Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway.

Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit­8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylin­eosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcription­quantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786­O and ACHN) than the effect on normal renal tubular epithelial cell (HK­2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dose­dependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.

Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities.

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor-brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.

One-Pot Synthesis of Ag/Quaternary Ammonium Salt Co-Decorated Mesoporous Silica Nanoparticles for Synergistic Treatment of Cancer and Bacterial Infections.

Developing drug delivery nanosystems with both anticancer and antibacterial effects is of great clinical value. Herein, we report a facile approach to synthesize Ag and quaternary ammonium salt (QAS) co-decorated mesoporous silica nanoparticles (MSNs), namely, Ag/QAS-MSNs, for synergistic treatment of cancer and bacterial infections. In vitro studies demonstrated that Ag/QAS-MSNs not only had a strong antibacterial activity against the bacterial pathogens but also could efficiently induce cancer cell death through an apoptotic pathway. Moreover, in vivo combination therapy with Ag and QAS in Ag/QAS-MSNs was also tested in a nude mouse tumor model, and a significant synergistic anticancer effect, which is superior to that obtained by therapy with Ag-MSNs or QAS-MSNs alone, was achieved. Such excellent anticancer and antibacterial activity of Ag/QAS-MSNs could be attributed to the synergistic effect of Ag ions and QAS. Thus, Ag/QAS-MSNs have a promising future as potent anticancer agents with high antibacterial performance.