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1.
Sci Rep ; 11(1): 4274, 2021 02 19.
Article in English | MEDLINE | ID: mdl-33608590

ABSTRACT

Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1-2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Estrogen Receptor Antagonists/therapeutic use , Fulvestrant/therapeutic use , Postmenopause/metabolism , Receptors, Estrogen/metabolism , Aged , Antineoplastic Agents, Hormonal/pharmacology , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/etiology , Estrogen Receptor Antagonists/pharmacology , Female , Fulvestrant/pharmacology , Humans , Middle Aged , Neoplasm Staging , Prognosis , Receptors, Estrogen/antagonists & inhibitors , Retrospective Studies , Treatment Outcome
2.
J Neuroimmune Pharmacol ; 16(4): 818-834, 2021 12.
Article in English | MEDLINE | ID: mdl-33502706

ABSTRACT

Inflammatory pain associates with spinal glial activation and central sensitization. Systemic administration of IMT504, a non-CpG oligodeoxynucleotide originally designed as an immunomodulator, exerts remarkable anti-allodynic effects in rats with complete Freund´s adjuvant (CFA)-induced hindpaw inflammation. However, the anti-nociceptive mechanisms of IMT504 remain unknown. Here we evaluated whether IMT504 blocks inflammatory pain-like behavior by modulation of spinal glia and central sensitization. The study was performed in Sprague Dawley rats with intraplantar CFA, and a single lumbosacral intrathecal (i.t.) administration of IMT504 or vehicle was chosen to address if changes in glial activation and spinal sensitization relate to the pain-like behavior reducing effects of the ODN. Naïve rats were also included. Von Frey and Randall-Selitto tests, respectively, exposed significant reductions in allodynia and mechanical hypersensitivity, lasting at least 24 h after i.t. IMT504. Analysis of electromyographic responses to electrical stimulation of C fibers showed progressive reductions in wind-up responses. Accordingly, IMT504 significantly downregulated spinal glial activation, as shown by reductions in the protein expression of glial fibrillary acidic protein, CD11b/c, Toll-like receptor 4 (TLR4) and the phosphorylated p65 subunit of NFκB, evaluated by immunohistochemistry and western blot. In vitro experiments using early post-natal cortical glial cultures provided further support to in vivo data and demonstrated IMT504 internalization into microglia and astrocytes. Altogether, our study provides new evidence on the central mechanisms of anti-nociception by IMT504 upon intrathecal application, and further supports its value as a novel anti-inflammatory ODN with actions upon glial cells and the TLR4/NFκB pathway. Intrathecal administration of the non-CpG ODN IMT504 fully blocks CFA-induced mechanical allodynia and hypersensitivity, in association with reduced spinal sensitization. Administration of the ODN also results in downregulated gliosis and reduced TLR4-NF-κB pathway activation. IMT504 uptake into astrocytes and microglia support the concept of direct modulation of CFA-induced glial activation.


Subject(s)
Central Nervous System Sensitization , Hyperalgesia , Animals , Hyperalgesia/drug therapy , Inflammation , Oligodeoxyribonucleotides , Pain , Rats , Rats, Sprague-Dawley , Spinal Cord
3.
Clin Transl Oncol ; 22(2): 187-192, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32006339

ABSTRACT

Cancer is one of the major public health problems in our society. It is estimated that more than 18 million new cases are diagnosed worldwide every year; 280,000 in Spain. Incidence in following a growing trend. This epidemic could be controlled with research into new treatments and, above all, with adequate prevention. Primary prevention could prevent avoid up to half of all cases. For many others, secondary prevention is essential, as it make diagnosis possible in the stages of the disease when it is easily curable. These guidelines present the scientific evidence regarding secondary prevention in tumors in which its use is well-accepted: breast, cervical, colorectal, prostate, lung, ovarian, melanoma, and gastric cancer.


