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Biomedical subjects

A Latorre

Publications and source records attributed to A Latorre.

At least 19 recordsLinked to original sources

Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC). A phase II study of the GOIM (Gruppo Oncologico dell'Italia Meridionale).

BACKGROUND: Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. PATIENTS AND METHODS: Thirty-eight advanced breast cancer patients refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m(2) (days 1 + 8), and capecitabine 2000 mg/m(2) (days 2-7 and 9-16) every 3 weeks. RESULTS: A total of 228 courses were given with a mean of three cycles/patient (range 1-12). Five patients (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia grade 2-3 in seven patients (18.9%) and grade 4 in one patient (2.7%), anemia grade 1 in 11 patients (29.7%), grade 2-3 in five patients (13.5%), thrombocytopenia grade 1 in six patients (16.2%) and grade 3 in one patient (2.7%). Non-hematologic side-effects were: fatigue grade 1 in five patients (13.5%), hand-foot syndrome grade 1 in two patients (5.4%) and grade 2 in two patients (5.4%), nausea/vomiting grade 1 in two patients (5.4%), grade 2 in three patients (8.1%) and grade 3 in one patient (2.7%), constipation grade 1 in two patients (5.4%), peripheral neurotoxicity grade 1 in three patients (8.1%) and grade 2 in one patient (2.7%), gastric pain grade 1 in two patients (5.4%), stomatitis grade 1 in three patients (8.1%) and grade 2 in one patient (2.7%). Out of 38 patients assessable, we observed two (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD and nine (26.3%) PD. The median time to progression was 4.5 months (range 1-18 months), the median response duration was 7 months (range 2-18 months) and the median survival duration was 10 months (range 2-26+). CONCLUSIONS: The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination.

Administration, Oral↗

Anaerobic digestion of linear alkyl benzene sulfonates: biodegradation kinetics and metabolite analysis.

In the present work the effect of the alkyl chain length and the position of the sulfophenyl substituent of the linear alkylbenzene sulfonates (LAS) on their anaerobic biodegradability have been investigated. Degradation kinetics of the linear alkyl benzene sulfonates homologues, 2phiC10LAS, 2phiC12LAS and 2phiC14LAS, have been studied. It has been also investigated the effect of the isomer type on the degradation rate of the LAS molecule through the comparative study of the 2phiC10LAS and 5phiC10LAS isomers. Batch anaerobic biodegradation tests were performed using sludge from the anaerobic digester of a wastewater treatment plant as microorganisms source. Ultimate biodegradation was evaluated from the biogas production whereas primary biodegradation was determined by specific analysis of the surfactant. LAS homologues and isomers showed a negligible primary biodegradation under anaerobic conditions. Furthermore, analysis of sulfophenyl carboxilates (SPC) by LC-MS indicated a low and constant level of these LAS degradation metabolites over the test period. These data are consistent with a minimal transformation of the LAS parent molecule in the anaerobic digesters. On the other hand, the addition of the shortest alkyl chain length homologues, decyl and dodecylbenzene sulfonates, reduces the biogas production whereas the most hydrophobic homologue, the tetradecylbenzene sulfonate, enhances the biogas production. This LAS homologue seems to increase the availability of organic compounds sorbed on the anaerobic sludge promoting their biodegradation.

Adsorption↗

Determination of nonylphenol and octylphenol in paper by microwave-assisted extraction coupled to headspace solid-phase microextraction and gas chromatography-mass spectrometry.

A novel and simple method for the determination of active endocrine disrupter compounds (octylphenol OP, and nonylphenol NP) in paper using microwave-assisted extraction (MAE) and headspace solid-phase microextraction, coupled with gas chromatography-mass spectrometry has been developed. Parameters affecting the efficiency in the MAE process such as exposure time and extraction solvent were studied in order to determine operating conditions. The optimised method was linear over the range studied (1.25-125 microg kg(-1) for OP and 9.50-950 microg kg(-1) for NP) and showed good level of precision, with a RSD lower than 10% and detection limits at 0.10 and 4.56 microg kg(-1) for OP and NP, respectively. The results obtained from six different types of paper revealed the presence of the target compounds in all samples analysed, at levels ranging between 3 and 211 microg kg(-1).

Calibration↗

Chromosomal stasis versus plasmid plasticity in aphid endosymbiont Buchnera aphidicola.

