special subgroup of hepatocellular carcinoma (HCC) patients who may benefit from transcatheter arterial chemoembolization (TACE) when compared with the standard treatment of hepatic resection (HR) warrants research in Asian countries. PATIENTS AND METHODS: From January 1993 to December 1994, 182 patients with operable HCC (Child-Pugh class A and International Union Against Cancer [UICC] stage T1-3N0M0) were enrolled. After initial TACE and lipiodol computed tomography, 91 received HR and 91, who refused the operation, received repeated sessions of TACE. After stratification according to the tumor stage (UICC and Cancer of the Liver Italian Program [CLIP]) and lipiodol retention pattern, the survival rates of the two treatment groups were compared. The median follow-up period was 83 months. RESULTS: As of December 31, 2000, 48 patients who underwent HR and 68 patients who underwent TACE had died. In a subgroup analysis according to tumor stage, the HR group survival rate was significantly higher than the TACE group in both UICC T1-2N0M0 (P = .0058) and CLIP 0 (P = .0027) subgroups. However, there was no significant difference in either UICC T3N0M0 (P = .7512) or CLIP 1-2 (P = .5366) subgroups. Even in patients with UICC T1-2N0M0 HCC, when lipiodol was compactly retained, the survival rate of the HR group was comparable to that of the TACE group (P = .0596). CONCLUSION: TACE proved to be as effective as HR in the subpopulations with UICC T3N0M0 or CLIP 1-2 HCC and adequate liver function, and even with UICC T1-2N0M0 HCC when lipiodol was compactly retained in the tumor. In such cases, the choice of treatment modality between TACE and HR may be left to the patient’s preference.
Function and Health Status Outcomes in a Randomized Trial Comparing Preoperative and Postoperative Radiotherapy in Extremity Soft Tissue Sarcoma
Authors: Davis A.M. , O’Sullivan B. , Bell R.S. , Turcotte R. , Catton C.N. , Wunder J.S. , Chabot P. , Hammond A. , Benk V. , Isler M. , Freeman C. , Goddard K. , Bezjak A. , Kandel R.A. , Sadura A. , Day A. , James K. , Tu D. , Pater J. , Zee B. 
Published: November 2002

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P < .01), TESS (69.8 v 60.6, P = .01), and SF-36 bodily pain (67.7 v 58.5, P = .03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.
Safety and Pharmacokinetic Effects of TNP-470, an Angiogenesis Inhibitor, Combined With Paclitaxel in Patients With Solid Tumors: Evidence for Activity in Non–Small-Cell Lung Cancer
Authors: Herbst Roy S. , Madden Timothy L. , Tran Hai T. , Blumenschein George R. , Meyers Christina A. , Seabrooke Lee F. , Khuri Fadlo R. , Puduvalli Vinay K. , Allgood Victoria , Fritsche Herbert A. , Hinton Leslie , Newman Robert A. , Crane Elizabeth A. , Fossella Frank V. , Dordal Margaret , Goodin Thomas , Hong Waun Ki 
Published: November 2002