Subject(s)
Clinical Trials as Topic/standards , Neoplasms/therapy , Practice Guidelines as Topic/standards , Secondary Prevention/methods , Humans , Medical Oncology , Societies, Medical
4.
J Appl Microbiol ; 126(6): 1729-1741, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30895681

ABSTRACT

AIMS: Soil biosolarization (SBS) is a pest control technology that includes the incorporation of organic matter into soil prior to solarization. The objective of this study was to measure the impact of the initial soil microbiome on the temporal evolution of genes encoding lignocellulose-degrading enzymes during SBS. METHODS AND RESULTS: Soil biosolarization field experiments were completed using green waste (GW) as a soil amendment and in the presence and absence of compost activating inoculum. Samples were collected over time and at two different soil depths for measurement of the microbial community and the predicted lignocellulosic-degrading microbiome. Compost inoculum had a significant positive effect on several predicted genes encoding enzymes involved in cellulose, hemicellulose and lignin degradation. These included beta-glucosidase, endo-1,3(4)-beta-glucanase, alpha-galactosidase and laccase. CONCLUSION: Amendment of micro-organisms found in compost to soil prior to SBS enhanced the degradation potential of cellulose, hemicellulose and lignin found in GW. SIGNIFICANCE AND IMPACT OF THE STUDY: The type of organic matter amended and its biotransformation by soil micro-organisms impact the efficacy of SBS. The results suggest that co-amending highly recalcitrant biomass with micro-organisms found in compost improves biomass conversion during SBS.


Subject(s)
Composting/methods , Environmental Restoration and Remediation/methods , Lignin/metabolism , Microbiota , Soil Microbiology , Biomass , Microbiota/genetics , Soil , Sunlight
5.
Clin Transl Oncol ; 21(1): 106-113, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30607789

ABSTRACT

Cancer is the leading social and healthcare problem of the twenty-first century. The aim of primary prevention is to decrease the incidence of cancer by avoiding the known causes and risk factors. Nevertheless, it has been estimated that cancer diagnoses could be halved through primary prevention measures. A comprehensive review of the scientific evidence regarding the main carcinogens and risk factors and primary prevention recommendations have been put forth based on this evidence. The GRADE scale has been used to classify the grade of evidence. We present the scientific evidence and recommendations for primary prevention of the major modifiable risk factors: smoking, alcohol, diet, obesity, physical activity, occupational and environmental factors, ultraviolet radiation, infections, and socioeconomic factors. Primary prevention is a simple, effective means to lower the incidence of cancer. Preventive measures must be circulated in the fight against cancer.


Subject(s)
Neoplasms/prevention & control , Practice Guidelines as Topic/standards , Primary Prevention , Clinical Trials as Topic , Disease Management , Humans , Neoplasms/etiology , Prognosis , Risk Factors , Societies, Medical
6.
Clin. transl. oncol. (Print) ; 21(1): 106-113, ene. 2019. tab
Article in English | IBECS | ID: ibc-183349

ABSTRACT

Cancer is the leading social and healthcare problem of the twenty-first century. The aim of primary prevention is to decrease the incidence of cancer by avoiding the known causes and risk factors. Nevertheless, it has been estimated that cancer diagnoses could be halved through primary prevention measures. A comprehensive review of the scientific evidence regarding the main carcinogens and risk factors and primary prevention recommendations have been put forth based on this evidence. The GRADE scale has been used to classify the grade of evidence. We present the scientific evidence and recommendations for primary prevention of the major modifiable risk factors: smoking, alcohol, diet, obesity, physical activity, occupational and environmental factors, ultraviolet radiation, infections, and socioeconomic factors. Primary prevention is a simple, effective means to lower the incidence of cancer. Preventive measures must be circulated in the fight against cancer


No disponible


Subject(s)
Humans , Primary Prevention/methods , Healthy Lifestyle , Neoplasms/prevention & control , Practice Patterns, Physicians' , Risk Factors , Tobacco Use Disorder/prevention & control , Tobacco Use Cessation , Alcohol Drinking/adverse effects , Obesity/complications , Environmental Exposure/adverse effects
8.
Clin. transl. oncol. (Print) ; 20(4): 467-475, abr. 2018. tab, graf
Article in English | IBECS | ID: ibc-171639

