Increase in Anti-Gal IgM Level is Associated With Early Graft Failure in Intraportal Porcine Islet Xenotransplantation

BACKGROUND: Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx). METHODS: Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA. RESULTS: The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003). CONCLUSIONS: IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF.

Non small cell lung cancer molecular biomarkers in blood

Several studies have reported significant correlations between individual telomerase activity and apoptosis in malignant tumours including lung cancer. Such studies were carried out on tissue biopsies from the malignant tissue. The aim of the present study was to determine molecular biological parameters that can he used for early biological predisposition for lung cancer. Telomerase activity and Bcl-2 anti-apoptotic protein in circulating lymphocytes, plasma nitric oxide. epidermal growth factor and epidermal growth 'actor receptor were measured in the blood of 25 non small cell lung cancer [NSCLC] patients amid in 20 normal age and socio-economic matching controls, Results revealed significant increase in telomerase activity [53 +/- 8.2 vs. 19.5 +/- 4.8. p<0.0001] between cancer patients and normal controls, significant lower levels of Bcl-2 [7 2 +/- 1,5 vs. 10.4 +/- 1.4 micro g/ml, t 7.3. p<0.0000001] among cancer patients compared to normal controls, However, there were significantly higher levels of epidermal growth factors [6.2 +/- 2 05 vs 0.2 +/- 0.01 pg/ml], epidermal growth factor receptor EGFR [134 +/- 4.7 vs. 102 +/- 2.2 fmol/ml] and plasma nitrate/nitrite [18.8 +/- 4.7 vs. 12.5 +/- 5 micro g/ml. 1=-5.25. p<0.0001] in lung cancer patients compared to controls. This study reveals that Bcl-2 levels in circulating peripheral blood are weak biomarkers for lung cancer, while increase in plasma telomerase activity, NO and EGF levels can he used as reliable biomarkers for cancer prognosis

Serum epidermal growth factor in cancer breast

Several prognostic factors are evaluated in the breast carcinoma and there is a need o- new markers for better discrimination of the biologic differences in the primary tumor. Epidermal growth factor [EGF] is presumed to play an important role in the local regulation of cell proliferation so, the aim of the current study, was to evaluate the serum level of EGF in breast cancer female patients in comparison with other prognostic parameters. It was carried out r fifty-seven females divided into two groups. A control group of twenty healthy women of comparable age and socioeconomic status with a group of thirty-seven breast cancer patients. All females were chosen non-pregnant, not on contraceptive therapy, not previously exposed to radiation, and have no previous history of cancer. To all patients, thorough clinical examination, plain X-ray for the chest and ultrasonography of the abdomen and pelvis were done. Preoperative fine needle aspiration cytology was also done for their breast lumps. In addition, blood samples where collected and analyzed for hemoglobin, fasting serum glucose, urea, and creatinine levels, aspartate and alanine aminotransferase activities, and also the epidermal growth factor level. The breast cancer tissues, removed by surgery, were subjected to histopathologic examination. The median of serum EGF in breast cancer patients group was relatively lower than that in control group but it did not reach the level of significance. No significant differences between the serum EGF levels were found in relation to the change in tumor size, type, grade, and stage. However, there was positive correlations between EGF level and tumor size [r=0.341, p=0.039] and AJCC stages [r0.354, p=0.032]. Also, in patients without lymph node metastasis, there were positive correlations between serum EGF level and both tumor size [r=0.596, p=0.024] and AJCC stages [r=0.596, p=0.024]. In patients having lymph node metastasis, there was significant negative correlation between serum EGF level and the number of lymph node metastasis [r=-0.859, p<0.001].There was significant increase in EGF level in patients having lymph node metastasis [3 LN] metastasis was significantly increased than that in both patients having no LN metastasis [p=0.01 9] and patients having

Bioquímica del líquido quístico mamario, III: niveles del factor de crecimiento epidérmico, gonadotrofina coriónica y andrógenos conjugados / Biochemistry of breast cyst fluids, III: levels of NA, K, androgens, epidermal growth factor and human chorionic gonadotropin

En la última década se ha implementado una serie de análisis bioquímicos que permiten identificar varios tipos de líquidos quísticos (LQs). En el presente trabajo se confirma la presencia de polipéptidos y esteroides conjugados -como el factor de crecimiento epidérmico (FCE), el sulfato de dehidroepiandrosterona (S-DHEA) y el androstano-3Ó, 17ß-diol glucurónido (3Ó-Adiol G)- a veces en concentraciones muy elevadas con respecto a los niveles encontrados simultáneamente en el plasma circulante. Como contraste, la concentración del cortisol apenas alcanza a un 20 por ciento del normalmente hallado en el plasma. Se demuestra además que la concentración intraquística del 3Ó-Adiol G se correlaciona positiva y significativamente con la del S-DHEA (r = 0,8744, p < 0,0001) y con el FCE (r = 0,8949, p < 0,0001), con amplia variabilidad en los resultados. Se establece también una correlación negativa entre el 3Ó-Adiol G y el cociente Na/K (r = - 0,6592, p = 0,0001). Por último, se determinan los niveles de la gonadotrofina coriónica (hCG), utilizando un sistema automatizado de quimioluminiscencia, demostrándose que esta glicoproteína se encuentra en cantidades determinables (> 1,1 mUI/ml) en el 73,8 por ciento de los LQs analizados. En el 57,4 por ciento los niveles superan a los encontrados normalmente en el plasma que oscilan entre < 1,1 mUl/ml y 5,5 mUl/ml. En un 4,9 por ciento las concentraciones resultan significativamente elevadas, alcanzando hasta las 1.000 mUl/ml. Se demuestra una correlación negativa con alta significación estadística entre los valores normalizados de la hCG con los niveles del S-DHEA, del 3Ó-Adiol G y del FCE y una correlación positiva con el cociente NA/K. Se discute la posibilidad de que el FCE, los esteroides conjugados y la hCG puedan ser sintetizados de novo en el tejido epitelial que recubre las paredes del quiste