Cancer is a serious threat to human life and health .Therefore, there is an emergent need to develop novel anti-cancer agents with new structural type , new mechanism of action and higher efficacy .Natural products had played a key role in the dis-covery of anticancer agents .The anti-cancer activity , mechanism of action , structure and activity relationship of several lead-com-pounds which were derived from natural products were summarized in this review .

Objective To evaluate the difference in coronary microcirculation and short term prognosis in patients with different collateral circulation and underwent elective percutaneous coronary intervention ( PCI) with complete occlusion of coronary artery. Methods The study included 42 patients who had been admitted in our hospital for NSTEMI or STEMI between 01/2012 to 12/2015 without receiving revascularization treatment and whose symptoms persisted for over 6 months. According to the results of coronary angiography and the Rentrop grade, the patients were divided into 2 groups: poor collateral circulation formation group (group A, Rentrop=0 -1, n=17) and well established collateral circulation group (group B, Rentrop=2-3, n=25). The basic clinical data and the result of coronary angiography were compared. A pressure-temperature sensor wire was used to measure index of mierocirculatory resistance ( IMR) immediately after PCI. An echocardiograph was used to measure left ventricular end systolic diameter ( LVEDd) and left ventricular ejection fraction ( LVEF) postoperatively and again at 3 months after operation to evaluate the changes in cardiac function. Results The IMR value of group A was significantly higher than group B (P﹤0. 05), the grade of collateral circulation had negative correlation with IMR value (r=-0. 671, P﹤0. 05). The mean changes in LVEDd in 3 months in group B was -0. 28 mm, while in group A was 5. 76 mm (P﹤0. 05). The mean changes in LVEF in 3 mouths in group B was 5. 36% and in group A was -3. 82% (P﹤0. 05). The grading of coronary collateral circulation had negative correlation with the changes of LVEDd in 3 months (r= -0. 669, P﹤0. 05), but had positive correlation with the changes of LVEF (r=0. 657, P ﹤0. 05). The IMR value had positive correlation with the changes of LVEDd in 3 months (r=0. 686, P﹤0. 05), but had negative correlation with the changes of the LVEF (r= -0. 664, P﹤ 0. 05 ) . Conclusions Patients with poor collateral circulation was more prone to coronary microcirculatory injury than patients with good collateral circulation. Patients with good collateral circulation and microcirculation had better prognosis after the revascularization of the infarction-related vessel.

Objective To explore the clinical treatment effect of gastrointestinal tumor surgery. Methods Eighty patients with gastrointestinal tumor treated in our hospital from May 2010 to December 2014 were selected and evenly divided into the observation group (n=40) and the control group (n=40). The observation group was given laparoscopic surgery treatment while the control group was given conventional laparotomic surgery treatment. The treatment effects, recurrence situation, second surgery situation, quality of life scores and other indicators of the two groups were com-pared. Results The treatment effect of the observation group was significantly higher than that of the control group(P<0.05). The recurrence rate, second surgery and healing situation of the the observation group was also significantly higher than the control group(P<0.05). The qualify of life score of the observation group was significantly better than that of the control group, with significant difference(P<0.05). Conclusion In the treatment of patients with gastrointestinal tumor, the application of laparoscopic surgery treatment can effectively improve the treatment effect, reduce the sec-ondary damage to patients and enable total resection of hidden tumors, which improves the patients' health degree as well as their quality of life.

Objective To screen small molecule inhibitors of Fusobacterium nucleatum （Fn） based on commercially available compound libraries, and investigate their anti-colorectal cancer activities under Fn intervention in order to obtain novel anti-colorectal cancer lead compounds. Methods The promotion of colorectal cancer proliferation on organoid was validated by Fn. Secondly, the effects of anti-Fn compounds on their in vitro anticancer activity under Fn’s co-incubation with colorectal cancer HCT116 cell were comparative investigated. Finally, in vivo anticancer efficacy of highly active compounds on nude mouse colon cancer HCT116 transplanted tumor under the intervention of Fn was evaluated by gavage. Results Fn could significantly promote the proliferation of rectal cancer organoids. 9 anti-Fn active compounds could significantly enhance their in vitro anticancer activity under Fn’s co-incubation with HCT116 cells. Methotrexate had the strongest anti-cancer activity with IC₅₀ as 0.03 μmol/L. The combined use of methotrexate (0.5 mg/kg) and PD-1 (5.0 mg/kg) had a stronger anti-tumor effect than their standalone use. Conclusion As new small molecule inhibitor of Fn, methotrexate exhibited good in vitro and in vivo anti-colorectal cancer activity against HCT116 cells and nude mouse xenografts under Fn intervention, which showed the foundation for subsequent structural optimization, and could be expected to expand the new indications of methotrexate.

