Managing major depressive disorder in adolescents in primary care.

ABSTRACT: Major depressive disorder (MDD) remains a significant risk to adolescent health and well-being, recently amplified by the COVID-19 pandemic. Access to adolescent mental health care services remains challenging in many areas, resulting in many adolescents diagnosed with MDD remaining untreated. Primary care providers are becoming increasingly crucial in promptly diagnosing and treating this concern. Various clinical guidelines can support clinicians in developing strategies for screening, diagnosing, and managing a vulnerable population with MDD. Standardized screenings, algorithms, and treatment guidelines can help improve the quality of life and functional impairment of those with MDD.

Treatment of squamous carcinoma in mice with a vaccine enriched for cells that induce immunity to squamous carcinoma--a new vaccination strategy.

We report a new vaccination strategy for squamous cell carcinoma (SCC). The vaccine was prepared by transfer of unfractionated DNA-fragments (25 kb) from squamous carcinoma cells (KLN205, DBA/2 origin (H-2(d))) into LM mouse fibroblasts (C3H/He origin; H-2(k)), a highly immunogenic cell line. To enhance their nonspecific immunogenic properties, the fibroblasts were modified before DNA transfer to secrete IL-2 and to express additional allogeneic MHC class I determinants. As the transferred DNA integrates into the genome of the recipient cells, and is replicated as the cells divide, sufficient DNA to prepare the vaccine could be obtained from as few as 10(7) squamous carcinoma cells (4 mm tumor). Since only a small proportion of the transfected cell-population was expected to have incorporated genes specifying antigens associated with the squamous carcinoma cells (TAA), we devised a novel approach to enrich the vaccine for cells that induce immunity to the SCC. Aliquots of the transfected population were divided into 10 small pools (initial inoculums = 1 x 10(3)). We reasoned that if the starting inoculums were sufficiently small, then the distribution of highly immunogenic and weakly immunogenic cells in each pool would not be the same. Cells from individual pools were allowed to increase in number. A portion of the expanded cell populations were maintained frozen/viable for later recovery. The remaining portions were used to immunize naïve DBA/2 mice. Pools containing greater numbers of immunogenic cells were identified by 2 independent assays. Frozen aliquots of cells from the pool that stimulated immunity to the squamous carcinoma to the greatest extent were recovered and subdivided for additional rounds of immune selection. Enhanced immunity to squamous carcinoma mediated by CD8+ T cells was induced in tumor-bearing mice treated solely by immunization with the enriched cell-population.

Combined therapy of an established, highly aggressive breast cancer in mice with paclitaxel and a unique DNA-based cell vaccine.

Here, we describe the enhanced benefits of treating a highly aggressive breast cancer in mice with a combination of paclitaxel and immunization with a unique DNA-based cell vaccine. An adenocarcinoma was isolated from a spontaneous neoplasm that arose in the mammary gland of a C3H/He mouse (H-2(k)) (SB5b cells). The vaccine was prepared by transfer of genomic DNA-fragments (25 kb) from the breast cancer cells into a mouse fibroblast cell line (LM), modified to enhance its immunogenic properties. As the transferred DNA is integrated, and replicated as the recipient cells divide, the vaccine could be prepared from relatively small numbers of cancer cells (10(7) = 4 mm tumor). SB5b cells were injected into the mammary fat pad of naïve C3H/He mice, which are highly susceptible to the growth of the cancer cells. When the tumors reached 3 mm, the mice were injected s.c. with a noncurative dose of paclitaxel. Six days later, when immune competence returned, the mice received the first of 3 weekly s.c. injections of the vaccine. The combined therapy induced robust cellular immunity to the breast cancer, mediated by CD8+ and NK/LAK cells, which resulted in prolonged survival. The immunity was specific, as immunization with a vaccine prepared by transfer of DNA from B16 melanoma cells into the fibroblasts failed to induce immunity to the breast cancer. This type of vaccine raises the possibility that an analogous strategy could be used in the treatment of breast cancer patients at an early stage of the disease.

Immunity to squamous carcinoma in mice immunized with dendritic cells transfected with genomic DNA from squamous carcinoma cells.

Immunotherapy of squamous cell carcinoma (SCC) at an early stage of the disease increases the likelihood of success. We report a new vaccination strategy designed to prepare SCC vaccines from microgram amounts of tumor tissue, enabling the treatment of patients with minimal residual disease. The vaccine was prepared by transfer of sheared genomic DNA-fragments (25 kb) from KLN205 cells, an SCC cell line of DBA/2 mouse origin, into syngeneic bone marrow-derived mature dendritic cells (DCs). More than 90% of the transfected DCs took up DNA from the neoplasm and transferred genes were expressed as protein. The DCs expressed CD11c, CD11b, and the costimulatory molecules CD40, CD80 and CD86, characteristic of mature DCs. Syngeneic DBA/2J mice, highly susceptible to the growth of KLN205 cells, were injected intravenously (i.v.) with the transfected DCs, followed by a subcutaneous (s.c.) injection of the tumor cells. The strong immunogenic properties of the transfected cells were indicated by the finding that the survival of the tumor-bearing mice was prolonged (P<.001), relative to that of mice in various control groups. Enzyme-linked immuno spot (ELISPOT IFN-gamma) assays revealed the activation of cell-mediated immunity directed toward the SCC in mice immunized with the transfected DCs. Two independent in vitro cytotoxicity assays indicated the presence of robust cell-mediated immunity directed toward the SCC in mice immunized with the transfected cells.