bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of the Efficacy and Safety of Cisplatin-Epinephrine Injectable Gel Administered to Patients With Unresectable Hepatocellular Carcinoma
Authors: Leung T.W.T. , Yu S. , Johnson P.J. , Geschwind J. , Vogl T.J. , Engelmann K. , Gores G.J. , Giovannini M. , O’Grady J. , Heneghan M. , Stewart M. , Orenberg E.K. , Thuluvath P.J. 
Published: February 2003

Purpose: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). Patients and Methods: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured ≤ 7 cm, total tumor volume ≤ 200 cm3). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. Results: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. Conclusion: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.
Effect of Endothelin-A Receptor Blockade With Atrasentan on Tumor Progression in Men With Hormone-Refractory Prostate Cancer: A Randomized, Phase II, Placebo-Controlled Trial
Authors: Carducci Michael A. , Padley Robert J. , Breul Jurgen , Vogelzang Nicholas J. , Zonnenberg Bernard A. , Daliani Danai D. , Schulman Claude C. , Nabulsi Azmi A. , Humerickhouse Rod A. , Weinberg Mark A. , Schmitt Jennifer L. , Nelson Joel B. 
Published: February 2003

Purpose: To evaluate the efficacy and safety of atrasentan (ABT-627), an endothelin-A receptor antagonist, in the treatment of asymptomatic, hormone-refractory prostatic adenocarcinoma. Patients and Methods: A double-blind, randomized, placebo-controlled clinical trial of hormone-refractory prostate cancer (HRPCa) patients was conducted in the United States and Europe. Two hundred eighty-eight asymptomatic patients with HRPCa and evidence of metastatic disease were randomly assigned to one of three study groups receiving a once-daily oral dose of placebo, 2.5 mg atrasentan, or 10 mg atrasentan, respectively. Primary end point was time to progression; secondary end points included time to prostate-specific antigen (PSA) progression, bone scan changes, and changes in bone and tumor markers. Results: The three treatment groups were similar in all baseline characteristics. Median time to progression in intent-to-treat (ITT) patients (n = 288) was longer in the 10-mg atrasentan group compared with the placebo group: 183 v 137 days, respectively; (P = .13). Median time to progression in evaluable patients (n = 244) was significantly prolonged, from 129 days (placebo group) to 196 days (10-mg atrasentan group; P = .021). For both ITT and evaluable populations in the 10-mg atrasentan group, median time to PSA progression was twice that of the placebo group (155 v 71 days; P = .002). Patients who received placebo continued to have significant increases from baseline in serum (lactate dehydrogenase [LDH]), a marker of disease burden; elevations in LDH were uniformly attenuated by atrasentan in the ITT population. Headache, peripheral edema, and rhinitis were primary side effects, typically of mild to moderate severity. Quality of life was not adversely affected by atrasentan. Conclusion: Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa.
Radical Cystectomy for Bladder Cancer Today—A Homogeneous Series Without Neoadjuvant Therapy
Authors: Madersbacher Stephan , Hochreiter Werner , Burkhard Fiona , Thalmann George N. , Danuser Hansjörg , Markwalder Regula , Studer Urs E. 
Published: February 2003

