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991.
Annunziato Mangiola Gina Lama Cecilia Giannitelli Pasquale De Bonis Carmelo Anile Libero Lauriola Giuseppe La Torre Giovanni Sabatino Giulio Maira Meena Jhanwar-Uniyal Gigliola Sica 《Clinical cancer research》2007,13(23):6970-6977
PURPOSE: It has been hypothesized that brain tumors are derived from stem cell or transiently dividing precursor transformation. Furthermore, c-Jun NH(2)-terminal kinases (JNKs) have been involved in gliomagenesis. This study analyzes stem cell marker nestin and JNK expression in glioblastoma multiforme (GBM) and peritumor tissue and assesses their possible prognostic implications. EXPERIMENTAL DESIGN: Nestin and both total JNK (tJNK) and phosphorylated JNK (pJNK) expression was investigated by immunohistochemistry in 20 GBMs. Samples were derived from tumors (first area), from tissues at a distance <1 cm (second area), and between 1 and 3.5 cm (third area) from the macroscopic tumor border. The relationships between patients' age, Karnofsky performance status, gender, protein expression, and survival were analyzed. RESULTS: Nestin cytoplasmic immunoreactivity was observed in the majority of cells in tumor but infrequently in peritumor areas. tJNK, observed in the nucleus and cytoplasm, was widely expressed in the three areas; pJNK, mostly located in the nuclei, was found in a variable percentage of cells in the tumor and peritumor tissue. Nestin and JNK expression in peritumor areas was independent of the presence of neoplastic cells. Univariate analysis indicated that survival was longer (19 versus 12 months; P = 0.01) for patients whose pJNK/nestin and (pJNK/tJNK)/nestin ratios in the second area were > or =2.619 and > or =0.026, respectively. The same variables showed an independent prognostic value in multivariate analysis. CONCLUSIONS: Nestin and JNK expression indicates that peritumor tissue, independently of the presence of neoplastic cells, may present signs of transformation. Moreover, pJNK/nestin and (pJNK/tJNK)/nestin ratios in that tissue seem to have some prognostic implications in GBM patients. 相似文献
992.
Carlo Barone Michele Basso Giovanni Schinzari Carmelo Pozzo Nunziatina Trigila Ettore D'Argento Michela Quirino Antonio Astone Alessandra Cassano 《Gastric cancer》2007,10(2):104-111
Background In advanced gastric cancer few data are available on the efficacy or safety of new drug combination regimens after progression
following first-line chemotherapy.
Methods Patients with histologically confirmed advanced gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status
(PS) less than 2, progressing after first-line chemotherapy, were eligible. Patients were treated with docetaxel 75 mg/m2 on day 1 and oxaliplatin 80 mg/m2 on day 2, every 3 weeks, until progression or unacceptable toxicity.
Results Between May 2002 and April 2005, 38 patients were enrolled. Men accounted for 73.7% of the patients and the median age was
59 years. The primary tumor was not resected in 47.4% of the patients; the peritoneum was the most frequent metastatic site
(60.5%). The first-line treatment was cisplatin, epirubicin, and infusional 5-fluorouracil (ECF) in 81.5% of the patients
and cisplatin and infusional 5-fluorouracil (CF) in 15.7%. The median number of cycles was 4.3. The treatment was well tolerated,
with no toxic deaths. National Cancer Institute (NCI) grade III-IV neutropenia was frequent (26.3%), but no febrile neutropenia
was reported. Severe asthenia (15.7%) and severe nausea (15.7%) required dose reductions in 2 patients and treatment discontinuation
in another. The overall response rate was 10.5%, and 18 patients (47.3%) experienced disease stabilization (7 of them with
significant clinical benefit). Median time to progression was 4.0 months (range, 2–8 months) and median overall survival was
8.1 months (range, 3–26 months). Thirteen patients (34.2%) also received third-line chemotherapy, with an irinotecan-containing
regimen, and their median overall survival was higher than that of the other patients (16.3 vs 6.0 months)
Conclusion The combination of oxaliplatin and docetaxel shows only marginal activity as second-line treatment, but it has a good tolerability
profile. This suggests that there is room for optimizing the schedule as well as for planning sequential treatments in gastric
cancer. 相似文献
993.
Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. 总被引:4,自引:0,他引:4
Peng Hou Dingxie Liu Yuan Shan Shuiying Hu Kimberley Studeman Stephen Condouris Yangang Wang Ariel Trink Adel K El-Naggar Giovanni Tallini Vasily Vasko Mingzhao Xing 《Clinical cancer research》2007,13(4):1161-1170
PURPOSE: To investigate the overall occurrence and relationship of genetic alterations in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in thyroid tumors and explore the scope of this pathway as a therapeutic target for thyroid cancer. EXPERIMENTAL DESIGN: We examined collectively the major genetic alterations and their relationship in this pathway, including PIK3CA copy number gain and mutation, Ras mutation, and PTEN mutation, in a large series of primary thyroid tumors. RESULTS: Occurrence of any of these genetic alterations was found in 25 of 81 (31%) benign thyroid adenoma (BTA), 47 of 86 (55%) follicular thyroid cancer (FTC), 21 of 86 (24%) papillary thyroid cancer (PTC), and 29 of 50 (58%) anaplastic thyroid cancer (ATC), with FTC and ATC most frequently harboring these genetic alterations. PIK3CA copy gain was associated with increased PIK3CA protein expression. A mutual exclusivity among these genetic alterations was seen in BTA, FTC, and PTC, suggesting an independent role of each of them through the PI3K/Akt pathway in the tumorigenesis of the differentiated thyroid tumors. However, coexistence of these genetic alterations was increasingly seen with progression from differentiated tumor to undifferentiated ATC. Their coexistence with BRAF mutation was also frequent in PTC and ATC. CONCLUSIONS: The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate. Progression of PTC to ATC may be facilitated by coexistence of PI3K/Akt pathway-related genetic alterations and BRAF mutation. The PI3K/Akt pathway may thus be a major therapeutic target in thyroid cancers. 相似文献
994.