PURPOSE: Preclinical studies suggested that the antiangiogenic agent TNP-470 was synergistic with cytotoxic therapy. TNP-470 was administered with paclitaxel to adults with solid tumors to define the safety and optimal dose of the combination regimen and to assess pharmacokinetic interactions.PATIENTS AND METHODS: Thirty-two patients were enrolled chronologically onto one of two treatment arms. Arm A involved a fixed TNP-470 dose with escalating doses of paclitaxel, and Arm B involved a fixed paclitaxel dose with escalating doses of TNP-470. Paclitaxel and TNP-470 pharmacokinetics were evaluated along with toxicity.RESULTS: The combination of TNP-470 administered at 60 mg/m2three times per week and paclitaxel 225 mg/m2administered over 3 hours every 3 weeks was defined as both the maximum-tolerated dose and the optimal dose. Myelosuppression was similar to that expected with paclitaxel alone. Mild to moderate neurocognitive impairment was observed; however, the majority of changes were subclinical and reversible as determined by prestudy and poststudy neuropsychiatric test results. A clinically insignificant decrease of paclitaxel clearance was observed for the combination. Median survival for all patients was 14.1 months. Partial responses were reported in eight (25%) of 32 patients and in six (38%) of 16 patients with NSCLC, 60% of whom had received prior chemotherapy.CONCLUSION: The combination of TNP-470 and paclitaxel, each at full single-agent dose, seems well tolerated, with minimal pharmacokinetic interaction between the two agents. Further studies of TNP-470 with chemotherapy regimens are warranted in NSCLC and other solid tumors.
Randomized Study to Evaluate the Use of High-Dose Therapy as Part of Primary Treatment for “Aggressive” Lymphoma
Authors: Kaiser Ulrich , Uebelacker Irmgard , Abel Ulrich , Birkmann Josef , Trumper Lorenz , Schmalenberg Harald , Karakas Tunca , Metzner Bernd , Hossfeld Dieter K. , Bischoff Helge G. , Franke Astrid , Reiser Marcel , Muller Peter , Mantovani Luisa , Grundeis Marc , Rothmann Frank , von Seydewitz Cay-Uwe , Mesters Rolf M. , Steinhauer Ernst U. , Krahl Dorothea , Schumacher Kurt , Kneba Michael , Baudis Michael , Schmitz Norbert , Pfab Rudiger , Koppler Hubert , Parwaresch Reza , Pfreundschuh Michael , Havemann Klaus 
Published: November 2002

PURPOSE: This trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group compares the use of high-dose therapy (HDT) as part of primary treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide followed by involved-field (IF) radiotherapy in a randomized, multicenter, phase III study. PATIENTS AND METHODS: Three hundred twelve patients with “aggressive” non-Hodgkin’s lymphoma aged ≤ 60 years with elevated serum lactate dehydrogenase levels were included from 1990 to 1997. Patients with at least a minor response after two cycles of CHOEP (CHOP + etoposide 3 × 100 mg/m2) were to receive three further cycles of CHOEP followed by IF radiotherapy (arm A) or one further cycle of CHOEP followed by autologous stem-cell transplantation and IF radiotherapy (arm B). RESULTS: Among 158 patients randomized to arm B, 103 (65%) received HDT. The complete remission rate at the end of treatment was 62.9% in arm A and 69.9% in arm B. With a median observation time of 45.5 months, overall survival for all 312 patients was 63% after 3 years (63% for arm A, 62% for arm B; P = .68). Event-free survival was 49% for arm A versus 59% for arm B (P = .22). Relapse in arm B was associated with a significantly worse survival rate than relapse in arm A (P < .05). Relapse after HDT occurred early (median interval, 3 months). Six patients developed secondary neoplasia, three in arm A and three in arm B. CONCLUSION: Results of the randomized trial comparing CHOP-like chemotherapy with early HDT do not support the use of HDT with carmustine, etoposide, cytarabine, and melphalan following shortened standard chemotherapy.
BRCA1/2 Genetic Testing in the Community Setting
Authors: Chen Wendy Y. , Garber Judy E. , Higham Suzanne , Schneider Katherine A. , Davis Katie B. , Deffenbaugh Amie M. , Frank Thomas S. , Gelman Rebecca S. , Li Frederick P. 
Published: November 2002

