Virus-based cancer vaccines are nowadays considered an interesting approach in the field of cancer immunotherapy, despite the observation that the majority of the immune responses they elicit are against the virus and not against the tumor. In contrast, targeting tumor associated antigens is effective, however the identification of these antigens remains challenging. Here, we describe ExtraCRAd, a multi-vaccination strategy focused on an oncolytic virus artificially wrapped with tumor cancer membranes carrying tumor antigens. We demonstrate that ExtraCRAd displays increased infectivity and oncolytic effect in vitro and in vivo. We show that this nanoparticle platform controls the growth of aggressive melanoma and lung tumors in vivo both in preventive and therapeutic setting, creating a highly specific anti-cancer immune response. In conclusion, ExtraCRAd might serve as the next generation of personalized cancer vaccines with enhanced features over standard vaccination regimens, representing an alternative way to target cancer.
Cancer immunotherapy has revolutionized the way tumors are treated. Nevertheless, efficient and robust testing platforms are still missing, including clinically relevant human ex vivo tumor assays that allow pre-treatment testing of cancer therapies and selection of the most efficient and safe therapy for a specific patient. In the case of immunotherapy, this testing platform would require not only cancer cells but also the tumor microenvironment, including immune cells. Here we discuss the applications of patient-derived tumor organoid cultures and the possibilities in using complex Research.
Background: Middle Eastern women worldwide increasingly seek aesthetic treatment to enhance their beauty and improve self-esteem, but literature describing standards of beauty across the Middle East are scarce. Knowledge of facial anthropometry and Middle Eastern subregional beauty preferences and aesthetic weaknesses are key to develop an effective facial enhancement strategy that does not jeopardize ethnic identity or facial harmony. Methods: Dermatologists and plastic surgeons from 8 Middle Eastern countries who had 7.5–25 (mean 13.5) years of experience in aesthetic medicine examined female Middle Eastern beauty in 4 geographic subregions: the Gulf (comprising Bahrain, Kuwait, Saudi Arabia, and the United Arab Emirates), Iran, Lebanon, and Egypt. They developed consensus opinions regarding facial beauty, aesthetic deficiencies, and injectable treatment solutions. Results: Facial anthropometry differs between Middle Eastern and Western women, and also within the region. Although subregional differences are seen, beauty is generally recognized by an oval or round face; temple fullness; pronounced, elevated, arched eyebrows; large almond-shaped eyes; well-defined, laterally full cheeks; a small, straight nose; full lips; a well-defined jawline; and a prominent, pointed chin. The relative prominence of the nose necessitates attention to the lips and the shape and projection of the chin. Aging is often accompanied by midface sagging that leads to increased heaviness in the lower facial third. Conclusions: Middle Eastern beauty is characterized by striking eyes, defined cheeks, and full lips. These consensus opinions inform aesthetic practitioners who treat Middle Eastern women worldwide about their aesthetic ideals and the implications for treatment.
Due to the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T cell repertoire. While CD8+ anti-tumor cytotoxic T lymphocytes (CTL) are the preferred effectors of cancer immunotherapy, CD4+ T cell help is also required for an optimal antitumor immune response to occur. Hence, we investigated whether the pathogen-related CD4+ T cell memory populations could be re-engaged to support the CTLs, converting a weak primary antitumor immune response into a stronger secondary one. To this end, we used our PeptiCRAd technology that consists of an oncolytic adenovirus coated with MHC-I-restricted tumor-specific peptides, and developed it further by introducing pathogen-specific MHC-II-restricted peptides. Mice pre-immunized with tetanus vaccine were challenged with B16.OVA tumors and treated with the newly developed hybrid TT-OVA-PeptiCRAd containing both tetanus toxoid-and tumorspecific peptides. Treatment with the hybrid PeptiCRAd significantly enhanced anti-tumor efficacy and induced TT-specific, CD40 ligand-expressing CD4+ T helper cells and maturation of antigen presenting cells (APCs). Importantly, this approach could be extended to naturally occurring tumor peptides (both tumor-associated antigens and neoantigens), as well as to other pathogens beyond tetanus, highlighting the usefulness of this technique to take full advantage of CD4+ memory T cell repertoires when designing immunotherapeutic treatment regimens. Finally, the anti-tumor effect was even more prominent when combined with the immune checkpoint inhibitor anti-PD1, strengthening the rationale behind combination therapy with oncolytic viruses. Research.
Hemoptysis is an occasional complication of adult pulmonary disease and is rare in children. The most common causes in adults are infection, bronchiectasis, pulmonary neoplasm, cystic fibrosis, pulmonary infarct, and trauma; in children the most common causes are infection and congenital abnormalities of the cardiopulmonary vasculature. Nine cases of hemoptysis in seven infants and two children will be presented. Two cases were fatal, thus illustrating the importance of rapid and definitive therapy early in the course. One of the fatal cases is the first case report in the otolaryngological literature of fatal hemoptysis in the newborn as a result of vascular anomalies associated with an absent left pulmonary artery. Eight cases of various causes, including small vessel vascular abnormality, trauma, recurrent pulmonary infection, and laryngotracheal papilloma, are discussed. The literature is reviewed, embryology is discussed, and a mechanism of death is theorized for the patient with the congenital vessel anomaly. Management considerations for hemoptysis in infants and children are discussed.
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