A metastasizing mouse cell line (TS/A), originated from a mammary adenocarcinoma which arose spontaneously in a BALB/c female retired breeder, has been established in vitro. It displayed a remarkable morphologic heterogeneity, which is evident in plastic adherent cultures (cell types ranging from epithelial-like to fibroblast-like) as well as in semi-solid agar cultures. The TS/A line exhibited the presence of specific cytoplasmic estradiol receptor, with a binding activity of 16 fmoles/mg cytosol protein. The in vivo growth pattern was as follows: a s.c. inoculum of 105 cells caused a 100 per cent tumor take and kill in syngeneic animals; mean survival time was 54 +/- 1 days; it did not show significant transplant immunogenicity in syngeneic animals; it was able to give rise to both spontaneous lung metastases and artificial lung colonies; it had a high capacity to grow in H-2 matched, minor histocompatibility antigen incompatible hosts (10(6) cells killed 100 per cent DBA/2 mice in 58 +/- 2 days). This line of spontaneous mammary tumor cells is proposed as a useful model for studies on the heterogeneity of the neoplastic population in relation to metastatic spread, on tumor immunogenicity, and on therapy of mammary neoplasia.

The relationship between major histocompatibility complex (MHC) antigens and metastasis was investigated on B16 melanoma variants. B16 cell lines express low amounts of murine MHC (H-2) antigens. A high expression can be induced in line B16-A by in vitro treatment with immune interferon (IFN-gamma) or by in vivo transplant in allogeneic mice. The increase of H-2 antigens correlated with an enhancement of lung colonization in young syngeneic mice. The higher metastatic capacity of B16-A cells with induced high levels of H-2 antigens was observed also in adult mice and in young mice pretreated with cyclophosphamide. These results were confirmed investigating the behaviour of a mutant B16 clone (B78H1) which was selectively resistant to the H-2-inducing action of IFN-gamma: lung colonization ability was not increased by IFN pretreatment. The study of variants derived from individual B16-A lung colonies revealed a wide range of H-2 levels. Variants with a low expression had a low colonization ability; one out of two variants with a high H-2 expression also was poorly colonizing. IFN-gamma-mediated H-2 expression appeared to act as an enhancer, rather than a determinant of B16 metastatic capacity.

Summary The RMZ cell line was established from a bone marrow metastasis of a human alveolar rhabdomyosarcoma. Since the beginning of the in vitro culture, RMZ cells showed a differentiation-related morphological heterogeneity: actively proliferating polygonal or spindle-shaped cells were observed along with a few multinucleated myotube-like structures and giant cells, frequently multinucleated. All these cell types were still present after over 40 passages. A set of clonal derivatives has been obtained from the second in vitro subculture. All the clones showed the same morphological heterogeneity of the parental cells, but differed from one another in the degree of differentiation.Multinucleated myotube-like structures were strongly stained by anti-desmin antibody; most mononuclear cells were weakly stained. About 80% of RMZ and cloned cells were scored as desmin-positive in cytocentrifuged preparations. The expression of embryonic myosin heavy chain, specifically recognized by the monoclonal antibody BF-G6, was found in RMZ cell line and was localised in the myotube-like structures. Only a few giant cells and rare mononucleated polygonal cells were stained. The average proportion of BF-G6 positive cells in cytocentrifuged preparations was of about 6% of the total RMZ cells. In the two RMZ clones studied, the expression of embryonic myosin was correlated to the proportion of myotube-like structures: a BF-G6 positivity of 35% was found in the most differentiated one.

