Structure and function relationships of mutations in human melanocortin receptors 1 and 2

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Health-related quality of life of a very special population: monks of Holy Mountain Athos, Greece

The investigation of Health-Related Quality of Life (HRQOL) of Orthodox Christian monks who live at the Holy Mount Athos in Greece, and its correlation with demographic characteristics and Sense of Coherence (SOC-13). A cross-sectional study was designed. The seven monasteries and five scetes with the largest number of monk population were invited to participate. Two monasteries and 1 scete gave their permission for the study. The final monks sample was formed by 166 monks from 215 who participated to the study. HRQOL was assessed using the SF-12 and Sense of Coherence the SOC-13 scales that were completed by monks from May to August 2012. Ieultiple linear regression analyses were conducted to explore the association of the HRQOL subscales with the demographics and SOC-13. The mean age was 45.5 +/- 13.0 years; 83.7% lived in communal monasteries, and the mean number of years in monasticism was 18.4 +/- 12.1. The mean value of their Physical Component Summary (PCS) score was 47.3 +/- 5.3, which is lower than in the general Greek men population, while their Mental Component Summary (MCS) score was 56.4 +/- 5.8, which is higher than in the general Greek men population. The mean value of SOC-13 was 65.7 +/- 6.5. Positive association for PCS appeared for place of living (beta = 5.43, SE = 1.27, p < 0.001) and negative association for age (beta = -0.16, SE = 0.03, p < 0.001) while for MCS for number of years in monasticism (beta = 0.07, SE = 0.06, p = 0.023) and sense of coherence (beta = 0.47, SE = 0.06, p < 0.001). The results indicated that monks had better mental health but worse physical health compared to the general Greek male population. More studies are required to validate the above findings

A phase i trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer

HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2-4 doses of activated NK cells from two relative donors. Donor's CD56+ cells were cultured for 20-23 days with interleukin-15 (IL-15) and hydrocortisone (HC) and administered intravenously between chemotherapy cycles. Premedication with corticosteroids and/or H1 inhibitors was allowed. Sixteen patients (performance status 0-1) with adenocarcinoma (n = 13) or squamous cell carcinoma (n = 3) at stage IIIb (n = 5) or IV (n = 11) receiving 1st (n = 13) or 2nd (n = 3) line treatment were enrolled. Fifteen patients received 2-4 doses of allogeneic activated NK cells (0.2-29 × 10 6/kg/dose, median 4.15 × 106/kg/dose). No side effects (local or systemic) were observed. At a median 22-month follow-up (range, 16.5-26 months) 2 patients with partial response and 6 patients with disease stabilization were recorded. Median progression free survival and overall survival were 5.5 and 15 months, respectively. A 56% 1-year survival and a 19% 2-year survival were recorded. In conclusion, repetitive infusions of allogeneic, in vitro activated and expanded with IL-15/HC NK cells, in combination with chemotherapy are safe and potentially clinically effective. © 2010 Springer-Verlag

Immunotherapeutic and immunoregulatory drugs in haematologic malignancies

A better understanding of the biology and pathogenesis of hematological malignancies has led to the development of immunotherapeutic and immunoregulatory drugs. Many of these agents have revolutionized the current treatment modalities, while others are under investigation. Rituximab (anti-CD20 antibody) has been established as the gold standard of treatment for aggressive B-cell lymphomas in combination with CHOP and has shown significant activity as monotherapy in the treatment of indolent B-cell lymphomas. In follicular lymphomas the combination of Rituximab with chemotherapy improves the outcome compared to chemotherapy alone. CD 20-based radioimmunotherapy, with the advantage of the bystander effect, represents an additional therapeutic alternative in B-cell lymphomas and may produce tumor regression in Rituximab resistant patients. The anti-CD52 monoclonal antibody, alemtuzumab, further expands the armamentarium against lymphoid malignancies producing high response rates in these entities. Antibody-targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33 antibody combined to calicheamicin, has shown efficacy in the treatment of refractory acute myeloid leukemia; exact indications, timing and dosing schedule for optimized efficacy remain to be determined. Interferons have proven significant activity in cutaneous lymphomas, hairy cell leukemia and chronic myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic cells microenvironment and lead to disease control in multiple myeloma as well as in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor, displays significant anti-tumor activity, especially in multiple myeloma and lymphoproliferative disorders. The addition of these agents in therapeutic regimens has improved considerably the treatment of hematological malignancies. © 2006 Bentham Science Publishers Ltd