Omar S Punjabi Harry W Flynn John E Legarreta Giovanni Gregori Robert W Knighton Carmen A Puliafito 《Ophthalmic surgery, lasers & imaging》2007,38(4):330-332
An observational case series using an 8-microm axial resolution prototype spectral domain optical coherence tomography (OCT) system was performed in two patients with idiopathic macular holes. Spontaneous closure and visual acuity improvement occurred in both patients. Useful information about morphology and vitreoretinal relationship of the holes was provided by spectral domain OCT. 相似文献
995.
Giulia Bonacucina Marco Cespi Monica Misici-Falzi Giovanni F Palmieri 《European journal of pharmaceutics and biopharmaceutics》2007,67(1):277-283
The aim of this work was to verify how and to what extent rheological tests, carried out under dynamic (Heckel) and static (creep, stress/strain) porosity conditions, may serve as a valuable complement to the classic Heckel tests in the characterization of viscoelastic and densification properties of solid materials for pharmaceutical use. Six different modified (pregelatinized) starches were compressed in a rotary tablet machine equipped to measure force and punch displacement. Tablets were obtained using flat-faced 6mm diameter punches at different compression pressures. Compression cycles performed at the maximal pressure of 200MPa were used to build the Heckel plots. Ejected tablets at the 10%, 20%, 30%, and 40% porosity levels were used for the stress/strain and creep tests. Parameters obtained with both types of tests were consistent with each other. In particular, among the six starches, lower viscosity values corresponded to lower P(Y) values, and lower elastic modulus values corresponded to lower elastic recovery of the tablet. Mechanical properties of materials can be better characterized if viscoelastic tests performed under dynamic porosity conditions (Heckel analysis) are supported by classical viscoelastic tests carried out under conditions of static porosity. 相似文献
996.
997.
Alessio Squassina Donatella Congiu Francesca Manconi Mirko Manchia Caterina Chillotti Simona Lampus Giovanni Severino Maria Del Zompo 《Pharmacological research》2008,57(5):369-373
A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling. PDLIM5 (PDZ and LIM domain 5; LIM) is an adaptor protein that selectively binds the isozyme PKC(epsilon) to N-type Ca(2+) channels in neurons. We tested for an association between three single nucleotide polymorphisms (SNPs) at the PDLIM5 gene and lithium prophylaxis in a Sardinian sample comprised of 155 bipolar patients treated with lithium. In order to evaluate whether PDLIM5 expression interacts with lithium response, we carried out gene expression analysis in lymphoblastoid cells of 30 bipolar patients. No association was shown between PDLIM5 polymorphisms and lithium response. When PDLIM5 expression was evaluated, no significant differences were detected between Full Responders to lithium (total score>or=7) and other patients (total score相似文献
998.
A paclitaxel-hyaluronan bioconjugate targeting ovarian cancer affords a potent in vivo therapeutic activity. 总被引:1,自引:0,他引:1
Alessandra Banzato Sara Bobisse Maria Rondina Davide Renier Fabio Bettella Giovanni Esposito Luigi Quintieri Laura Meléndez-Alafort Ulderico Mazzi Paola Zanovello Antonio Rosato 《Clinical cancer research》2008,14(11):3598-3606
PURPOSE: This study was designed to evaluate the pharmacologic and biological properties of a paclitaxel-hyaluronan bioconjugate (ONCOFID-P) against IGROV-1 and OVCAR-3 human ovarian cancer xenografts following i.p. administration. EXPERIMENTAL DESIGN: In vitro tumor sensitivity to ONCOFID-P was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas bioconjugate interaction with cells was studied cytofluorimetrically and by confocal microscopy. In vivo toxicity was assessed by a single-dose maximum-tolerated dose, peripheral blood cell count determination and by histologic analysis. Biodistribution of the compound was evaluated with a small animal-dedicated scintigraphy gamma camera following injection of 99mTc-labeled ONCOFID-P. Pharmacokinetic analysis was also carried out. Female severe combined immunodeficiency mice implanted with ovarian cancer cells underwent treatment with ONCOFID-P or free paclitaxel starting from day 7 or 14 after tumor injection, and survivals were compared. RESULTS: ONCOFID-P interacted with CD44, entered cells through a receptor-mediated mechanism, and exerted a concentration-dependent inhibitory effect against tumor cell growth. After i.p. administration, the bioconjugate distributed quite uniformly within the peritoneal cavity, was well-tolerated, and was not associated with local histologic toxicity. Pharmacokinetic studies revealed that blood levels of bioconjugate-derived paclitaxel were much higher and persisted longer than those obtained with the unconjugated free drug. Intraperitoneal treatment of tumor-bearing mice with the bioconjugate revealed that ONCOFID-P exerted a relevant increase in therapeutic activity compared with free drug. CONCLUSIONS: ONCOFID-P significantly improved results obtained with conventional paclitaxel, in terms of in vivo tolerability and therapeutic efficacy; these data strongly support its development for locoregional treatment of ovarian cancer. 相似文献
999.
In vivo analysis of the gene expression profiles of cancer cells before and after treatment in patients may define mechanisms of sensitivity and resistance to specific drugs and ultimately allow for the selection of optimal individualized therapy to improve outcome in cancer. 相似文献
1000.
Francesco Legge Marco Petrillo Vincenzo Adamo Salvatore Pisconti Giovanni Scambia Gabriella Ferrandina 《BMC cancer》2008,8(1):367