Low immunogenicity of seasonal trivalent influenza vaccine among patients receiving docetaxel for a solid tumour: results of a prospective pilot study.

BACKGROUND: Patients receiving cytotoxic therapy for solid tumours are at risk of severe influenza. However, few data are available regarding the immunogenical efficacy of influenza vaccine in these patients. METHODS: In this prospective study, 25 patients with breast (n=13) or prostate (n=12) cancer received a trivalent inactivated influenza vaccine along with docetaxel (Taxotere) administration. The influenza virus type A and B antibody titres were measured using haemagglutinin inhibition (Garten et al, 2009) before and 21 days after the vaccination. Seroconversion rate was defined as the percentage of patients with an increase in the serum titres ≥ 4 after vaccination. RESULTS: Median age was 65 years (range: 33-87 years); 52% were females. Seroconversion rates were low: 28% (95% CI: 23.1-33.3) for H1N1, 8% (95% CI: 7.7-8.3) for H3N2 and 16% (95% CI: 7.7-25) for the B strain. The geometric mean titres ratios were 2.16 (H1N1), 1.3 (H3N2) and 1.58 (B). No serious adverse event (AE) related to the vaccine was reported. All the reported AE were from mild-to-moderate intensity. CONCLUSION: In the patients receiving docetaxel for solid tumours, influenza vaccine triggers an immune response in only one third. Strategies using more immunogenic influenza vaccines must be evaluated in such patients.

[Dynamic circadian system patients under chimiotherapy]. / Dynamique du système circadien de patients sous chimiothérapie.

Currently, the circadian timing system of cancer patients can be estimated with wrist actimetry, which provides numerical data on the continuous activity of patients. The method of processing of these data, which we implemented, aims at answering the following questions: is the circadian timing system stable before chemotherapy, is this system extensively modified by chemotherapy, are there structural modifications or a decrease in activity amplitude produced by chemotherapy and how does the circadian activity rhythm recover? Here, we determine a circadian model function using a wavelet transform prior to chemotherapy delivery. Then we measure the correlation between this model function and the evolution of the circadian rhythm of activity over the whole observation span during and after chemotherapy. The application of this method to the record of activity rhythms in cancer patients highlights the characteristics and the recovery pattern of chemotherapy-induced alterations of the circadian timing system.

Cross-talks between circadian timing system and cell division cycle determine cancer biology and therapeutics.

The circadian clock orchestrates cellular functions over 24 hours, including cell divisions, a process that results from the cell cycle. The circadian clock and cell cycle interact at the level of genes, proteins, and biochemical signals. The disruption or the reinforcement of the host circadian timing system, respectively, accelerates or slows down cancer growth through modifications of host and tumor circadian clocks. Thus, cancer cells not only display mutations of cell cycle genes but also exhibit severe defects in clock gene expression levels or 24-hour patterns, which can in turn favor abnormal proliferation. Most of the experimental research actively ongoing in this field has been driven by the original demonstration that cancer patients with poor circadian rhythms had poor quality of life and poor survival outcome independently of known prognostic factors. Further basic research on the gender dependencies in circadian properties is now warranted, because a large clinical trial has revealed that gender can largely affect the survival outcome of cancer patients on chronotherapeutic delivery. Mathematical models further show that the therapeutic index of chemotherapeutic drugs can be optimized through distinct delivery profiles, depending on the initial host/tumor status and variability in circadian entrainment and/or cell cycle length. Clinical trials and systems-biology approaches in cancer chronotherapeutics raise novel issues to be addressed experimentally in the field of biological clocks. The challenge ahead is to therapeutically harness the circadian timing system to concurrently improve quality of life and down-regulate malignant growth.

Immunohistochemical and serological 90K/Mac-2BP detection in hepatocellular carcinoma patients: different behaviour of two monoclonal antibodies.

To clarify the biological role of the 90K/Mac-2BP glycoprotein, we evaluated the ability of two MAbs SP-2 and 1A4.22, to reveal this glycoprotein in both serum and tissue from hepatocellular carcinoma (HCC) patients. Tissue expression of 90K was detected by the immunohistochemical method in 20 HCC patients, while the 90K serum level was assessed by the ELISA assay in 13 HCC patients. MAb SP-2 was reactive only in serum, with a mean value of 12.8+/- 6.7 microg/ml . On the contrary, MAb 1A4.22 revealed immunoreactivity both in 92% of sera and in 60% of neoplastic samples. Positive staining was seen only in the epithelial cells and was cytoplasmic and granular in all instances. The mean 90K serum level assayed with MAb 1A4.22 was 29.4 +/- 13.7 microg/ml. Patients with a 90K serum level 30 microg/ml. Moreover, a possible poor prognostic role was observed for negative 90K in tissue. Our results suggest that only MAb 1A4.22 could demonstrate 90K glycoprotein expression in paraffin-embedded tissue and that this MAb could have a diagnostic and prognostic role in both sera and tissues from HCC patients.

Concentrations of galectin-3 in the sera of normal controls and cancer patients.

Galectin-3, a member of the beta-galactoside-binding animal lectins, has been implicated in tumor invasion and metastasis. Using an immunoligand assay, we assessed the circulating levels of galectin-3 in sera from cancer patients as well as from healthy controls. Low serum levels of galectin-3 were detected in healthy individuals (median, 62 ng/ml; range, 20-313 ng/ml; 95th percentile, 184.3 ng/ml). Compared with healthy individuals, galectin-3 serum levels in patients with breast, gastrointestinal, lung, or ovarian cancer, melanoma, and non-Hodgkin's lymphoma were significantly elevated (P = 0.014). Moreover, galectin-3 concentrations in sera from patients with metastatic disease were higher than in sera from patients with localized tumors. Maximum serum concentrations of galectin-3 (median, 320 ng/ml; range, 20-950 ng/ml) were found in patients with metastatic gastrointestinal carcinoma. These results suggest that circulating galectin-3 may play a role in tumor progression. The possibility of using this assay in early-stage cancer to predict metastasis should be studied.