Purpose: To investigate the effect of pelvic lymph node dissection and radical cystectomy for transitional cell cancer of the bladder on recurrence-free and overall survival, pelvic recurrences, and metastatic patterns in a homogeneous group. Patients and Methods: A consecutive series of patients undergoing pelvic lymphadenectomy and radical cystectomy between 1985 and 2000 was analyzed. All patients were staged N0, M0 preoperatively, and no patient received neoadjuvant radio/chemotherapy. Pathologic characteristics based on the 1997 tumor-node-metastasis system, recurrence-free/overall survival, and metastatic patterns were determined. Results: Five hundred seven patients (age 66 ± 12 years) with a mean follow-up time of 45 months (range, 0.1 to 176 months) were analyzed. Five-year recurrence-free and overall survival were, respectively, 73% and 62% for patients with organ-confined, lymph node-negative tumors (n = 217; ≤ pT2, pN0) and 56% and 49% for non-organ-confined, lymph node-negative tumors (n = 166; > pT2, pN0). Positive lymph nodes were found in 124 (24%) patients who had a 5-year recurrence-free (33%) or overall (26%) survival. Isolated local recurrences were observed in 3% of patients with organ-confined tumors (≤ pT2, pN0), 11% with non-organ-confined tumors (> pT2, pN0), and 13% with positive lymph nodes (any pT, pN+). Distant metastases developed in 25% of patients with organ-confined tumors, 37% with non-organ-confined tumors, and 51% with positive lymph nodes. Conclusion: Despite negative preoperative staging, pelvic lymphadenectomy and cystectomy for bladder cancer reveal a high percentage of unsuspected nodal metastases (24%) that have a 25% chance for long-term survival. This procedure also ensures a low pelvic recurrence rate even in lymph node-positive patients, and patients with locally advanced cancer have a 56% probability of 5-year recurrence-free survival.
Dysadherin Overexpression in Pancreatic Ductal Adenocarcinoma Reflects Tumor Aggressiveness: Relationship to E-Cadherin Expression
Authors: Shimamura Takeshi , Sakamoto Michiie , Ino Yoshinori , Sato Yasuto , Shimada Kazuaki , Kosuge Tomoo , Sekihara Hisahiko , Hirohashi Setsuo 
Published: February 2003

Purpose: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, we reported the cloning and characterization of dysadherin and showed that it downregulated E-cadherin and promoted metastasis. The aim of this study was to investigate the clinical significance of dysadherin expression and the relationship between dysadherin expression and E-cadherin expression in pancreatic ductal adenocarcinoma. Patients and Methods: We examined dysadherin and E-cadherin expression in 125 surgically resected pancreatic ductal adenocarcinoma patients using immunohistochemistry. Results: Dysadherin was expressed at the cell membrane of cancer cells, but not in nontumor duct and acinar cells. Its expression was stronger in infiltrative and poorly differentiated nests compared with well-differentiated nests. Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. Increased dysadherin expression was significantly correlated with distant metastasis (P = .047), high tumor grade (P = .006), positive tumor margins (P = .024), and infiltrative type of growth pattern (P = .014). A survival advantage was observed in patients with 0% to 20% dysadherin-positive cells compared with patients with 51% to 100% dysadherin-positive cells, independent of tumor-node-metastasis classification, and World Health Organization tumor grade (P = .019). A combination of increased dysadherin expression and reduced E-cadherin expression (< 90%) further worsened the prognosis. Conclusion: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin.
Intravesical Gemcitabine Therapy for Superficial Transitional Cell Carcinoma of the Bladder: A Phase I and Pharmacokinetic Study
Authors: Laufer Menachem , Ramalingam Sakkaraiappan , Schoenberg Mark P. , Haisfield-Wolf Mary Ellen , Zuhowski Eleanor G. , Trueheart Irene N. , Eisenberger Mario A. , Nativ Ofer , Egorin Merrill J. 
Published: February 2003

Purpose: To determine maximum-tolerated dose, toxicities, and pharmacokinetics associated with weekly intravesical gemcitabine therapy in patients with superficial bladder cancer. Patients and Methods: Fifteen patients with recurrent superficial transitional cell bladder carcinoma who experienced prior intravesical therapy failure were studied. Two to 4 weeks after complete transurethral resection, gemcitabine was administered intravesically, once weekly for 6 consecutive weeks. Dwell time was 2 hours. Pharmacokinetics of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine (dFdU), were studied in plasma and urine. Cystoscopy was repeated 6 weeks after therapy. Results: Three-patient cohorts were enrolled sequentially at doses of 500, 1,000, and 1,500 mg in 100 mL 0.9% NaCl. Two patients received 2,000 mg in 100 mL. An additional four patients received 2,000 mg in 50 mL. No grade 4 toxicity or clinically relevant myelosuppression was noted. Nine of 13 evaluable patients were recurrence-free at 12 weeks. Low concentrations of gemcitabine (≤ 1 μg/mL) were present transiently in plasma of all patients receiving 2,000 mg in 50 mL. Gemcitabine was undetectable in plasma of other patients. dFdU was undetectable in plasma of patients receiving less than 1,500 mg. At doses ≥ 1,500 mg, dFdU concentrations increased until 90 to 120 minutes and then declined little, if any. Plasma dFdU concentrations implied absorption of 0.5% to 5.5% of instilled dose. Between 61% and 100% of the gemcitabine dose was accounted for in voided urine. No dFdU was measured in voided urine. Conclusion: Intravesical gemcitabine, at doses up to 2 g/wk, is well tolerated, is associated with minimal systemic absorption, and has promising efficacy in treatment of superficial bladder cancer.
Alkylation and Acetal Formation Using Supercritical Alcohol without Catalyst
Authors: Horikawa Yoshiteru , Uchino Yuki , Sako Takeshi 
Published: February 2003

