In-vivo studies of targeted and localized cancer drug release from microporous poly-di-methyl-siloxane (PDMS) devices for the treatment of triple negative breast cancer.

Triple-negative breast cancer (TNBC) treatment is challenging and frequently characterized by an aggressive phenotype and low prognosis in comparison to other subtypes. This paper presents fabricated implantable drug-loaded microporous poly-di-methyl-siloxane (PDMS) devices for the delivery of targeted therapeutic agents [Luteinizing Hormone-Releasing Hormone conjugated paclitaxel (PTX-LHRH) and Luteinizing Hormone-Releasing Hormone conjugated prodigiosin (PG-LHRH)] for the treatment and possible prevention of triple-negative cancer recurrence. In vitro assessment using the Alamar blue assay demonstrated a significant reduction (p < 0.05) in percentage of cell growth in a time-dependent manner in the groups treated with PG, PG-LHRH, PTX, and PTX-LHRH. Subcutaneous triple-negative xenograft breast tumors were then induced in athymic female nude mice that were four weeks old. Two weeks later, the tumors were surgically but partially removed, and the device implanted. Mice were observed for tumor regrowth and organ toxicity. The animal study revealed that there was no tumor regrowth, six weeks post-treatment, when the LHRH targeted drugs (LHRH-PTX and LHRH-PGS) were used for the treatment. The possible cytotoxic effects of the released drugs on the liver, kidney, and lung are assessed using quantitative biochemical assay from blood samples of the treatment groups. Ex vivo histopathological results from organ tissues showed that the targeted cancer drugs released from the implantable drug-loaded device did not induce any adverse effect on the liver, kidneys, or lungs, based on the results of qualitative toxicity studies. The implications of the results are discussed for the targeted and localized treatment of triple negative breast cancer.

Hypothyroxinemia in acquired immune deficiency syndrome (AIDS).

Serum thyroxine (T4) and thyroid stimulating hormone (TSH) were studied in 38 patients confirmed to be infected with HIV-1 virus and the results compared with values observed in age matched healthy subjects. The mean serum total T4 in the majority of the patients, 103 +/- 32 nmol/L, was similar to values observed in the controls, 102 +/- 21 nmol/L, p > 0.05. However, 22.2 pc of the HIV-1 infected patients had total serum T4 values that were significantly lower than values in the controls, 36 +/- 12 nmol/L, p < 0.001. Since hypothyroxinemia has been associated with increased mortality in critical illness, we suggest that assessment of thyroid function may be helpful in the management of some patients with AIDS.