ABSTRACT

Purpose. Breast cancer is the most common neoplasm in women and has the highest associated mortality rate. Rapid detection programmes can provide early diagnosis and increase the chances of survival. There are no specific tumor biomarkers for the early phase of the disease. The primary aim of this study was to search a blood biomarker with levels that exceeded the normal range established in the general population that could be used to screen breast cancer. Methods/patients. Case-control study. Conventional as well as research (NGAL, EGFR and 8-OHdG) tumor biomarkers were analyzed. Results. A total of 126 women were enrolled (cases: 63 patients with local breast cancer; Controls: 63 healthy women). Significant differences were found in patients with higher levels of the conventional markers, Ca15.3, CEA, Cyfra 21.1 and NSE. However, when commercial cut-off values were used, only Ca 15.13 was significant. In the group of research biomarkers, significantly higher levels of EGFR were found in the control group, and of 8-OHdG in the case group. Using logistic regression analysis and a ROC curve, an equation composed of five markers, Ca 15.3, NSE, NGAL, EGFR and 8-OHdG, which yielded a correct diagnostic probability of breast cancer of 91.8% was obtained. Conclusions. 8-OHdG has been identified as a new potential marker for screening early stage breast cancer. In addition, a model that combines five blood markers that can be used as a diagnostic test in certain groups of patients has been developed. New studies with a larger sample size are needed to verify the results obtained (AU)


No disponible


Subject(s)
Humans , Female , Breast Neoplasms/pathology , Lipocalin-2/blood , ErbB Receptors/analysis , Deoxyguanine Nucleotides/blood , Biomarkers, Tumor/analysis , Early Detection of Cancer/methods , Oxidative Stress
9.
Clin Transl Oncol ; 20(4): 467-475, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28808872

ABSTRACT

PURPOSE: Breast cancer is the most common neoplasm in women and has the highest associated mortality rate. Rapid detection programmes can provide early diagnosis and increase the chances of survival. There are no specific tumor biomarkers for the early phase of the disease. The primary aim of this study was to search a blood biomarker with levels that exceeded the normal range established in the general population that could be used to screen breast cancer. METHODS/PATIENTS: Case-control study. Conventional as well as research (NGAL, EGFR and 8-OHdG) tumor biomarkers were analyzed. RESULTS: A total of 126 women were enrolled (cases: 63 patients with local breast cancer; Controls: 63 healthy women). Significant differences were found in patients with higher levels of the conventional markers, Ca15.3, CEA, Cyfra 21.1 and NSE. However, when commercial cut-off values were used, only Ca 15.13 was significant. In the group of research biomarkers, significantly higher levels of EGFR were found in the control group, and of 8-OHdG in the case group. Using logistic regression analysis and a ROC curve, an equation composed of five markers, Ca 15.3, NSE, NGAL, EGFR and 8-OHdG, which yielded a correct diagnostic probability of breast cancer of 91.8% was obtained. CONCLUSIONS: 8-OHdG has been identified as a new potential marker for screening early stage breast cancer. In addition, a model that combines five blood markers that can be used as a diagnostic test in certain groups of patients has been developed. New studies with a larger sample size are needed to verify the results obtained.


Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/diagnosis , Deoxyguanosine/analogs & derivatives , Early Detection of Cancer/methods , 8-Hydroxy-2'-Deoxyguanosine , Adult , Aged , Antigens, Neoplasm/blood , Breast Neoplasms/blood , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Case-Control Studies , Deoxyguanosine/blood , Female , Humans , Keratin-19/blood , Middle Aged , Phosphopyruvate Hydratase/blood , alpha-Fetoproteins/analysis
10.
Clin Transl Oncol ; 20(7): 862-869, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29178019

ABSTRACT

INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. MATERIALS AND METHODS: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.


Subject(s)
Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Drug Resistance, Neoplasm , Estradiol/analogs & derivatives , Postmenopause , Aged , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/metabolism , Carcinoma, Lobular/secondary , Estradiol/therapeutic use , Female , Follow-Up Studies , Fulvestrant , Humans , Lymphatic Metastasis , Middle Aged , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies
11.
Ecotoxicol Environ Saf ; 116: 29-33, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25748519

ABSTRACT

New Microtox® toxicity data of 16 ionic liquids of different cationic and anionic composition were determined. The ionic liquids 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate, [BMPyr(+)][TFO(-)], 1-butyl-1-methylpyrrolidinium chloride, [BMPyr(+)][Cl(-)], hydroxypropylmethylimidazolium fluoroacetate, [HOPMIM(+)][FCH2COO(-)], and hydroxypropylmethylimidazolium glycolate [HOPMIM(+)][glycolate(-)] were found to be less toxic than conventional organic solvent such as chloroform or toluene, accoding the Microtox® toxicity assays. The toxicity of pyrrolidinium cation was lower than the imidazolium and pyridinium ones. It was found that the inclusion of an hydroxyl group in the alkyl chain length of the cation also reduce the toxicity of the ionic liquid. To sum up, the Microtox® toxicity assays can be used as screening tool to easily determined the toxicity of a wide range of ionic liquids and the toxicity data obtained could allow the obtention of structure-toxicity relationships to design less toxic ionic liquids.