The study of three genomes of the aphid endosymbiont Buchnera aphidicola has revealed an extraordinary stasis: conservation of gene order and genetic composition of the chromosome, while the chromosome size and number of genes has reduced. The reduction in genome size appears to be ongoing since some lineages we now know to have even smaller chromosomes than the first B. aphidicola analysed. The current sequencing by our group of one of these smaller genomes with an estimated size of 450 kb, and its comparison with the other three available genomes provide insights into the nature of processes involved in shrinkage. We discuss whether B. aphidicola might be driven to extinction and be replaced by secondary aphid endosymbionts. In some lineages, genes encoding key enzymes in the pathways leading to tryptophan and leucine biosynthesis (trpEG and leuABCD, respectively) are located on plasmids, rather than the main chromosome. In contrast to the stasis of the main chromosome, plasmid genes have frequently been transferred to the main chromosome and undergone other gene rearrangements. We propose a two-step scenario to explain these contrasting modes of evolution. Essential genes may have escaped regulation by moving to plasmids in a moving B. aphidicola ancestor. B. aphidicola became polyploidy at a given stage of its evolution and plasmid genes have been transferred to the main chromosome through several independent events.

Animals↗

Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer.

BACKGROUND: Several studies looked for tumor biomarkers predictive for paclitaxel sensitivity but till now no reliable biomarkers are available. The aim of this study was to verify the potential predictive value of beta-tubulin III and IV, vascular endothelial growth factor-receptor (VEGFR-1), HER2/neu and microvessel density (mVD), in a group of 70 patients with advanced breast cancer (ABC) treated with paclitaxel-based chemotherapy. PATIENTS AND METHODS: Immunohistochemical analysis (ICA) of HER2, VEGFR-1, mVd, beta-tubulin III and beta-tubulin IV expression were performed in a series of 72 advanced breast cancer. Furthermore apoptotic fraction with TUNEL analysis was evaluated. RESULTS: beta-tubulin III ICA expression was predictive of progression after chemotherapy. In fact only 2% of the patients with low beta-tubulin III expression progressed after paclitaxel chemotherapy vs 38% of those with high beta-tubulin III tumor expression (P=0.000; by chi(2)). This evidence was confirmed by a logistic regression analysis (OR 28.789; 95% CI 3.212-258,072; P=0.004). There was not a significant association between other biomarkers' characteristics and clinical response to chemotherapy. A Cox multivariate analysis, with overall survival as a dependent variable, showed that only HER2 expression was independently associated (OR 2.39; 95% CI 1.09-5.23; P=0.03) with overall survival. CONCLUSIONS: We suggest that class III beta-tubulin immunohistochemical expression analysis could be a potentially relevant tumor biomarker for paclitaxel resistance in advanced breast cancer patients.

Adult↗

Host-based divergence in populations of the pea aphid: insights from nuclear markers and the prevalence of facultative symbionts.

In North America, the pea aphid Acyrthosiphon pisum encompasses ecologically and genetically distinct host races that offer an ideal biological system for studies on sympatric speciation. In addition to its obligate symbiont Buchnera, pea aphids harbour several facultative and phylogenetically distant symbionts. We explored the relationships between host races of A. pisum and their symbiotic microbiota to gain insights into the historical process of ecological specialization and symbiotic acquisition in this aphid. We used allozyme and microsatellite markers to analyse the extent of genetic differentiation between populations of A. pisum on pea, alfalfa and clover in France. In parallel, we examined: (i) the distribution of four facultative symbionts; and (ii) the genetic variation in the Buchnera genome across host-associated populations of A. pisum. Our study clearly demonstrates that populations of A. pisum on pea, clover and alfalfa in France are genetically divergent, which indicates that they constitute distinct host races. We also found a very strong association between host races of A. pisum and their symbiotic microbiota. We stress the need for phylogeographic studies to shed light on the process of host-race formation and acquisition of facultative symbionts in A. pisum. We also question the effects of these symbionts on aphid host fitness, including their role in adaptation to a host plant.

Adaptation, Biological↗

Comparison of gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry for the determination of fatty and resin acids in paper mill process waters.