Abstract
The aromatic ring alkylation of phenols, N-alkylation of aniline, O-alkylation of phenols and acetal formation from acetaldehyde or acetone were examined using supercritical (SC) alcohol without any catalyst. Highly selective syntheses of monoalkylated compounds were achieved for the aromatic ring alkylation and N-alkylation. The O-alkylation proceeded more preferentially than the aromatic ring alkylation for phenols which have a deactivating group. The acetal formation went on in more than 96% selectivity.
Enantioselective Photopinacolization of Benzophenone and Benzhydrol Intercalated in Mg–Al LDH Interlayers
Authors: Shichi Tetsuya , Minamikawa Yukiko , Yasuda Naoto , Yamada Naoya , Okamoto Yoshio , Takagi Katsuhiko 
Published: February 2003

Abstract
A novel enantioselective photochemical pinacolization utilizing the interlayer spaces of layered double hydroxide (LDH) was investigated. UV irradiation of (+)-4-(α-hydroxy-α-phenyl)methylbenzoate [benzhydrol-4-carboxylate] ions (d-BHA) with 4-benzoylbenzoate ions (BBA) gave rise to the formation of (−)-1,2-bis(4-carboxyphenyl)-1,2-bisphenyl-1,2-ethanediol (l-benzopinacol) in the LDH interlayers. Similarly, l-BHA reacts with BBA to give d-benzopinacol in the LDH. A maximum optical yield of over 60%ee was observed at the initial reaction stage.
Polarizing microscope study of a contractile nanofilament system: the Acantharian myoneme
Authors: Febvre Jean , Febvre‐Chevalier Colette , Sato Hidemi 
Published: February 2003

Summary—Birefringence changes have been studied during the contraction—relaxation cycle of the myonemes (contractile organelles consisting of a bundle of nonactin filaments) in Acantharians (Protista, Actinopoda). Myonemes can either contract rapidly or undulate slowly between their anchorage points. In thin sections they appear as a large cross‐striated bundle with long clear zones (LZs) and thin transversal dense bands (TBs). The filaments (2–4 nm in diameter) are twisted in pairs in elementary microstrands. The spacing of the LZ depends on the extent of contraction [16]. A negative birefringence has been seen in vivo and in vitro. In vivo, retardation varied with the extent of relaxation of the myoneme (2.5 nm−4.4 nm). When the myoneme was tightened, it appeared to be homogeneously dark or bright in contrast depending on the orientation for the vibrating plane of polarized light. When it was partially relaxed and moved slowly, a series of birefringent bands, 0.8–2.8 μm thick, could be seen. They propagated at the same speed (about 2 μm·s−1) by successive trains, either forward or backward. Each of these birefringent bands may correspond to 4–13 contracted LZs. It is suggested that the negative birefringence of the myoneme is mainly caused by the orientation of the filaments forming the microstrands. Our results strongly suggest that the orientation of the myoneme filaments is altered during the movement and that the orientation of the filaments in the negative bands is caused by perpendicular orientation compared to the other parts of the myoneme. These observations support our previous hypothesis in which we postulated that the length of the myoneme varies in relation to the pitch of the elementary microstrands.
Membrane control of ciliary movement in ciliates
Authors: Andrivon Claude 
Published: February 2003