Subject(s)
Ionic Liquids/toxicity , Toxicity Tests , Anions , Cations , Ionic Liquids/chemistry
12.
Clin. transl. oncol. (Print) ; 17(2): 160-166, feb. 2015. tab, ilus
Article in English | IBECS | ID: ibc-132887

ABSTRACT

Background. Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited. Patients and methods. AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m2 plus paclitaxel 150 mg/m2, on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients. Results. Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9–82.0 %) and 89 % (95 % CI 80.3–95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %). Conclusions. Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response (AU)


No disponible


Subject(s)
Humans , Female , Antineoplastic Combined Chemotherapy Protocols/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Paclitaxel/therapeutic use , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/pathology , Drug-Eluting Stents , Drug Therapy, Combination , Breast Neoplasms/complications , Treatment Outcome , Evaluation of the Efficacy-Effectiveness of Interventions , Antibodies, Monoclonal/therapeutic use
13.
Gene Ther ; 22(1): 9-19, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25410742

ABSTRACT

Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC(-/-)) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC(-/-) mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC(-/-) mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC(-/-) mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC(-/-) mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury.


Subject(s)
Chemical and Drug Induced Liver Injury/metabolism , Endothelial Cells/physiology , Osteonectin/genetics , Animals , Chemical and Drug Induced Liver Injury/immunology , Concanavalin A , Endothelium, Vascular/pathology , Gene Knockdown Techniques , Lipopolysaccharides/pharmacology , Liver , Male , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Osteonectin/metabolism , Transcriptome
14.
Clin Transl Oncol ; 17(2): 160-6, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25119930

ABSTRACT

BACKGROUND: Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited. PATIENTS AND METHODS: AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients. RESULTS: Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI 80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %). CONCLUSIONS: Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Neoplastic Cells, Circulating/pathology , Receptor, Angiotensin, Type 1/metabolism , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Prognosis , Survival Rate , Translational Research, Biomedical , Gemcitabine
15.
Clin. transl. oncol. (Print) ; 14(6): 413-422, jun. 2012.
Article in English | IBECS | ID: ibc-126809

ABSTRACT

Chemotherapy-induced nausea and vomiting (CINV) is a major determinant of quality of life in cancer patients. In addition, the perceptions that oncology professionals have about CINV quite often do not coincide with reality. Antineoplastic agents and their combinations can be categorised according to their emetogenic level, and this categorisation is helpful for classifying the severity of CINV and treating it. All CINV treatment guidelines emphasise the need to administer prophylaxis to patients who receive highly or moderately emetogenic chemotherapy. With the introduction of NK1 receptor antagonists, the control of acute and delayed CINV after highly or moderately emetogenic chemotherapy schedules has improved in the great majority of patients. NK1 receptor antagonists have been demonstrated to improve the control of CINV in all risk subgroups of patients (AU)


Subject(s)
Humans , Antineoplastic Agents/adverse effects , Nausea/chemically induced , Vomiting/chemically induced , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Nausea/physiopathology , Nausea/therapy , Vomiting/physiopathology , Vomiting/therapy , Antiemetics
16.
Neurologia ; 27(2): 76-82, 2012 Mar.
Article in Spanish | MEDLINE | ID: mdl-21652121

ABSTRACT

OBJECTIVES: To study the influence of various factors on the health related quality of life (HRQOL) of patients who have suffered a brain infarction (BI), with special attention to psychopathological disorders (PD). PATIENTS AND METHODS: Prospective observational study on 45 patients admitted due to a BI, evaluated at 4, 12 and 26 weeks of the acute event. Social and demographic data, and medical history were collected; the SF-36 scale was used for the assessment of HRQOL, and the Neuropsychiatric Inventory (NPI), MMSE, Canadian Neurological Scale, Modified Rankin Scale and other instruments for assessing psychopathological, cognitive, neurological and functional status. A linear regression analysis was performed to identify potential predictors of the SF-36 scores at 26 weeks, introducing, as independent variables, medical and psychiatric history, demographic characteristics and the functional, neuropsychological and psychopathological assessments at 4 weeks. RESULTS: Valid predictive models for all the SF-36 domains were obtained, in which a history of pre-morbid depression, higher scores in the NPI and Rankin Scale, and lowest in the Canadian Neurological Scale were the main predictors of a worse HRQOL in the long term. Psychopathology related caregiver's distress (assessed with the NPI) was associated with a lower score in the social function index. CONCLUSIONS: PDs and functional status were the main determinants of HRQOL in patients with BI.


