Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients

Matrix metalloproteinases (MMP) have been implicated in tumor invasion and metastasis. We verified, by gelatin zymography, MMP activity in the euglobulin plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149 patients with breast, lung, colon or brain cancer. The euglobulin fractions assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md) value for 92 kDa-MMP activity was significantly increased in breast (Md 1.34 arbitrary units [AU]/ml plasma, range 0.0–7.2) and lung cancer patients (Md 1.43 AU/ml, range 0.0–3.6) compared with the controls (Md 0.48 AU/ml, range 0.0–1.8). Patients with colon cancer or gliomas presented values of MMP-9 similar to those of the healthy population. Multivariate analysis indicated that plasma MMP-9 activity was not predicted by the known clinicopathological parameters such as age, stage, tumor size, number of positive lymph nodes, histologic grade, histologic type, nuclear grade or mitotic index. Lung cancer patients also presented high values of MMP-9 (Md 1.43, range 0.0–3.6 [n = 26]), without association with tumor stage or histologic type. The levels of 92 kDa-MMP activity in the plasma euglobulin fraction could be a potentially useful tumor marker in breast and lung cancer.Fil: Farias, Eduardo Francisco. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ranuncolo, Stella Maris. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cresta Morgado, Carlos. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Specterman, Sergio. Hospital Italiano; ArgentinaFil: Armanasco, Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Varela, Mirta. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lastiri, José. Hospital Italiano; ArgentinaFil: Pallotta, María Guadalupe. Hospital Italiano; ArgentinaFil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentin

Estrogen receptor β and epidermal growth factor receptor as early-stage prognostic biomarkers of non-small cell lung cancer

As 20% of stage I NSCLC patients develop recurrent and often incurable cancer, the identification of prognostic markers has a meaningful clinical application. The biological significance of steroid hormone and EGF receptors, able to regulate key physiological functions, remains elusive in NSCLC. Our aim was to investigate the prognostic input of estrogen receptors (ER·, ERß), progesterone receptors (PR) and EGFR in tumors from 58 stage I NSCLC patients. Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate Cox model. We found that about 70 and 40% of samples expressed ER· or ERß at cytoplasmic or nuclear level, respectively. Besides, only 12.1% of samples weakly expressed nuclear PR and 62.7% showed membrane EGFR staining. Correlation studies indicated an inverse association between EGFR expression and smoking status (p<0.01). Multivariate studies showed that the lack of nuclear ERß or the loss of EGFR expression were independent prognosis markers associated with shorter overall survival. We also found that patients whose tumors were negative for these two biomarkers presented the worst outcome. In conclusion, our findings could be useful for selecting stage I NSCLC patients with poor prognosis to apply an earlier treatment that impacts on survival.Fil: Mauro, Laura Valeria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dalurzo, Mercedes. Hospital Italiano; ArgentinaFil: Carlini, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Smith, David. Hospital Italiano; ArgentinaFil: Núñez, Myriam Carmen. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Simian, Marina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Lastiri, José. Hospital Italiano; ArgentinaFil: Vasallo, Bartolomé. Hospital Italiano; ArgentinaFil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pallotta, María Guadalupe. Hospital Italiano; ArgentinaFil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

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.Fil: Todaro, Laura Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Puricelli, Lydia Ines. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Gioseffi, Hernan. Hospital Italiano; ArgentinaFil: Pallotta, María Guadalupe. Hospital Italiano; ArgentinaFil: Lastiri, José. Hospital Italiano; ArgentinaFil: Bal de Kier Joffe, Elisa. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Varela, Mirta. Hospital Italiano; ArgentinaFil: Sacerdote de Lustig, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaUnidad documental simpl

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. (c) 2006 Wiley-Liss, Inc.Fil: Bravo Roca, María Fernanda. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Mauro, Laura Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Morandi, Ana. Hospital Italiano; ArgentinaFil: Bonadeo, Fernando. Hospital Italiano; ArgentinaFil: Vaccaro, Carlos Alberto. Hospital Italiano; ArgentinaFil: Quintana, Guillermo Ojea. Hospital Italiano; ArgentinaFil: Specterman, Sergio. Hospital Italiano; ArgentinaFil: Bal, Elisa Dora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; ArgentinaFil: Pallotta, María Guadalupe. Hospital Italiano; ArgentinaFil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Lastiri, José. Hospital Italiano; Argentin

Alteración en los niveles de N-CAM soluble en pacientes con tumores cerebrales

En 1824 Dutrochet informó acerca de la capacidad que poseen los leucocitos de adherirse a las paredes de los vasos y de migrar a los tejidos circundantes...Fil: Todaro, Laura Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Puricelli, Lydia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Pallotta, María Guadalupe. Hospital Italiano; ArgentinaFil: Lastiri, José. Hospital Italiano; ArgentinaFil: Ciraolo, C.. Hospital Italiano; ArgentinaFil: Lopez Lincuez, Maria Emilia. Hospital Italiano; ArgentinaFil: Bal de Kier Joffé, E.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Sacerdote de Lustig, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valera, M. S.. Hospital Italiano; Argentin