Summary— Ciliary movement is generated in the axoneme by the unidirectional sliding of the outer doublets of microtubules produced by the adenosine triphosphate (ATP)‐energized dynein arms. It is composed of an effective stroke phase and a passive recovery stroke phase. Two parameters are modulated to determine the swimming characteristics of the cell (speed and direction): (i) beat frequency; (ii) direction of the effective stroke.They are linked to the internal Ca++ level and to the membrane potential. The membrane governs the internal Ca++ level by regulating Ca++ influx and efflux. It contains voltage‐sensitive Ca++ channels through which is passive Ca++ influx, driven by the electrochemical gradient, occurs during step depolarization. The rise of the Ca++ level, up to 6.10−7M triggers ciliary reversal and enhances beat frequency. Ca++ is extruded from cilia by active transport. Ca++ also activities a multistep enzymatic process, the first component of which is a membrane calmodulin‐dependent guanylate cyclase. cGMP interacts with Ca++ to modulate the parameters of the ciliary beat. The phosphorylation‐ dephosphorylation cycle of axoneme and membrane proteins seems to play a major role in controlling ciliary movement.Hyperpolarization of the membrane enhances beat frequency by an unknown mechanism. It could be a modification of the ratio of axonemal bound Ca++ and Mg++, or activation by cyclic adenosine monophosphate (cAMP) produced by a membrane adenylate cyclase.The ciliary membrane behaves as a receptor able to detect modifications of external parameters, and as a transductor transmitting the detected signal by second or third messengers toward the interior of the cilia. These messengers, acting at different levels, modulat the parameters of the mechanism that generates ciliary movement.
Development and functions of the cytoskeleton during ciliogenesis in metazoa
Authors: Lemullois Michel , Boisvieux‐Ulrich Emmanuelle , Laine Marie‐Christine , Chailley Bernadette , Sandoz Daniel 
Published: February 2003

Summary— The different steps of ciliogenesis occurring in quail oviduct were compared to the ciliogenesis pattern described in other metazoan species.Centrioles are generated according to pathways that are found within the same cell: the centriolar and the acentriolar pathways. In the acentriolar pathway, centrioles are generated in the Golgi area, without contact with the preexisting centrioles of the centrosomes, and they migrate toward the apical membrane. The control of this polarized migration was studied by means of several drugs (colchicine, nocodazol, taxol, cytochalasin D, benzodiazepines) and immunocytochemistry.It was suggested that an actin‐myosin system was involved in the migration of centrioles, whereas labile microtubules were not necessary.Basal bodies must dock with plasma membrane or cytoplasmic vesicles for the initiation of axonemal microtubule polymerization. This signal is necessary even in the presence of taxol.
ULTRASTRUCTURAL LOCALIZATION OF ARGYROPHILIC PROTEINS IN NUCLEOLI OF ZEA MAYS BY TWO SILVER STAINING TECHNIQUES
Authors: MOTTE Patrick , MOSEN Henri , BRONCHART Raymond , DELTOUR Roger 
Published: February 2003

Summry—Ag staining was applied on interphasic nucleoli of Zea mays root cells 120h after germination. We applied the two‐step Ag‐NOR staining technique to small root fragments and the one‐step technique to sections of Lowicryl‐embedded tissue. The small‐sized silver grains were mainly located in the dense fibrillar component (DFC). The unstained fibrillar centers (FCs) differed in their proteinic contents from the NOR (which is positively silver stained) and were not the interphasic NOR counterpart.
EXPRESSION OF THE c‐fos PROTO‐ONCOGENE IN BONE, CARTILAGE AND TOOTH FORMING TISSUES DURING MOUSE DEVELOPMENT
Authors: CAUBET Jean‐François , BERNAUDIN Jean‐François 
Published: February 2003

Summry—The c‐fos proto‐oncogene is the cellular homologue of v‐fos identified as the bone transforming gene of the FBJ and the FBR murine osteosarcoma viruses. We show here, using a sensitive in situ hybridization method, that the c‐fos proto‐oncogene is expressed in the cartilage, bone and tooth forming tissues during mouse development. This result suggests that the tumors observed after infection by the FBJ viral complex and c‐fos overexpression in transgenic mice occur in those tissues in which c‐fos is expressed during development.
The effect of anthropogenic habitat usage on the social behaviour of a vulnerable species, Cyclura nubila
Authors: Lacy Kathryn E. , Martins Emília P. 
Published: February 2003

