Complement as Prognostic Biomarker and Potential Therapeutic Target in Renal Cell Carcinoma.

Preclinical studies demonstrated that complement promotes tumor growth. Therefore, we sought to determine the best target for complement-based therapy among common human malignancies. High expression of 11 complement genes was linked to unfavorable prognosis in renal cell carcinoma. Complement protein expression or deposition was observed mainly in stroma, leukocytes, and tumor vasculature, corresponding to a role of complement in regulating the tumor microenvironment. Complement abundance in tumors correlated with a high nuclear grade. Complement genes clustered within an aggressive inflammatory subtype of renal cancer characterized by poor prognosis, markers of T cell dysfunction, and alternatively activated macrophages. Plasma levels of complement proteins correlated with response to immune checkpoint inhibitors. Corroborating human data, complement deficiencies and blockade reduced tumor growth by enhancing antitumor immunity and seemingly reducing angiogenesis in a mouse model of kidney cancer resistant to PD-1 blockade. Overall, this study implicates complement in the immune landscape of renal cell carcinoma, and notwithstanding cohort size and preclinical model limitations, the data suggest that tumors resistant to immune checkpoint inhibitors might be suitable targets for complement-based therapy.

Fabrication and In-vitro Evaluation of Buccal Mucoadhesive Tablet of Meloxicam.

In this study, buccal mucoadhesive tablets of meloxicam were formulated for drug delivery as an alternative route. Direct compression method was applied for the preparation of tablets. Also, different polymers, including hydroxypropyl methyl cellulose (HPMC) 1000, 4000, and 10000, as well as carbopol 934p and carbopol 971p were used as the mucoadhesive polymer and retardant polymer. Thirteen formulations were investigated with various concentrations of polymers. The physicochemical characteristics, in-vitro drug release, swelling index, and taste modification of tablets were evaluated. Also, Carr's index and Hausner ratio were studied. In addition, zero-order, first-order, and Higuchi kinetics were investigated and the results showed that the highest correlation coefficient (R2) is related to zero-order kinetic for formulations B2 and B3. Furthermore, the highest R2 is related to Higuchi kinetic for formulation C3. Formulation B2 showed the maximum release of 99% in 12 h. The results demonstrated that Formulation B2 can be considered as a proper buccal mucoadhesive tablet of meloxicam with desired property.

Crosslinked-polyvinyl alcohol-carboxymethyl cellulose/ZnO nanocomposite fibrous mats containing erythromycin (PVA-CMC/ZnO-EM): Fabrication, characterization and in-vitro release and anti-bacterial properties.

Recently, nanocomposite nanofibers have been extensively used for biomedical applications. It is expected that simultaneous incorporation of antibiotic drugs and ZnO nanoparticles into nanofiber resulted in providing the synergistic anti-bacterial effect. The main aim of the present study is to fabricate polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)-ZnO nanocomposite fibrous mats containing erythromycin (EM) drug and crosslink them using 2% glutaraldehyde vapor and 3% AlCl3 alcoholic solution. The fabricated nanofibers characterized via TGA, FTIR, TEM, and SEM, indicating that the addition of ZnO nanoparticles and EM molecules into the fabricated nanofibers resulted in changing their average diameter. Their anti-bacterial activity was studied against S. aureus and E. coli and found that PVA-CMC/ZnO-EM nanofibers show excellent antimicrobial activity. In-vitro release profile showed that EM release from PVA-CMC/ZnO-EM nanofibers was slowly increased. Sustained drug release profile and excellent anti-bacterial activity of PVA-CMC/ZnO-EM nanofiber indicated that it was an ideal biomaterial for wound dressings.