PURPOSE: BRCA1/2 genetic testing has been commercially available in the United States since 1996. Most published reports described BRCA1/2 testing as research studies at large academic centers, but less is known about testing in the community. This study evaluates the process and early outcomes of BRCA1/2 genetic testing as a clinical service in the community setting. METHODS: Surveys were mailed to women in the United States whose health care providers ordered BRCA1/2 genetic testing from Myriad Genetic Laboratories from August 1998 through July 2000. Women tested at 149 large academic centers were excluded. Main outcome measures were demographic characteristics, recall of and satisfaction with the genetic testing process, and likelihood of pursuing cancer prevention strategies. RESULTS: Among the 646 respondents, 414 (64%) had a personal history of cancer and 505 (78%) had at least one first-degree relative with breast and/or ovarian cancer. Most subjects (82%) recalled discussions of informed consent before testing (median time, 30 minutes). Genetic results were conveyed during an office visit (57%), by telephone (39%), or by mail (3%). More than 75% of respondents were “very satisfied with the counseling received.” Cancer-free subjects with a germline mutation were more likely to consider prevention strategies after receiving the genetic results. CONCLUSION: Virtually all respondents had a personal and/or family history of breast/ovarian cancer. Although pretest and posttest communications were not standardized, overall satisfaction with clinical breast cancer genetic testing was high. Additional follow-up will provide data on future cancer prevention practices and cancer incidence.
Randomized Discontinuation Design: Application to Cytostatic Antineoplastic Agents
Authors: Rosner Gary L. , Stadler Walter , Ratain Mark J. 
Published: November 2002

PURPOSE: Propose a phase II study design to evaluate the activity of a putative cytostatic agent, acknowledging heterogeneity of tumor growth rates in the population of patients. METHODS: In the setting of renal cell carcinoma, some patients’ tumors will grow slowly naturally. An appropriate design has to distinguish antiproliferative activity attributable to the novel agent from indolent disease. We propose a randomized discontinuation design that initially treats all patients with the study agent (stage 1) and then randomizes in a double-blind fashion to continuing therapy or placebo only those patients whose disease is stable (stage 2). This design allows the investigators to determine if apparent slow tumor growth is attributable to the drug or to selection of patients with naturally slow-growing tumors. RESULTS: By selecting a more homogeneous population, the randomized portion of the study requires fewer patients than would a study randomizing all patients at entry. The design also avoids potential confounding because of heterogeneous tumor growth. Because the two randomly assigned treatment groups each comprise patients with apparently slow growing tumors, any difference between the groups in disease progression after randomization is more likely a result of the study drug and less likely a result of imbalance with respect to tumor growth rates. Stopping rules during the initial open-label stage and the subsequent randomized trial stage allow one to reduce the overall sample size. Expected average tumor growth rate is an important consideration when deciding the duration of follow-up for the two stages. CONCLUSION: The randomized discontinuation design is a feasible alternative phase II study design for determining activity of possibly cytostatic anticancer agents.
Children From Ethnic Minorities Have Benefited Equally as Other Children From Contemporary Therapy for Rhabdomyosarcoma: A Report From the Intergroup Rhabdomyosarcoma Study Group
Authors: Baker K. Scott , Anderson James R. , Lobe Thom E. , Wharam Moody D. , Qualman Stephen J. , Raney R. Beverly , Ruymann Frederick B. , Womer Richard B. , Meyer William H. , Link Michael P. , Crist William M. 
Published: November 2002

