Biomedical subjects

José Lastiri

Publications and source records attributed to José Lastiri.

6 recordsLinked to original sources

PubMed2007

Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors.

The neural cell adhesion molecule (NCAM) is involved in the intercellular junctions of neurons and glial cells. We investigated its relevance as a biomarker in gliomas which main characteristic is their high invasiveness. We studied by Western blot the pattern of serum NCAM bands in patients with gliomas (n = 34), with brain metastasis of different primary cancers (n = 27) and with benign brain tumors (n = 22)] compared with healthy controls (n = 69). For densitometric analysis NCAM bands > or = 130 kDa (HMW) and <130 kDa (LMW) were clustered. We observed that glioma patients presented higher NCAM HMW and lower NCAM LMW levels than control subjects (P < 0.01). A similar pattern was found in patients with brain metastasis or brain benign tumors, suggesting that the pattern of serum NCAM bands would be useful to detect brain tumor pathology. On the other hand, serum NCAM expression was not associated with the main clinicopathological features of gliomas, including overall survival. Interestingly, we found that 9/12 patients with glioma showed a significant decrease in NCAM HMW/LMW ratio between 1-3 months after successful tumor removal. Thus, serum NCAM could be a useful marker for monitoring treatment.NCAM expression was also analyzed at tissular level in 59 glioma sections from paraffined tumors. We observed that NCAM immunostaining was inversely correlated with the histological grade of malignancy, remaining this association in a multivariate analysis. Besides, loss of NCAM staining was significantly associated with bad prognosis in an univariate analysis.

Adult↗

PubMed2006

Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2) in patients with colorectal carcinoma.

BACKGROUND AND OBJECTIVES: Therapy of colorectal tumors (CRC) based on histology and clinical factors is insufficient to predict the evolution of each patient. The finding of molecular abnormalities able to differentiate subgroups of patients with bad prognosis will improve our ability to treat them successfully. Our purpose was to analyze retrospectively the prognostic input of E-cadherin, beta-catenin, metalloproteinases (MMPs) (7 and 9), and tissue inhibitors of metalloproteinases (TIMPs) (1 and 2) in patients with a follow-up period of 5 years. METHODS: Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate proportional hazards model. RESULTS: We demonstrated a concomitant loss of E-cadherin and beta-catenin at membranous level and an abnormal accumulation of nuclear beta-catenin. Besides, we found that all MMPs and TIMPs studied were overexpressed in CRC tissue. There was no association between the expression of any of these molecules and the known clinical-pathological parameters employed in CRC pathology. A multivariate analysis demonstrated that the overall survival could be independently predicted by the loss of E-cadherin and the overexpression of TIMP-2. CONCLUSIONS: The expression of E-cadherin and TIMP-2 could be relevant in determining the prognosis of CRC patients and providing a more accurate mechanism for their classification.

Adult↗

PubMed2004

EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas.

BACKGROUND AND OBJECTIVES: Therapy of malignant glioma tumors is based on histology and clinical factors. However, comparable lesions may correspond with important prognostic differences. Our purpose was to analyze retrospectively the prognostic input of platelet-derived growth factor receptor (PDGF-R), epidermal growth factor (EGF-R), and bcl-2 expression in 103 malignant gliomas from uniformly treated patients. METHODS: The expression of the antigens was analyzed by immunohistochemistry (IHC). Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5-122) months for survivors. RESULTS: We observed that almost 50% of gliomas showed high expression of PDGF-R, while a lower expression of EGF-R and bcl-2 was found. No association between the main prognostic factors in malignant glioma (sex, age, histological grade, and Karnofsky score) and the labeling index (LI) of these antigens was observed. We found that only PDGF-R and EGF-R overexpression were associated with a shorter survival in patients with World Health Organization (WHO) II astrocytomas, being both associations independent of known prognostic factors, as shown by Cox model. Besides, we confirmed other authors' results that high histological grade and low performance score were associated with worse prognosis. CONCLUSIONS: PDGF-R and EGF-R expression could be relevant in determining the prognosis of low-grade astrocytomas (LGAs) and in providing a more objective mechanism for their classification.

Adolescent↗

PubMed2004

Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type.

Memory impairment is a process associated with alterations in neuronal plasticity, synapses formation, and stabilization. As the neural cell adhesion molecule (NCAM) plays a key role in synaptic bond stabilization, we analyzed the usefulness of soluble NCAM isoforms in the diagnosis of patients with dementia of the Alzheimer type (DAT). NCAM was measured in the sera of 70 control subjects and 43 DAT patients (with different severity of cognitive impairment, GDS), employing Western blot and densitometric quantification. LMW-NCAM bands (100-130 kDa) decreased significantly with age independently of sex. DAT patients presented values of LMW-NCAM and HMW-NCAM significantly higher than healthy controls of similar age (higher than 130 kDa). Only LMW-NCAM was associated with GDS. Our results suggest that NCAM could be involved in the pathogenesis of DAT disorder and that serum NCAM levels could be useful as differential diagnostic markers of the disease.

Adult↗

PubMed2004

Prognostic value of Mdm2, p53 and p16 in patients with astrocytomas.

Surgical cure of gliomas infiltrating into the brain is practically impossible and their clinical course is primarily determined by the biological behavior of the tumor cell. The purpose of this study was to analyze retrospectively prognostic input of p53, Mouse double minute-2 (Mdm2) and p16 in 103 uniformly treated patients with astrocytic tumors. The expression of these molecules was measured by immunohistochemical procedure. Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5-122) months for the survivors. We observed that 66% of gliomas showed mutated p53, while only 17% overexpressed Mdm2, the p53-regulatory molecule. Besides, almost 50% of gliomas lost p16 immunopositivity. Only p53 labeling showed a positive correlation with the grade of malignancy, according with the WHO classification. The association between mutated p53 and histological grade remained when prognostic variables were considered in a multivariate analysis. No association between p53 status and overall survival was found. On the other hand, Mdm2 overexpression and, unexpectedly, p16 immunopositivity were associated with a shorter survival in an univariate analysis. However, Cox-regression analysis showed that only Mdm2 in female patients was an independent prognostic factor, associated with shorter survival. In conclusion, our results suggest that Mdm2 could be a relevant marker in determining the evolution of glioma patients and could provide a more objective way to classify astrocytomas.

Adolescent↗

PubMed2002

CD44 expression in human gliomas.

BACKGROUND AND OBJECTIVES: Glioma invasiveness involves the attachment of tumor cells to the brain extracellular matrix, rich in hyaluronic acid (HA). CD44, the principal receptor for HA is found as a standard molecule (CD44s) or as variants (CD44v). We undertook a retrospective study to evaluate the expression pattern of CD44s, the isoforms CD44v3, v4/5 and v6 and to correlate their expression with clinical-anatomopathological parameters and survival rate. METHODS: The expression of these molecules was evaluated immunohistochemically in 84 gliomas. RESULTS: No expression of CD44v was detected in any tumors. CD44s staining of tumor cells was found in 70 of 84 (83.3%) of the gliomas. In 23 of 39 (59.0%) of the GBM more than the 70% of the cells were stained, while only 2 of 21 (9.5%) of LGA showed high expression. The association between CD44 and histological grade remained when the prognostic variables were considered in a multivariate analysis. Higher expression of CD44 was associated with worse overall survival rate; however, the Cox analysis indicated that survival was not associated with CD44. CONCLUSIONS: Our results suggest that overexpression of CD44s could be relevant in determining the highly invasive behaviour of gliomas, though it does not behave as an independent prognostic factor for survival.

Adolescent↗