Safety of anti-varicella zoster virus vaccination in patients with multiple sclerosis treated with natalizumab: A case series.

The vaccination with live attenuated vaccines is generally not recommended during natalizumab (NTZ), as it is included among immunosuppressive/immunomodulating therapies. Nevertheless, considering the lack of evidence of a non-Central Nervous System (CNS) immunosuppressive effect of NTZ, after a risk/benefit evaluation, we decided to vaccinate four multiple sclerosis (MS) patients (three with an indication to switch to ocrelizumab for high-risk Progressive Multifocal Leukoencephalopathy (PML) and one for pregnancy planning). No vaccine-related adverse events of any type nor varicella zoster virus (VZV) infections were observed. To the best of our knowledge, these case series represent the first description of the good safety profile of anti-VZV vaccination in MS patients during NTZ treatment.

Overexpression of both CXC chemokine receptor 4 and vascular endothelial growth factor proteins predicts early distant relapse in stage II-III colorectal cancer patients.

PURPOSE: CXC chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) are implicated in the metastatic process of malignant tumors. However, no data are currently available on the biological relationship between these molecules in colorectal cancer. We studied whether CXCR4 and VEGF expression could predict relapse and evaluated in vitro the contribution of CXCR4 in promoting clonogenic growth, VEGF secretion, and intercellular adhesion molecule-1 (ICAM-1) expression of colorectal cancer cells. EXPERIMENTAL DESIGN: CXCR4 and VEGF were studied in colorectal cancer tissues and in Lovo, HT29, and SW620 colorectal cancer cell lines by immunohistochemistry. Correlations with baseline characteristics of patients and tumors were analyzed by chi2 test. VEGF secretion induced by CXCL12 was measured by ELISA. The effect of CXCL12 on ICAM-1 expression was evaluated by flow cytometry. Clonogenic growth induced by CXCL12 was determined by clonogenic assays. Functional effects induced by CXCL12 were prevented by the administration in vitro of AMD3100, a bicyclam noncompetitive antagonist of CXCR4. RESULTS: Seventy-two patients, seen between January 2003 and January 2004, were studied. CXCR4 was absent in 16 tumors (22.2%); it was expressed in < or = 50% of cells in 25 (34.7%) tumors and in >50% of cells in 31 (43.0%) tumors. VEGF was absent in 17 (23.6%) tumors; it was expressed in < or = 50% of cells in 16 (22.2%) tumors and in >50% of cells in 39 (54.2%) tumors. There was a significant association between CXCR4 expression and lymph nodal status (P = 0.0393). There were significant associations between VEGF and tumor invasion (P = 0.0386) and lymph nodal involvement (P = 0.0044). American Joint Committee on Cancer stage (P = 0.0016), VEGF expression (P = 0.0450), CXCR4 expression (P = 0.0428), and VEGF/CXCR4 expression (P = 0.0004) had a significant prognostic value for disease-free survival with univariate analysis. The predictive ability of the American Joint Committee on Cancer stage and of the concomitant and high expression of VEGF and CXCR4 was confirmed by multivariate analysis. Prognosis is particularly unfavorable for patients whose primary tumors express CXCR4 and VEGF in >50% of cells (median disease-free survival in relapsed patients, 5.8 months; hazard ratio of relapse, 8.23; 95% confidence interval, 7.24-14.29). In clonogenic assays, CXCL12 (20 ng/mL/d) significantly increased the number of clones in SW620, HT29, and Lovo cells at 7 and 14 days. Again, CXCL12 was able to stimulate VEGF secretion in SW620, HT29, and Lovo cells as well as up-regulated ICAM-1. These effects were prevented by the administration of AMD3100 (1 micromol/L). CONCLUSIONS: We have shown that concomitant and high expression of CXCR4 and VEGF is a strong and independent predictor of early distant relapse in colorectal cancer. CXCR4 triggers a plethora of phenomena, including stimulation of clonogenic growth, induction of VEGF release, and ICAM-1 up-regulation. These data support the inhibition of CXCR4 to prevent the development of colorectal cancer metastasis.

Has lung cancer in the elderly different characteristics at presentation?

Lung cancer is the first cause of cancer death for males aged > or =35 years, and the second for females aged between 35 and 70 years. Elderly patients seem to have the worst performance status (PS) and earlier stage of disease at diagnosis. We analyzed data concerning 1,035 patients with lung cancer referred to the National Cancer Institute of Naples. The variables considered in the analysis were: gender; type of cancer [small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC)]; ECOG (Eastern Cooperative Oncology Group) PS, the stage of disease at diagnosis, the histological type, age at diagnosis. In order to better assess the relevance of age at diagnosis in lung cancer patients we categorized the age into two groups (young < or =70; old >70 years). The statistical analyses were performed using chi2 trend test with corresponding p-value and odds ratios (OR) for the examined variables, with a corresponding 95% confidence interval. These were derived using multiple logistic regression, fitted by the maximum likelihood method. For all the 1035 patients the risk between the age at diagnosis and the performance status was not statistically significant (OR=1.1, 95%CI 0.8-1.5). We repeated the same risk distinguishing the histological type and we analyzed the performance status for the SCLC (OR=1.0, 95%CI 0.4-2.5) and the stage at diagnosis (OR=1.0, 95%CI 0.4-3.0), without any significant difference. Our study showed that elderly patients with lung cancer do not seem to have different characteristics at presentation, particularly related to stage of disease, PS and histology, as compared to their younger counterpart. Other characteristics such as type and number of co-morbidities and organ function differ in the two groups of populations.