Mechanistic advancement in chemotherapeutic agents modulated antitumor immune response / 药学学报

Chemotherapeutic agents, also known as cytotoxic anticancer agents, inhibit the cancer cell proliferation via interrupting DNA replication, transcription and microtubule stability etc. Chemotherapeutic agents have been used in clinical cancer treatment for decades. Recently, with the tremendous advancement in immuno-oncology, chemotherapeutic agents have aroused renewed interest for their great potential to sensitize tumor cells to immunotherapy. Meanwhile, it is worth noting that the effects of chemotherapeutic agents on the immune system involve multiple aspects with complex mechanisms. Currently, there still lacks guidance for the combined use of chemotherapy and immunotherapy, and the clinical benefits remain obscure, impelling a better understanding of the impact of chemotherapeutic agents on the antitumor immunity. This article reviews the mechanistic insights into chemotherapy-modulated antitumor immune responses, with major focus on the direct effect on immune cells and the immunogenic remodeling of tumor cells. The review is particularly interested in the chemotherapy-trigged signaling that contributes to the immunogenic cell death. This review may provide useful insights into the immunomodulatory effects of chemotherapeutic agents and the implications in exploring therapeutic opportunities of chemotherapy in cancer immunotherapy.

Recent progress in the study on antitumor drugs targeting hypoxia-inducible factor-1 / 药学学报

Hypoxia-inducible factor-1 (HIF-1), as a transcription factor, plays an important role in the adaptation to hypoxic microenvironment within tumors. It can induce a series of genes transcription that participate in angiogenesis, glucose metabolism, cell proliferation, and cell migration/invasion. Thus HIF-1 not only allows cancer cells to survive in hypoxic microenvironment, but also makes the tumor more aggressive. Moreover, HIF-1 also induces tumors to acquire resistance to chemo-/radio-therapy, and is related to poor prognosis. HIF-1 emerges gradually as a potential target to develop new antitumor drugs. This paper reviews recent progress in this field.

Studies on sLe~(a/x) and Hematogenous Metastasis of Cancer / 中国生物工程杂志

The expression of sLea/x which correlates with conventional histopathologic parameters serves as a useful indicator for the prognosis of metastatic disease. The bindings between sLea/x and their common ligand E-selectin initiate hematogenous metastasis of cancer. Certain bioactive conformation is crucial for the interaction between sLea/x and their ligands. Thus, a new class of compounds that mimic the structures of sLea/x can potently inhibit not only their functional bindings to selectins, but also the metastasis of cancer. This review is mainly on the sLea/x molecular structure,biosynthesis,distribution, especially the relationship between sLea/x and hematogenous metastasis of cancer and the design of drugs that mimic the structures of sLea/x.

Effect of sulfated polymannuroguluronate on Tat induced proinflammatory cytokines release in THP-1 cells and its mechanism of action / 药学学报

<p><b>AIM</b>To investigate the effects of sulfated polymannuroguluronate (SPMG), a novel candidate anti-AIDS drug in Phase II clinical trial, on Tat-induced release of proinflammatory cytokines (i.e., TNFalpha, IL-1beta and IL-6) and its related mechanism.</p><p><b>METHODS</b>The effects of SPMG on Tat induced TNFalpha (4 h), IL-1beta and IL-6 (6 h) secretion in THP-1 cells were measured by ELISA. Western blotting analysis was used to study the effects of SPMG on Tat induced PKCzeta, PKCtheta and PKCsigma phosphorylation.</p><p><b>RESULTS</b>SPMG (50 to 100 microg x mL(-1)) markedly suppressed TNFalpha, IL-1beta and IL-6 secretion in Tat activated THP-1 cells. In THP-1 cells the phosphorylation levels of PKCzeta, PKCtheta and PKCsigma significantly increased following Tat stimulation, and only PKCsigma phosphorylation levels was inhibited by SPMG (50 to 100 microg x mL(-1)).</p><p><b>CONCLUSION</b>SPMG suppresses the secretion of proinflammatory cytokines in THP-1 cells may be by inhibiting PKCsigma activation.</p>

Effects of acidic oligose on differentially expressed genes in the mice model of Alzheimer's disease by microarray / 药学学报

<p><b>AIM</b>To investigate the molecular mechanism of protective effect of acidic oligose 971 on Alzheimer's disease mouse model by using microarray.</p><p><b>METHODS</b>Balb/c mice were randomly divided into control group, beta-AP(25-35) i.c.v. injected group and 971-treated group. The learning-memory ability of mice was tested by Morris water maze experiment. Total RNA of the cerebral cortex was extracted from the mice of each group. cDNA microarrays containing 1176 genes were used to investigate the gene expression pattern of each group. Expressions of 5 genes were randomly selected for further confirmation by RT-PCR.</p><p><b>RESULTS</b>Icv injection of beta-AP(25-35) caused significant impairments in spatial and working memory performances of mice in Morris water maze and which were relieved by the treatment of 971. Up- and down- regulated genes were 19 and 12 in beta-AP(25-35)-injected group vs control group, respectively. Up- and down- regulated genes were 13 and 4, respectively, in 971-treated group vs beta-AP(25-35)-injected group. RT-PCR results indicated that 5 genes showed identical results to that of the microarray.</p><p><b>CONCLUSION</b>The protective effect of 971 on learning and memory ability of beta-AP(25-35)-treated mouse may be related to the expression changes of genes involved in cell cycle, DNA repair, nerve growth, synaptic plasticity and immune response, etc.</p>