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This paper analyzes the impact of the Belt and Road Initiative on Europe with a specific\ud focus on Italy. We concentrate on the impact of new railways and port infrastructures on\ud bilateral trade. Our analysis suggests that the development of new railway connections\ud will benefit most of the Northern and Central European countries. Some industries like\ud automotive and electronics that have a higher value to weight ratio will benefit more\ud than others. However, due to higher costs, railway services will never reach a high\ud percentage of total import/export flows. Investment in new port facilities, although less\ud “new” compared with railways, may be a bigger game changer. The development of\ud the Port of Piraeus has already increased the importance of the Mediterranean Sea as\ud an import/export hub for China. If the other planned investments in Egypt and Algeria\ud are completed, this phenomenon will be magnified. This presents a huge challenge for\ud Italy. The Italian port in the high Adriatic Sea could be displaced by Piraeus capacity,\ud especially if this port is linked through railways with the center of Europe. Italy needs\ud to coordinate its ports together with its railway network to take advantage of Belt and\ud Road Initiative opportunities

SUMMARY We studied the expression of H‐2b alloantigens in three different B16 melanoma lines cultured in vitro, Cell lines were B16‐F1 and two cell cultures (named B16‐A and B16‐B) newly derived from two different in vivo sublines of B16 melanoma. The assays used were in vivo tumour growth in allogeneic (BALB/c and B10.BR) as compared to syngeneic mice, in vitro cell‐mediated cytotoxicity by anti‐H‐2b immune lymphocytes and absorption of anti‐H‐2b antisera activity. The B16‐F1 line was able to efficiently kill allogeneic hosts, could not be lysed by anti‐H‐2b cytotoxic effectors and did not express any serologically detectable amount of H‐2b alloantigens. The B16‐A line was H‐2 positive during the early in vitro passages, then, at the 8th–10th passages, it acquired the capacity to kill allogeneic hosts, lost the sensitivity to anti‐H‐2b cytotoxic effectors and the H‐2Kb antigens became undetectable. The expression of H‐2Db was reduced, although at a lower degree. Similar data were obtained with B 16‐B cells, which after 10 in vitro passages grew and killed allogeneic hosts, showed a decreased sensitivity to cytotoxic anti‐H‐2b effectors and a very low expression of the K region antigens. The results indicate that H‐2 expression is altered in B 16 melanoma lines and this may influence the different metastatic capacity of such cells.

China's unprecedented growth largely results from industrial development having critically sustained the country's economic transition after 1978. As common to the developmental context, catching-up capabilities have been both absorbed from external sources and generated by indigenous activities. These also represent exogenous and endogenous seeds of innovative activities respectively. The relative emphasis on the two has evolved over progressive industrialization-transition stages in China, leading the country to grow a global manufacturing hub. The volume and quality of innovative activities has however resulted unevenly distributed at a local level. Literature considers embeddedness, in particular, as one of the key features in the development of the local innovative environment. This paper investigates if the mixes of seeds may have delayed the innovative activities to gain embeddedness along their diffusion in the Chinese prefectural cities. In a great deal of stylization and methodological design, innovative activities are here approximated by the applications to the European Patent Office from China collected in the OECD REGPAT database as originally rearranged by the applicant's and inventor's prefectural locations. These locations are taken to build three indicators to be combined in a clustering procedure set to measure separate levels of embeddedness. The results suggest a growing diffusion and embeddedness of the innovative activities in the Chinese prefectural cities since the early-2000s, despite they remain highly concentrated in some regions, that is, mainly those having historically hosted the Special Economic Zones where more exogenous seeds appear to have actually delayed the innovative activities to gain embeddedness.

The metastatic TS/A line has been recently derived from a spontaneous BALB/c mammary tumor. When TS/A cells were cultured in 0.33 per cent agar, two morphologically distinct types of colonies were observed from which two sets of clones were obtained. E clones were derived from small, transparent colonies, whereas F clones were from large, thick, actively growing colonies. All the clones were tumorigenic in syngeneic BALB/c females. However, E clones showed higher ability than F clones to metastasize spontaneously to the lung. Comparison between E and F clones shows that the high level of spontaneous metastasization to the lung is associated with epithelial-like in vitro growth pattern, spontaneous dome formation and growth pattern in 0.33 per cent agar cultures. The ability to give rise to lung colonies following intravenous inoculation is not a predictive parameter for the spontaneous metastatic potential.