A comparative study of the performance of liquid chromatography (LC)-atmospheric pressure chemical ionisation (APCI)-mass spectrometry (MS) and gas chromatography (GC)-mass spectrometry techniques for the determination of resin and fatty acids from paper mill process waters was carried out. These compounds are responsible for the high toxicity of paper mill effluents and little research has been carried out regarding their analysis using mass spectrometric techniques. To prove the usability of GC and LC-MS, 16 treated and untreated water samples of recycle, kraft and pulp paper mills were analysed and good agreement was observed as regards to compounds detected and corresponding concentrations. This paper also reports the limits of detection, recoveries, reproducibility, linearity and precision using the two methods. GC-MS presented better selectivity and lower detection limits (below 0.2 microg/l), but derivatization of the extracts and the short life of derivatives (12-24 h) made the technique tedious and prone to high variations. Although LC-APCI-MS presented coelution of the non-aromatic resin acids, it also showed good sensitivity (limits of detection <3 microg/l) and permitted the detection of resin and fatty acids at microg/l level. In addition, since samples could be directly injected to the chromatographic system, LC-APCI-MS was proven as a powerful technique for quick and unequivocal quality control during papermaking.

Atmospheric Pressure↗

Phase I/II study of gemcitabine plus mitoxantrone as salvage chemotherapy in metastatic breast cancer.

The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline and/or taxanes, were treated with mitoxantrone 10 or 12 mg m(-2) intravenously on day 1 plus gemcitabine in escalating doses from 600 to 1200 mg m(-2) intravenously on days 1 and 8, every 3 weeks. In phase I, on 23 patients entered on study, dose-limiting toxicity occurred at the dosage of 1200 mg m(-2) gemcitabine and 10 mg m(-2) mitoxantrone, with three out of five patients developing grade 4 neutropenia. In phase II, with gemcitabine administered at 1000 mg m(-2) and mitoxantrone at 10 mg m(-2), 12 (30%) out of 40 assessable patients responded, even if no complete response was obtained. Moreover, stable disease was observed in eight (20%) patients. The median time to treatment failure was 22 weeks (range, 2-33), and median survival was 42 weeks (range, 2-92). Grade 3 and 4 neutropenia were observed in 12 (30%) and one (2.5%) cases respectively; grade 3 thrombocytopenia was observed in two patients (5%), grade 2 mucositis in two patients (5%), grade 3 anaemia in two patients (5%), grade 3 alopecia in one patient (2.5%) and asymptomatic cardiotoxicity in three patients (8%), respectively. In conclusion, the doses of 10 mg m(-2) (day 1) for mitoxantrone and 1000 mg m(-2) for gemcitabine (days 1-8) every 3 weeks resulted active and safe in MBC. Further investigations in less heavily pretreated patients are warranted.

Adult↗

Direct determination of resin and fatty acids in process waters of paper industries by liquid chromatography/mass spectrometry.

Liquid chromatography/mass spectrometry (LC/MS)-based methods were developed for the analysis of 10 resin acids and five fatty acids in process waters of paper industries. No fragmentation of target compounds was observed using atmospheric pressure chemical ionization (APCI) with negative ionization. The [M - H](-) ion permitted the individual quantification of fatty and aromatic resin acids, whereas the non-aromatic resin acids presented a single and common ion at m/z 301. Separation with two columns of different polarity permitted peak confirmation. The method that used a C(8) column with 2-propanol in the mobile phase allowed a certain separation and identification of the non-aromatic resin acids, whereas the method using a C(18) column provided detection limits 10-fold lower for fatty acids. Limits of detection were 0.10 ng for all compounds. Direct sample introduction was compared with liquid-liquid extraction, with similar recoveries (70-101%). Whereas slightly lower detection limits were obtained with liquid-liquid extraction, better reproducibility was observed for direct sample introduction. Resin and fatty acids were determined in process waters of several paper industries. Palmitic, dehydroabietic and non-aromatic resin acids were encountered in most water samples, at levels between 22 and 403 micro g l(-1). LC/MS with direct sample introduction was found to be a good alternative to traditional liquid-liquid extraction and gas chromatography for the analysis of such compounds since no derivatization was required and sample manipulation was minimal.

Calibration↗

Side-stepping secondary symbionts: widespread horizontal transfer across and beyond the Aphidoidea.

