Host defense peptide LL-37 is involved in the regulation of cell proliferation and production of pro-inflammatory cytokines in hepatocellular carcinoma cells.

Recent studies on the roles and mechanisms of LL-37 have demonstrated that LL-37 can either serve as a tumor promoter or a tumor suppressor in different cancers. The expression and function of LL-37 in hepatocellular carcinoma (HCC), however, remain unclear. In the present study, we confirmed the down-regulation of LL-37 in HCC tissues and the synthetic LL-37 peptide reduced the viability of HCC cells in a dose-dependent manner. Furthermore, we demonstrated that LL-37 peptide significantly delayed G1-S transition in Huh7 but not in HepG2 cells by suppressing CyclinD1-CDK4-p21 checkpoint signaling pathway. However, LL-37 caused no obvious apoptosis both in Huh7 and HepG2 cells, though the expression of apoptosis-related genes was strongly changed through qRT-PCR analysis, hinting at the possibility that LL-37 participates in regulating the apoptosis of HCC cells, but may not the only mechanism. Besides, we also identified that LL-37 treatment strongly inhibited the mRNA expression of TLR4 both in Huh7 and HepG2 cells, accompanied with the reduced expression of genes responsible for pro-inflammatory cytokines, including IL-8 and IL-6. In conclusion, our research suggested that LL-37 may be associated with the development of HCC.

Drug release and solubility properties of two zeolitic metal-organic frameworks influenced by their hydrophobicity/hydrophilicity.

Metal-organic frameworks (MOFs) have shown significant potential for drug delivery applications. However, there remains a scarcity of comprehensive research addressing the influence of surface properties of MOFs on drug release kinetics and drug solubility. This study focuses on examining the influence of MOFs hydrophilicity and hydrophobicity on the controlled release and solubility of drugs. To achieve this, we prepared drug-loaded nanoparticles through in situ synthesis and created a drug-MOF co-amorphous system using the ball milling technique. Under neutral conditions, the hydrophilic MOF-based drug delivery system demonstrated a comparatively slower drug release profile than its hydrophobic counterpart. This observation suggests that the hydrophilic system holds promise in mitigating drug side effects by enabling improved control over drug release. The implementation of hydrophobic MOFs in co-amorphous systems yields a more pronounced effect on enhancing solubility compared to hydrophilic MOFs. This study offers valuable insights for achieving optimal drug release kinetics and solubility by delicately manipulating surface properties of MOFs.

Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy in the treatment of locally advanced cervical carcinoma: An updated meta-analysis based on randomized controlled trials.

BACKGROUND: Radiotherapy concurrent with cisplatin is the standard regimen used for treatment of locally advanced cervical carcinoma. In this meta-analysis, survival, recurrence, compliance, and acute adverse effects were compared between weekly and triweekly cisplatin-based concurrent chemoradiotherapy regimens for treatment of cervical cancer. METHODS: A systematic search for relevant studies was conducted using PubMed, Cochrane Library, EMBASE, and Medline databases. Fixed- or random-effects models were used for pooled analysis. The endpoints were overall survival, recurrence, compliance, and acute adverse effects reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Eight randomized controlled trials met the inclusion criteria. No significant differences were observed between the 2 arms with respect to recurrence, survival, and acute adverse effects (all P > .05). However, the triweekly cisplatin regimen was associated with significantly lower incidence of local recurrence (OR, 1.72; 95% CI, 1.07-2.78; P = .03), radiotherapy completion (OR, 2.08; 95% CI, 0.99-4.38; P = .05), and anemia (OR, 2.10; 95% CI, 1.01-4.37; P = .05), while a weekly cisplatin regimen was associated with a lower risk of leukopenia (OR, 0.57; 95% CI, 0.42-0.92; P = .00) and thrombocytopenia (OR, 0.55; 95% CI, 0.31-0.97; P = .04). CONCLUSIONS: Triweekly cisplatin-based chemotherapy significantly reduced local recurrence with tolerable toxicity and might be the optimal regimen in concurrent chemoradiotherapy for locally advanced cervical carcinoma.

Targeted delivery of RGD-modified liposomes encapsulating both combretastatin A-4 and doxorubicin for tumor therapy: in vitro and in vivo studies.

Arg-Gly-Asp (RGD) modified doxorubicin-loaded liposomes could improve anticancer effect, and vascular disrupting agents (VDAs) could induce a rapid and selective shutdown of the blood vessels of tumors. We propose that RGD-modified liposomes for co-encapsulation and sequential release of vascular disrupting agent combretastatin A-4 (CA-4) and cytotoxic agent doxorubicin (Dox) could enhance tumor inhibition responses. In this study, we encapsulated Dox and CA-4 in RGD-modified liposomes. The release rate of Dox was proved to be much slower than that of CA-4 in vitro. Flow cytometry and laser confocal scanning microscopy clearly showed that RGD-modification promoted intracellular uptake of liposomal drugs by B16/B16F10 melanoma tumor cells and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay showed that the IC(50) of RGD-modified liposomes was lower than that of the corresponding unmodified liposomes. Therapeutic benefits were examined on B16F10 melanoma tumors subcutaneously growing in C57BL/6 mice. In vivo study demonstrated that RGD-modified liposomes exhibited the most pronounced tumor regression effect when both CA-4 and Dox were co-encapsulated. These results suggest that the targeted drug delivery system for co-encapsulation of vascular disrupting agents and anticancer agents may be a promising strategy for cancer treatment.