Natural product evodiamine and its derivatives represent a promising class of multi-target antitumor agents. However, the clinical development of these compounds has been hampered by a poor understanding of their antitumor mechanisms. To tackle this obstacle, herein, novel fluorescent probes were designed to elucidate the antitumor mode of action of 10-hydroxyevodiamine. This compound was proven to be distributed in the mitochondria and lysosomes and to act by autophagy and apoptosis mechanisms.

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent and antitumor potency. Particularly, compound was orally active and possessed excellent antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, .) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.

The dose-related adverse effects of MDM2‒P53 inhibitors have caused significant concern in the development of clinical safe anticancer agents. Herein we report an unprecedented homo-PROTAC strategy for more effective disruption of MDM2‒P53 interaction. The design concept is inspired by the capacity of sub-stoichiometric catalytic PROTACs enabling to degrade an unwanted protein and the dual functions of MDM2 as an E3 ubiquitin ligase and a binding protein with tumor suppressor P53. The new homo-PROTACs are designed to induce self-degradation of MDM2. The results of the investigation have shown that PROTAC

Nicotinamide phosphoribosyl transferase (NAMPT) is considered as a promising target for cancer therapy given its critical engagement in cancer metabolism and inflammation. However, therapeutic benefit of NAMPT enzymatic inhibitors appears very limited, likely due to the failure to intervene non-enzymatic functions of NAMPT. Herein, we show that NAMPT dampens antitumor immunity by promoting the expansion of tumor infiltrating myeloid derived suppressive cells (MDSCs) via a mechanism independent of its enzymatic activity. Using proteolysis-targeting chimera (PROTAC) technology, PROTAC A7 is identified as a potent and selective degrader of NAMPT, which degrades intracellular NAMPT (iNAMPT) via the ubiquitin-proteasome system, and in turn decreases the secretion of extracellular NAMPT (eNAMPT), the major player of the non-enzymatic activity of NAMPT. In vivo, PROTAC A7 efficiently degrades NAMPT, inhibits tumor infiltrating MDSCs, and boosts antitumor efficacy. Of note, the anticancer activity of PROTAC A7 is superior to NAMPT enzymatic inhibitors that fail to achieve the same impact on MDSCs. Together, our findings uncover the new role of enzymatically-independent function of NAMPT in remodeling the immunosuppressive tumor microenvironment, and reports the first NAMPT PROTAC A7 that is able to block the pro-tumor function of both iNAMPT and eNAMPT, pointing out a new direction for the development of NAMPT-targeted therapies.

OBJECTIVETo evaluate the photodynamic therapy (PDT) against multi-antibiotic-resistant Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S.epidermidis) obtained from patients with chronic rhinosinusitis (CRS).

METHODSForty-five CRS patients who had been given medical treatment but still needed endoscopic surgery were included in this study. The mucus from middle meatus was collected from these patients during surgery, followed by separation of S. aureus and S. epidermidis and drug sensitive test. The strains which could form biofilm were selected. Light emitting diode (LED) array with a major wavelength of (633±10) nm was used as light source and 5-Aminolevulinic acid (ALA) was used as photosensitizer in this PDT experiment. The safe range of LED dose and ALA concentration which were not toxic to bacteria by themselves were confirmed, and then did PDT experiment on S. aureus and S. epidermidis. The data of bacterial colony forming unit were transformed to lgCFU before statistical analysis.The Graph Pad Prism 5 software was used to analyzed the data.

RESULTSThirteen S. aureus and 16 S. epidermidis were included in this experiment(from 45 patients), all of them were multi-antibiotic-resistant bacteria, and four of S. aureus and five of S. epidermidis could form biofilm in each group. In planktonic S. aureus experiment, the mean lgCFU was 8.32±0.31 in control group whereas the experiment group was 6.47±0.67 (t=9.01, P<0.01), and in planktonic S. epidermidis experiment the final data was 8.34±0.20 (control group) and 6.97±0.59 (experiment group) (t=8.84, P<0.01). In biofilm S. aureus experiment, the mean lgCFU was 8.68±0.05 (control group), 6.90±0.96(experiment group) (t=3.68, P<0.05); and in biofilm S. epidermidis experiment the data was 8.67±0.05 (control group), 7.29±0.61 (experiment group, t=5.07, P<0.01).

CONCLUSIONOur results demonstrated that ALA-mediated PDT on multi-antibiotic-resistant S. aureus and S. epidermidis from CRS patients was effective in vitro. Additional work defining if the PDT treatment would damage the nasal mucosa and further checking the effectiveness of PDT in vivo is still needed.

Aminolevulinic Acid ; therapeutic use ; Anti-Bacterial Agents ; Biofilms ; Drug Resistance, Multiple, Bacterial ; Humans ; Light ; Photochemotherapy ; Photosensitizing Agents ; therapeutic use ; Rhinitis ; drug therapy ; microbiology ; Sinusitis ; drug therapy ; microbiology ; Staphylococcal Infections ; complications ; drug therapy ; Staphylococcus