To elucidate the co-evolutionary relationships between phloem-feeding insects and their secondary, or facultative, bacterial symbionts, we explore the distributions of three such microbes--provisionally named the R-type (or PASS, or S-sym), T-type (or PABS), and U-type--across a number of aphid and psyllid hosts through the use of diagnostic molecular screening techniques and DNA sequencing. Although typically maternally transmitted, phylogenetic and pairwise divergence analyses reveal that these bacteria have been independently acquired by a variety of unrelated insect hosts, indicating that horizontal transfer has helped to shape their distributions. Based on the high genetic similarity between symbionts in different hosts, we argue that transfer events have occurred recently on an evolutionary timescale. In several instances, however, closely related symbionts associate with related hosts, suggesting that horizontal transfer between distant relatives may be rarer than transmission between close relatives. Our findings on the prevalence of these symbionts within many aphid taxa, along with published observations concerning their effects on host fitness, imply a significant role of facultative symbiosis in aphid ecology and evolution.

Animals↗

Determination of toxic compounds in paper-recycling process waters by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry.

Three analytical methods were developed for the determination of toxic compounds in recirculating waters of a paper-recycling industry. Three main groups of compounds were considered: (i) wood extractives originated from the raw material; (ii) biocides added during the production process and (iii) surfactants and other adjuvants present in the formulates of these biocides. Wood extractives considered in this study included fatty and resin acids. They were analysed by liquid-liquid extraction using methyl tert.-butyl ether, followed by gas chromatography-mass spectrometry for previous formation of the respective trimethylsilyl esters. Water samples were also extracted with Oasis HLB (copolymer [poly(divinylbenzene-co-N-vinylpyrrolidone]) solid-phase extraction cartridges of 60 mg and analysed by liquid chromatography-electrospray mass spectrometry for the determination of additives and biocides. Using these two approaches levels up to 15 mg/l for total resin and fatty acids, 5 mg/l for alkylbenzene sulfonates and 2-(thiocyanomethylthio)benzotiazol, 100 microg/l for bisphenol A and 2,2-dibromo-3-nitrilepropionamide, and 300 microg/l for nonylphenol ethoxycarboxylate were detected in process waters at different production treatment stages. These levels are of relevance since poor water quality affects the paper-recycling process, the primary water treatment process and eventually, the environmental water quality.

Chromatography, Liquid↗

Linkage disequilibria between mtDNA haplotypes and chromosomal arrangements in a natural population of Drosophila subobscura.

The association between mtDNA haplotypes and chromosomal arrangements in a natural population of Drosophila subobscura from Calvia (Balearic Islands, Spain) was studied in order to search for linkage disequilibria, in an attempt to explain the populational dynamics of the mtDNA haplotypes of this species in nature. The presence of Wolbachia was not detected. Two main haplotypes (I and II) were found, as well as a series of less common ones. The Tajima D-test seemed to indicate some kind of seasonal population bottleneck. An analysis of linkage disequilibrium and factorial analysis of correspondences detected an association between haplotype I and the J(ST) inversion and haplotype II and the J(1) inversion.

Animals↗

Epithelial ovarian cancer: second and third line chemotherapy (review).

Standard therapy for patients affected with advanced epithelial ovarian cancer is cytoreductive surgery followed by combination chemotherapy. With this treatment, most patients obtain clinical complete or partial response, nevertheless, relapse is common and salvage chemotherapy is often needed. The probability of response to second line chemotherapy following platinum-based treatments is usually related to the platinum-free interval, even if recent studies have reported some other clinical features as having prognostic value, such as tumour burden and histology. Salvage monochemotherapy is generally used, but when the platinum-free interval is longer than 24 months, re-treatment with platinum compounds and/or taxanes is indicated. Moreover, a number of new agents with demonstrated activity in ovarian cancer are currently available. Sequentially used in recurrent disease, these agents may improve survival and/or quality of life. Among these new drugs, the most promising are: topotecan, doxil, gemcitabine and platinum analogues such as oxaliplatin, nedaplatin, satraplatin, BBR3464 and ZD0473. However, the real aim of salvage chemotherapy in relapsed ovarian cancer still remains palliative care, because complete responses are very rarely reported and long lasting responses are very seldom observed.

Antineoplastic Agents↗

[Acquired and inherited hypercoagulability among patients with cerebral venous thrombosis].