Subject(s)
Anxiety/etiology , Cerebral Infarction/psychology , Depression/etiology , Quality of Life , Aged , Anxiety/epidemiology , Brain Ischemia/psychology , Caregivers/psychology , Depression/epidemiology , Female , Humans , Linear Models , Male , Middle Aged , Neuroimaging , Neuropsychological Tests , Predictive Value of Tests , Prospective Studies , Risk Factors , Severity of Illness Index , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Surveys and Questionnaires
17.
Clin. transl. oncol. (Print) ; 10(12): 817-825, dic. 2008.
Article in English | IBECS | ID: ibc-123562

ABSTRACT

INTRODUCTION: Treatment of HER-2-negative metastatic breast cancer (MBC) patients after anthracycline exposure is controversial. Docetaxel/capecitabine is a promising regimen, but the administration schedule is not well established. MATERIALS AND METHODS: Treatment included 3 cycles of docetaxel 100 mg/m2 day 1 every 21 days followed by 3 cycles of capecitabine 1250 mg/m2/12 h days 1-14. Patients not progressing were maintained with capecitabine 900 mg/m2/12 h on days 1-14 every 21 days until progression or unacceptable toxicity. RESULTS: Fifty-three anthracycline-pretreated patients were enrolled: median age 54 years, ECOG grade 0-1 86.7%. Most of the women received adjuvant chemotherapy (81%) and 5 patients (9%) had had prior metastatic chemotherapy treatment. Median time from anthracycline exposure was 29 months. ORR (intent-to-treatment analysis) after the sequential therapy was 51% (CI 95% 37-65) with 15% (CI 95% 7-28) of patients reaching complete responses. Median time to progression was 8.2 (CI 95% 7.1-10.7) months, with 61.9% (CI 95% 45.6-76.4) of the patients free of disease after 6 months. Median overall survival was not reached after a median follow-up of 10.4 months, and 75% of the patients were alive after 14.3 months. Survival rate after 12 months was 81.1% (CI 95% 68.0-90.6). The most frequent NCI grade 3-4 toxicities were hair loss (28.3%), asthenia (15.1%), stomatitis (11.32%) and nausea (11.32%). Severe hand-foot syndrome rate was 7.5%. CONCLUSIONS: Sequential docetaxel-capecitabine is feasible, effective and well tolerated in first-line MBC treatment. Evaluation of this schedule in randomised studies is warranted (AU)


No disponible


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Anthracyclines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , /metabolism , Taxoids/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Dose-Response Relationship, Drug , Deoxycytidine/adverse effects , Drug Administration Schedule , Fluorouracil/adverse effects , Neoplasm Metastasis
18.
J Agric Food Chem ; 56(13): 5266-72, 2008 Jul 09.
Article in English | MEDLINE | ID: mdl-18540620

ABSTRACT

Kinetic studies are of great concern for understanding the processes and parameters involved in the sorption of pollutants by soils. Sorption kinetics of imidacloprid and diuron in eight soils of different characteristics, with very low organic carbon content were investigated. Pseudosecond-order kinetic reactions closely correlate with the experimental kinetic (R(2) > 0.98) in all soils. The sorbed amount of diuron was higher than that for imidacloprid. The low OC content of these soils correlated neither with the sorbed amount nor with the kinetic parameters for both pesticides. Imidacloprid sorption was correlated with silt and sand content and cation exchange capacity (CEC); meanwhile for diuron, no correlation was found. Thus, sorption kinetics take place throughout different mechanisms related mainly to the chemical character of the pesticides. Sorption kinetic parameters determined using three of the four models selected (pseudosecond-order kinetic reactions, Elovich equation, and Weber-Morris models) have been shown to be worthy to distinguish the process controlling the sorption kinetic of both pesticides.


