The International Bathymetric Chart of the Southern Ocean Version 2.

The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60°S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50°S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50°S.

An Open-Label Study of the Safety and Efficacy of Tag-7 Gene-Modified Tumor Cells-Based Vaccine in Patients with Locally Advanced or Metastatic Malignant Melanoma or Renal Cell Cancer.

LESSONS LEARNED: This study showed that carefully selected patients with locally advanced and metastatic forms of malignant melanoma and renal cell carcinoma could potentially have long-term disease control with a tag-7 gene-modified tumor cells-based vaccine. Randomized clinical trials in patients whose tumors produce low amounts of immunosuppressive factors are needed to confirm this hypothesis in both the adjuvant and metastatic settings. BACKGROUND: Immunotherapy may produce long-lasting effects on survival and toxicity. The magnitude of efficacy may be dependent on immune factors. We analyzed the results of a phase I/II study of a tag-7 gene-modified tumor cells-based vaccine (GMV) in patients with malignant melanoma (MM) or renal cell carcinoma (RCC) with biomarker analysis of immunosuppressive factors (ISFs) production by their tumor cells. METHODS: From 2001 to 2014, 80 patients received GMV: 68 with MM and 12 with RCC. Treatment in the metastatic setting included 61 patients (MM, 51; RCC, 10), and treatment in the adjuvant setting (after complete cytoreduction) included 19 patients (MM, 17; RCC, 2). Twenty-six patients were stage III (33%), and 54 (67%) were stage IV. The patients' tumor samples were transferred to culture, transfected with tag-7 gene, and inactivated by radiation. The produced product was injected subcutaneously every 3 weeks until progression or 2 years of therapy. ISFs were measured in the supernatants of the tumor cell cultures and used as predictive factors. RESULTS: No major safety issues or grade 5 adverse events (AEs) were seen. One grade 4 and two grade 3 AEs were registered. No AEs were registered in 89.4% of treatment cycles. No delayed AE was found. The 5-year overall survival (OS) in the intention-to-treat population was 25.1%. There were no differences between MM OS and RCC OS (log rank, p = .44). Median OS in the metastatic setting was 0.7 years and in the adjuvant setting was 3.1 years. Classification trees were built on the basis of ISF production (Fig. 1). The median OS was 6.6 years in the favorable prognosis (FP) group (major histocompatibility complex class I polypeptide-related sequence A [MICA] level ≤582 pg/mL, n = 15) and 4.6 months in the unfavorable (UF) group (MICA level >582 pg/mL, n = 12; p < .0001). No significant differences were found between classification trees based on ISFs (transforming growth factor ß1 [TGF-ß1], interleukin-10 [IL-10], and vascular endothelial growth factor [VEGF]). In patients with stage III-IV MM with FP, median OS was 2.3 years, with 31% patients alive at 10 years (Fig. 2) in the UF group (0.4 years; log rank, p = 1.94E-5). No FP patients received modern immunotherapy. CONCLUSION: GMV showed high results in carefully selected patients with low ISF (TGF-ß1, IL-10, and VEGF) production. The method should be further investigated in patients with FP.

Methylation of the BIN1 gene promoter CpG island associated with breast and prostate cancer.

BACKGROUND: Loss of BIN1 tumor suppressor expression is abundant in human cancer and its frequency exceeds that of genetic alterations, suggesting the role of epigenetic regulators (DNA methylation). BIN1 re-expression in the DU145 prostate cancer cell line after 5-aza-2'-deoxycytidine treatment was recently reported but no methylation of the BIN1 promoter CpG island was found in DU145. METHODS: Methylation-sensitive arbitrarily-primed PCR was used to detect genomic loci abnormally methylated in breast cancer. BIN1 CpG island fragment was identified among the differentially methylated loci as a result of direct sequencing of the methylation-sensitive arbitrarily-primed PCR product and subsequent BLAST alliance. BIN1 CpG island cancer related methylation in breast and prostate cancers was confirmed by bisulphite sequencing and its methylation frequency was evaluated by methylation sensitive PCR. Loss of heterozygosity analysis of the BIN1 region was performed with two introgenic and one closely adjacent extragenic microsatellite markers.BIN1 expression was evaluated by real-time RT-PCR. RESULTS: We have identified a 3'-part of BIN1 promoter CpG island among the genomic loci abnormally methylated in breast cancer. The fragment proved to be methylated in 18/99 (18%) and 4/46 (9%) breast and prostate tumors, correspondingly, as well as in MCF7 and T47D breast cancer cell lines, but was never methylated in normal tissues and lymphocytes as well as in DU145 and LNCaP prostate cancer cell lines. The 5'-part of the CpG island revealed no methylation in all samples tested. BIN1 expression losses were detected in MCF7 and T47D cells and were characteristic of primary breast tumors (10/13; 77%), while loss of heterozygosity was a rare event in tissue samples (2/22 informative cases; 9%) and was ruled out for MCF7. CONCLUSION: BIN1 promoter CpG island is composed of two parts differing drastically in the methylation patterns in cancer. This appears to be a common feature of cancer related genes and demands further functional significance exploration. Although we have found no evidence of the functional role of such a non-core methylation in BIN1 expression regulation, our data do not altogether rule this possibility out.

Binding of alpha2-macroglobulin to collagen type I: modification of collagen matrix by alpha2-macroglobulin induces the enhancement of macrophage migration.

Alpha2-macroglobulin (a2M) secreted by tissue macrophages and fibroblasts functions in the environment of extracellular matrix macromolecules. We supposed that it may interact with these molecules and change the properties of extracellular matrix. Modified variant of ELISA was used to prove the direct binding of human a2M to collagen. Native and transformed by plasmin a2M, as well as plasmin, used as the control, were labeled by biotin. It has been found that the transformed, but not the native a2M form binds to type I collagen molecules: K(d)=(1.168 +/- 1.14) x 10(-11) M. The data obtained give a strong evidence of high power of the interaction between a2M and type I collagen: practically no reverse dissociation may be seen for such a binding. The modification of three-dimensional collagen matrix by binding to the transformed a2M resulted in the enhancement of migration of macrophages, carrying the receptors for a2M, but not splenocytes that lack for such receptors. Our results allow to suggest that a2M may be one of the components of extracellular matrix, and may change the properties of microenvironment for immunocompetent cells during the processes of inflammation, reparation and tumor invasion.