BACKGROUND: Cerebral venous thrombosis (CVT) is considered to be a relative unusual pathology, probably underdiagnosed. Many acquired and inherited hypercoagulability states (HS) have been described as cause of CVT. OBJECTIVE: [corrected] We evaluated the incidence of acquired and inherited thrombophilic risk factors in a population of CVT patients. METHODS: Hypercoagulability studies were to carried out for patients suffering from radiologically confirmed CVT during a 3 year period (1998-2000). Prothrombin time, aPTT, protein C, protein S and antithrombin III activities, screening and confirmatory tests for lupus anticoagulant (LA), and activated protein C resistance (APCR) were tested. Genetic tests for G1691A factor V (Factor V Leiden), G20210A prothrombin and C677T methylentetrahidrofolate reductase (MTHFR) were performed. Computer database was used for descriptive statistics. RESULTS: 16 patients with CVT (M/F, 6/10) were screened for inherited and acquired coagulation disorders. Mean age of 23.66 years with standard desviation of 19.74 years. Two older patients had antecedents of thrombosis (ischemic stroke and deep-vein thrombosis in leg). We found 1 heterocygosis factor V Leiden associated to LA, 2 heterocygosis G20210A prothrombin (one associated to LA), 2 homocygosis C677T MTHFR, 1 hereditary antithrombin III deficiency and 4 LA. COMMENTS: Although this is a small series, we found a high incidence of hereditary (37.5%) and acquired (37.5%) thrombophilia in patients with CVT.

Adolescent↗

Molecular systematics of aphids and their primary endosymbionts.

Aphids constitute a monophyletic group within the order Homoptera (i.e., superfamily Aphidoidea). The Aphidoidea originated in the Jurassic about 150 my ago from some aphidiform ancestor whose origin can be traced back to about 250 my ago. They exhibit a mutualistic association with intracellular bacteria (Buchnera sp.) related to Escherichia coli. Buchnera is usually considered the aphids' primary endosymbiont. The association is obligate for both partners. The 16S rDNA-based phylogeny of Buchnera from four aphid families showed complete concordance with the morphology-based phylogeny of their aphid hosts, which pointed to a single original infection in a common ancestor of aphids some 100-250 my ago followed by cospeciation of aphids and Buchnera. This study concentrated on the molecular phylogeny of both the aphids and their primary endosymbionts of five aphid families including for the first time representatives of the family Lachnidae. We discuss results based on two Buchnera genes (16S rDNA and the beta subunit of the F-ATPase complex) and on one host mitochondrial gene (the subunit 6 of the F-ATPase complex). Although our data do not allow definitive evolutionary relationships to be established among the different aphid families, some traditionally accepted groupings are put into question from both bacterial and insect data. In particular, the Lachnidae and the Aphididae, which from morphological data are considered recently evolved sister groups, do not seem to be as closely related as is usually accepted. Finally, we discuss our results in the light of the proposed parallel evolution of aphids and their endosymbionts.

Animals↗

Taurine levels and localisation in the stratified squamous epithelia.

The content and distribution of the amino acid taurine in squamous epithelia were studied using high-performance liquid chromatography and immunohistochemical methods. Quantitative analysis demonstrated that taurine was highly concentrated in the epidermis (5.49 mumol/g fresh tissue in the hairless skin of the hind footpad of the rat), although the values in the isolated stratum corneum were extremely low (< 0.073 mumol/g in the horny layer of the same skin area). No other analysed amino acid (such as glutamate, glutamine, glycine or alanine) showed this specific pattern of distribution. The immunohistochemical study revealed that in the dog and rat epidermis, taurine was present in the keratinocytes of the granular and upper spinous layers. The basal layer, lower spinous layer and stratum corneum were immunonegative. A similar immunostaining pattern was found in the epithelia of the different organs studied: the mouth, tongue and oesophagus of the dog and rat, the rat forestomach and the rat corneal epithelium. Other cell types, such as sebaceous and muscle cells, were immunolabelled. The existence of a circulating pool of taurine in the epidermis (via taurine release from keratinocytes before they reach the horny layer and its uptake by nearby cells) and its possible roles in these cells are discussed.

Animals↗

Genome size reduction through multiple events of gene disintegration in Buchnera APS.

The evolution of the endosymbiont Buchnera during its adaptation to intracellular life involved a massive reduction in its genome. By comparing the orthologous genes of Buchnera, Escherichia coli and Vibrio cholerae, we show that the minimal genome size of Buchnera arose from multiple events of gene disintegration dispersed over the whole genome. The elimination of the genes was a continuous process that began with gene inactivation and progressed until the DNA corresponding to the pseudogenes were completely deleted.

Biological Evolution↗