Subject(s)
Diuron/analysis , Environmental Pollutants/analysis , Imidazoles/analysis , Nitro Compounds/analysis , Soil/analysis , Adsorption , Chromatography, High Pressure Liquid , Kinetics , Models, Biological , Models, Theoretical , Neonicotinoids , Pesticides/analysis , Spain
19.
Cancer Chemother Pharmacol ; 62(6): 1085-90, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18365200

ABSTRACT

BACKGROUND: Addition of carboplatin (C) to trastuzumab (T) and paclitaxel (P) improves the efficacy in HER2+ metastatic breast cancer (MBC). The aim of this phase-II study was to evaluate the efficacy and safety of this combination given weekly (3x) followed by a week off. The primary endpoint was: objective response rate (ORR), and secondary endpoints were: time to progression (TTP), overall survival (OS), and toxicity profile. METHODS: HER2+ MBC patients were included in the study. Treatment was as follows: T (loading dose:4 mg/kg per week and 2 mg/kg per day thereafter), P (80 mg/m(2)) and C (AUC 2) given weekly 3x, followed by 1 week off until disease progression or unacceptable toxicity. RESULTS: Forty-one patients (pts) were enrolled-median age: 54.5 years (range 29-75); 87.8% PS 0 or 1; 39 (97.5%) had received prior adjuvant or neoadjuvant treatment; 11 (27%) had received one prior CT line for metastatic disease; disease sites: liver (40%), bone (32.5%), lymph nodes (32.5%) and lung (20%); 19 (47.5%) had > or =2 lesions and 97.5% had measurable disease. A total of 37 pts were evaluated for response: 11(26.8%) CR; 12 (29.3%) PR; 9 (22%) SD; 5 (12.2%) PD and 4 NE, resulting in an ORR of 56.1% (95% CI 39.7-71.5%) and tumor growth control rate (RR + SD) of 78% (95% CI 62.4-89.4%). With a median follow up of 39.4 months, 26 (70.3%) patients have progressed. The median time to progression was 12.3 months (95% CI 8.2-15.5). At the time of this report, ten patients have died. Forty patients received 202 cycles (median five cycles). Grades 3-4 toxicities/pts: 3 (7.5%) anemia, 2 (5%) leucopenia, 10 (25%) neutropenia, 1 (2.5%) febrile neutropenia,1 (2.5%) thrombopenia, 2 (5%) asthenia, 2 (5%) diarrhea, 3 (7.5%) nausea, 2 (5%) vomiting, and 3 (7.5%) mucositis. CONCLUSIONS: The schedule showed an interesting activity, taking into account that 27% of patients had received previous treatment for MBC. One week of rest may benefit not only the patient but may also improve tolerability and efficacy of the combination.


Subject(s)
Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Genes, erbB-2 , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carboplatin/administration & dosage , Carboplatin/adverse effects , Disease Progression , Female , Gastrointestinal Diseases/chemically induced , Half-Life , Hematologic Diseases/chemically induced , Humans , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Peripheral Nervous System Diseases/chemically induced , Survival Analysis , Trastuzumab
20.
Environ Pollut ; 154(2): 330-7, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18023948

ABSTRACT

The influence of two vermicomposts from winery and distillery wastes on the distribution of diuron in agricultural soil was studied. Physical soil fractionations at 0, 9, 27, 49 and 77 days, allowed the quantification of pesticide residues in different particle-size fractions, coarse waste (WF), sand-sized (SF), silt-sized (SiF), clay-sized (CF) and dissolved organic matter-sized fraction (DOM). The SiF made a greater contribution to the formation of non-extractable residues in unamended soil, but when vermicomposts were added, new sorption sites in WF appeared, being higher for the more humified vermicompost V2. The dissolved organic carbon (DOC) increased with the addition of vermicompost, but the concentration of the desorbed 14C-radiochemical did not increase. Non-significant increment was observed with time for the non-extractable fraction with amendments. Diuron was transformed in all samples, although less than 0.5% was mineralized. The main effect caused by vermicomposts was a reduction in the availability of diuron in soil.


Subject(s)
Beer , Diuron/analysis , Environmental Restoration and Remediation/methods , Industrial Waste , Pesticides/analysis , Soil Pollutants/analysis , Soil/analysis , Wine , Adsorption , Agriculture , Carbon , Ecosystem , Environmental Monitoring/methods , Humic Substances , Particle Size , Solubility
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