Initial insights into the interaction of antibodies radiolabeled with Lutetium-177 and Actinium-225 with tumor microenvironment in experimental human and canine osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a prevalent primary bone cancer affecting both humans and canines. This study describes initial insights into the interaction of the human monoclonal antibody IF3 to an insulin-like growth factor 2 receptor (IGF2R) radiolabeled with either alpha-emitting Actinium-225 (225Ac) or beta-emitting Lutetium-177 (177Lu) radionuclides with the OS cells and tumor microenvironment (TME) in experimental human and canine OS. BASIC PROCEDURES: SCID mice bearing canine Gracie or human OS-33 OS tumors were treated with 177Lu- or 225Ac-labeled IF3 antibody, sacrificed at 24, 72 or 168 h post-treatment and their tumors were analyzed by immunohistochemistry (IHC) for the presence of OS cells, various elements of TME as well as for the double DNA strand breaks with γH2AX and caspase 3 assays. MAIN FINDINGS: IHC revealed a reduction in IGF2R-positive OS cells and OS stem cell populations post therapy with 225Ac- and 177Lu-labeled IF3 antibody. Notably, radiolabeled IF3 antibody effectively diminished pro-tumorigenic M2 macrophages, highlighting its therapeutic promise. The study also unveiled varied responses of natural killer (NK) cells and M1 macrophages, shedding light on the intricate TME interplay. Time-dependent increase in γ-H2AX staining in canine Gracie and human OS-33 tumors treated with [177Lu]Lu-IF3 and [225Ac]Ac-IF3 was observed at 24 and 72 h post-RIT. PRINCIPAL CONCLUSIONS: These findings suggest that radiolabeled antibodies offer a hopeful avenue for personalized OS treatment, emphasizing the importance of understanding their impact on the TME and potential synergies with immunotherapy.

Optic vesicle morphogenesis requires primary cilia.

Arl13b is a gene known to regulate ciliogenesis. Functional alterations in this gene's activity have been associated with Joubert syndrome. We found that in Arl13 null mouse embryos the orientation of the optic cup is inverted, such that the lens is abnormally surrounded by an inverted optic cup whose retina pigmented epithelium is oddly facing the surface ectoderm. Loss of Arl13b leads to the disruption of optic vesicle's patterning and expansion of ventral fates. We show that this phenotype is consequence of miss-regulation of Sonic hedgehog (Shh) signaling and demonstrate that the Arl13b-/- eye phenotype can be rescued by deletion of Gli2, a downstream effector of the Shh pathway. This work identified an unexpected role of primary cilia during the morphogenetic movements required for the formation of the eye.

Characterization of Tunneling Nanotubes in Wharton's jelly Mesenchymal Stem Cells. An Intercellular Exchange of Components between Neighboring Cells.

Intercellular communication is one of the most important events in cell population behavior. In the last decade, tunneling nanotubes (TNTs) have been recognized as a new form of long distance intercellular connection. TNT function is to allow molecular and subcellular structure exchange between neighboring cells via the transfer of molecules and organelles such as calcium ions, prions, viral and bacterial pathogens, small lysosomes and mitochondria. New findings support the concept that mesenchymal stem cells (MSCs) can affect cell microenvironment by the release of soluble factors or the transfer of cellular components to neighboring cells, in a way which significantly contributes to cell regulation and tissue repair, although the underlying mechanisms remain poorly understood. MSCs have many advantages for their implementation in regenerative medicine. The TNTs in these cell types are heterogeneous in both structure and function, probably due to their highly dynamic behavior. In this work we report an extensive and detailed description of types, structure, components, dynamics and functionality of the TNTs bridging neighboring human umbilical cord MSCs obtained from Wharton"s jelly. Characterization studies were carried out through phase contrast, fluorescence, electron microscopy and time lapse images with the aim of describing cells suitable for an eventual regenerative medicine.

[Using Twitter in oncology. Research, continuing education, and advocacy]. / L'uso di Twitter in oncologia. Ricerca, aggiornamento e advocacy.

Traditional mass media coverage has been enhanced by Twitter, an interactive, real-time media, useful in health care, and particularly in oncology. Social media such as Twitter are gaining increasing acceptance as tools for instantaneous scientific dialogue. Professional medical societies such as ASCO and ESMO are using microblogging to expand the reach of scientific communications at and around their scientific meetings. To widen the message and maximize the potential for word-of-mouth marketing using Twitter, organizations (such as AIOM, ASCO or ESMO) and industries need a strategic communications plan to ensure on-going social media conversations. Twitter is a very powerful tool indeed that amplifies the results of scientific meetings, and conference organisers should put in place strategies to capitalise on this. This review demonstrates that cancer patients also share information more and more via Twitter about their disease, including diagnosis, symptoms, and treatments. This information could prove useful to health care providers.

[Cancer on the big screen. How and when movies deal with oncological diseases]. / Il cancro sul grande schermo. Quanto, come e quando il cinema si occupa delle malattie oncologiche.

Films that feature characters with cancer have become a familiar sight for movie-goers. 148 movies treating tumors were selected, produced all over the world since the Thirties, in which cancer had "prompt", "relevant", or "plot" character. In order to clearly understand each film's peculiar message about cancer, we recollected data such as genealogy, year and country of production, main characters' age and gender, and kind of tumor. Movies deal with cancer through very relevant questions, as well as themes and contexts that have great influence on oncologist's mind and consciousness. Specially in recent years, films have tackled some of the most important issues around cancer, such as his epidemiology and environmental causes; the economic implications of therapies; the management of symptoms and side effects; the psychological dynamics; the care toward the ending of life. The most frequent treatment mentioned in the movies was chemotherapy followed by antalgic therapy. Very often the ill person on the screen doesn't get over the disease and his death is somehow useful to the plot's outcome. This pattern is so strongly standardized that it persists in spite of real progress of treatments. Movies use disease, and other tragedies, as a dramatic device, and since drama is what we expect of the medium, should we be concerned that there is a gap between fiction and reality? Movies represent an essential step of educational process, but their potential has been fully exploited only in recent times. By watching movies on cancer, oncologists could become more conscious of problems they are already facing in the therapeutic setting: cancer and sexuality, the relationship between the ill person and the medical staff, side effects of therapies. Some films simply make us reflect upon the meaning of life and death. This is useful for the sharing of cancer care, from personal or familiar problems to issues of collective relevance.