AbstractWith the increasing human population world‐wide, animals and humans are sharing more habitat. In this study, we consider the consequences of this habitat usage overlap on the behaviour patterns and social structure of a threatened species. Specifically, we used focal animal samples to collect data on the Cuban rock iguana, Cyclura nubila, in six field sites. Three of these sites are subject to considerable anthropogenic habitat usage, whereas three are in relatively low anthropogenic usage areas. Individuals in high anthropogenic usage sites were more closely assembled, with more males and females sharing a smaller amount of space. These animals exhibited even more aggressive behaviour and social interactions than expected when taking into account the larger number of possible interactants. High anthropogenic usage sites also had more male–male interactions and fewer males interacting with females. We suggest that social and mating system changes have occurred. Ramifications of these recent changes in the behavioural repertoires on the long‐term survival of the species are discussed.
Long‐distance wolf recolonization of France and Switzerland inferred from non‐invasive genetic sampling over a period of 10 years
Authors: Valière Nathaniel , Fumagalli Luca , Gielly Ludovic , Miquel Christian , Lequette Benoît , Poulle Marie‐Lazarine , Weber Jean‐Marc , Arlettaz Raphaël , Taberlet Pierre 
Published: February 2003

AbstractIn the early 1900s, the wolf (Canis lupus) was extirpated from France and Switzerland. There is growing evidence that the species is presently recolonizing these countries in the western Alps. By sequencing the mitochondrial DNA (mtDNA) control region of various samples mainly collected in the field (scats, hairs, regurgitates, blood or tissue; n= 292), we could (1) develop a non‐invasive method enabling the unambiguous attribution of these samples to wolf, fox (Vulpes vulpes) or dog (Canis familiaris), among others; (2) demonstrate that Italian, French and Swiss wolves share the same mtDNA haplotype, a haplotype that has never been found in any other wolf population world‐wide. Combined together, field and genetic data collected over 10 years corroborate the scenario of a natural expansion of wolves from the Italian source population. Furthermore, such a genetic approach is of conservation significance, since it has important consequences for management decisions. This first long‐term report using non‐invasive sampling demonstrates that long‐distance dispersers are common, supporting the hypothesis that individuals may often attempt to colonize far from their native pack, even in the absence of suitable corridors across habitats characterized by intense human activities.
In Plants, 3-O-Methylglucose Is Phosphorylated by Hexokinase But Not Perceived as a Sugar
Authors: Cortès Sandra , Gromova Marina , Evrard Adeline , Roby Claude , Heyraud Alain , Rolin Dominique B. , Raymond Philippe , Brouquisse Renaud M. 
Published: February 2003

Abstract
In plants, sugars are the main respiratory substrates and important signaling molecules in the regulation of carbon metabolism. Sugar signaling studies suggested that sugar sensing involves several key components, among them hexokinase (HXK). Although the sensing mechanism of HXK is unknown, several experiments support the hypothesis that hexose phosphorylation is a determining factor. Glucose (Glc) analogs transported into cells but not phosphorylated are frequently used to test this hypothesis, among them 3-O-methyl-Glc (3-OMG). The aim of the present work was to investigate the effects and fate of 3-OMG in heterotrophic plant cells. Measurements of respiration rates, protein and metabolite contents, and protease activities and amounts showed that 3-OMG is not a respiratory substrate and does not contribute to biosynthesis. Proteolysis and lipolysis are induced in 3-OMG-fed maize (Zea mays L. cv DEA) roots in the same way as in sugar-starved organs. However, contrary to the generally accepted idea, phosphorous and carbon nuclear magnetic resonance experiments and enzymatic assays prove that 3-OMG is phosphorylated to 3-OMG-6-phosphate, which accumulates in the cells. Insofar as plant HXK is involved in sugar sensing, these findings are discussed on the basis of the kinetic properties because the catalytic efficiency of HXK isolated from maize root tips is five orders of magnitude lower for 3-OMG than for Glc and Man.