PURPOSE: To define the clinical characteristics of rhabdomyosarcoma (RMS) occurring in children from ethnic minorities and determine whether these children have benefited equally from advances in therapy. PATIENTS AND METHODS: This was a retrospective cohort analysis of children treated on the Intergroup Rhabdomyosarcoma Study Group protocols between 1984 and 1997. The clinical features and outcomes of 336 African-American children and 286 children from other ethnic minorities were compared with those of white children (n = 1,721). RESULTS: African-American, other ethnic group, and white children enjoyed similar 5-year failure-free survivals (FFS) of 61%, 61%, and 66%, respectively, P = .15. Compared with white children, nonwhite patients more often had (1) invasive, T2 tumors (P = .03); (2) stage 2 or 3 tumors (P = .003); (3) large tumors (more than 5 cm, P < .006); and/or (4) tumors with positive regional nodes (ie, N1, P = .002). Using Cox proportional hazards analysis, seven patient risk categories were defined with significant differences in outcome. This model was then used to search for other factors associated with FFS after adjusting for these risk categories. Only T stage and age remained associated with FFS (P = .001 and P < .001, respectively). After adjusting for T stage, risk category, and age, we explored the relationship of ethnic group to FFS and found that, compared with whites, the relative risk of failure was 1.14 for African-American patients and 1.2 for other ethnic minority patients, values that are not significantly different. CONCLUSION: Patients from ethnic minority groups more often have larger, invasive tumors with positive lymph nodes. Nevertheless, they have benefited as equally as white children from the dramatic progress in therapy of RMS.
Metalloproteinase inhibitors: biological actions and therapeutic opportunities
Authors: Baker Andrew H. , Edwards Dylan R. , Murphy Gillian 
Published: November 2002

Tissue inhibitors of metalloproteinases (TIMPs) are the major cellular inhibitors of the matrix metalloproteinase (MMP) sub-family, exhibiting varying efficacy against different members, as well as different tissue expression patterns and modes of regulation. Other proteins have modest inhibitory activity against some of the MMPs, including domains of netrins,the procollagen C-terminal proteinase enhancer (PCPE), the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), and tissue factor pathway inhibitor (TFPI-2), but their physiological significance is not at all clear.α2-Macroglobulin, thrombospondin-1 and thrombospondin-2 can bind to some MMPs and act as agents for their removal from the extracellular environment. In contrast, few effective inhibitors of other members of the metzincin family, the astacins or the distintegrin metalloproteinases, ADAMs have been identified.Many of these MMP inhibitors, including the TIMPs, possess other biological activities which may not be related to their inhibitory capacities. These need to be thoroughly characterized in order to allow informed development of MMP inhibitors as potential therapeutic agents. Over activity of MMPs has been implicated in many diseases, including those of the cardiovascular system,arthritis and cancer. The development of synthetic small molecule inhibitors has been actively pursued for some time, but the concept of the use of the natural inhibitors, such as the TIMPs, in gene based therapies is being assessed in animal models and should provide useful insights into the cell biology of degradative diseases.
Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin
Authors: McCaig Catherine , Perks Claire M. , Holly Jeff M. P. 
Published: November 2002

The insulin-like growth factor binding proteins (IGFBPs) have IGF-independent differential effects on cell function. We investigated whether they can affect integrin-receptor-mediated cell attachment to different extracellular matrix (ECM) components in Hs578T cells.Cell attachment to a general ECM gel was unaffected by IGFBP-1 and -6 but was significantly increased by IGFBP-4 and -5 and decreased by IGFBP-2 and -3. Similar results were obtained for attachment to laminin or collagen type IV. Attachment to fibronectin, however, was increased by IGFBP-3 and decreased by IGFBP-5. The actions of IGFBP-3 and -5 on cell attachment to ECM were lost in the presence of a soluble Arg-Gly-Asp (RGD)-containing fibronectin fragment. Thrombospondin reversed the actions of IGFBP-3 on cell attachment, but IGFBP-5 still increased cell attachment.On plastic, neither IGFBP-3 nor -5 alone affected cell viability; although ceramide-induced apoptosis was enhanced by IGFBP-3 but reduced by IGFBP-5. The presence of RGD reversed the action of IGFBP-5 on cell death but attenuated that of IGFBP-3. With cells grown on fibronectin, the action of IGFBP-3 was reversed, and it conferred cell survival, whereas the survival effect of IGFBP-5 was lost.In summary we have demonstrated that IGFBP-3 and -5 both have intrinsic effects on cell survival. In each case the presence of fibronectin or fibronectin fragments determines whether susceptibility to apoptosis is increased or decreased. These effects on cell survival are paralleled by acute effects on integrin receptor function; IGFBP-3 and -5 were able to either enhance or inhibit cell attachment in the presence of fibronectin. Cell survival is tightly controlled by cues from the ECM and from growth factors, particularly the IGFs. Our findings indicate that, in addition to being crucial modulators of IGF actions, the IGFBPs have direct actions on cell attachment and survival that are specific and dependent upon the matrix components present.
The role of CD34 expression and cellular fusion in the regeneration capacity of myogenic progenitor cells
Authors: Jankowski Ron J. , Deasy Bridget M. , Cao Baohong , Gates Charley , Huard Johnny 
Published: November 2002

Characterization of myogenic subpopulations has traditionally been performed independently of their functional performance following transplantation. Using the preplate technique, which separates cells based on their variable adhesion characteristics, we investigated the use of cell surface proteins to potentially identify progenitors with enhanced regeneration capabilities. Based on previous studies, we used cell sorting to investigate stem cell antigen-1 (Sca-1) and CD34 expression on myogenic populations with late adhesion characteristics. We compared the regeneration efficiency of these sorted progenitors, as well as those displaying early adhesion characteristics, by quantifying their ability to regenerate skeletal muscle and restore dystrophin following transplantation into allogenic dystrophic host muscle.Identification and utilization of late adhering populations based on CD34 expression led to differential regeneration, with CD34-positive populations exhibiting significant improvements in dystrophin restoration compared with both their CD34-negative counterparts and early adhering cell populations. Regenerative capacity was found to correspond to the level of myogenic commitment, defined by myogenic regulatory factor expression, and the rate and degree of induced cell differentiation and fusion. These results demonstrate the ability to separate definable subpopulations of myogenic progenitors based on CD34 expression and reveal the potential implications of defining myogenic cell behavioral and phenotypic characteristics in relation to their regenerative capacity in vivo.
Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells
Authors: Amasheh Salah , Meiri Noga , Gitter Alfred H. , Schöneberg Torsten , Mankertz Joachim , Schulzke Jörg D. , Fromm Michael 
Published: November 2002

Tight junctions seal the paracellular pathway of epithelia but, in leaky tissues, also exhibit specific permeability. In order to characterize the contribution of claudin-2 to barrier and permeability properties of the tight junction in detail, we studied two strains of Madin-Darby canine kidney cells(MDCK-C7 and MDCK-C11) with different tight junctional permeabilities.
Monolayers of C7 cells exhibited a high transepithelial resistance (&gt;1 kΩ cm2), compared with C11 cells (&lt;100 Ωcm2). Genuine expression of claudin-1 and claudin-2, but not of occludin or claudin-3, was reciprocal to transepithelial resistance. However,confocal microscopy revealed a marked subjunctional localization of claudin-1 in C11 cells, indicating that claudin-1 is not functionally related to the low tight junctional resistance of C11 cells.
Strain MDCK-C7, which endogenously does not express junctional claudin-2,was transfected with claudin-2 cDNA. In transfected cells, but not in vector controls, the protein was detected in colocalization with junctional occludin by means of immunohistochemical analyses. Overexpression of claudin-2 in the originally tight epithelium with claudin-2 cDNA resulted in a 5.6-fold higher paracellular conductivity and relative ion permeabilities of Na+≡1, K+=1.02, NMDG+=0.79,choline+=0.71, Cl-=0.12, Br-=0.10 (vector control, 1:1.04:0.95:0.94:0.85:0.83). By contrast, fluxes of (radioactively labeled) mannitol and lactulose and (fluorescence labeled) 4 kDa dextran were not changed. Hence, with regular Ringer's, Na+ conductivity was 0.2 mS cm-2 in vector controls and 1.7 mS cm-2 in claudin-2-transfected cells, while Cl- conductivity was 0.2 mS cm-2 in both cells. Thus, presence of junctional claudin-2 causes the formation of cation-selective channels sufficient to transform a `tight'tight junction into a leaky one.