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 investigate the clinical characteristics of adult Wilms'tumor in Chinese adults and to improve the recognition of adult Wilms'tumor.Methods The clinical data of 6 Wilms'tumor patients treated in our hospital were reviewed. Of them, there were 4 male patients and 2 female patients with mean age of 31 years old. Four patients with abdominal and flank pain and 2 patients with abdominal masses were the main clinical manifestations. One case accompanied with hematuria and another one had fever.Tumor masses were palpable by physical examination in 4 patients. Five patients had percussion tenderness over kidney region and 1 case had abdominal tenderness. Six cases underwent urinalysis and red blood cell was positive in 2 cases. There were no abnormal results in other laboratory tests. Chest X-ray was routinely performed before operation. Six patients underwent ultrasonography and all showed hypoechoic masses (5.0cm×5.0 cm-22.0 cm×25.0 cm) with clear margin. Four cases examined by CT and all had solid masses with inhomogeneous density and clear margin. On enhanced CT scan, 1 of 4 cases demonstrated irregular enhancement of the mass with local hemorrhagic necrosis area. The CT value ranged from 11-40 HU, with an average value of 22.5 HU, and increased to 35-78 HU, with an average value of 63.5 HU after administration of contrast. Two cases of MRI revealed solid mass defects.Three cases underwent IVU examination and showed the enlargement of renal umbra as well as thinning of renal calices caused by the compression of tumor and 1 case showed hydronephrosis.Thus, 5 cases were diagnosed with renal tumor and 1 case was diagnosed with cavitas pelvis tumor before operation. Five patients successfully underwent nephrectomies and 1 patient accepted oophorotomy with no subsequent complication.Retroperitoneal lymph node dissection(RPLND) was performed at the time of radical nephrectomy or oophorotomy in all patients. The tumor was found to be about 5-25 cm in size during operation. One of the tumors had invaded pancreas tail, one had invaded to the lateral abdominal wall and one had invaded into the inferior caval vein. Renal hilar lymph node was found to be exceeded 1.5 cm×1.5 cm in 2 patients. The post-operative incisal surface of the tumor presented with gray-yellow color. Capsule was intact in 4 patients. Three cases had hemorrhagic necrosis in tumor center. All the specimens sent for the pathological examination. None received adjuvant therapy before operation. Four patients received chemotherapy plus radiotherapy after surgery and other 2 patients received chemotherapy only. All patients were followed up with routine lab tests, ultrasonography and chest X-ray.Results Six patients were staged according to the National Wilms'Tumor Study staging system as follows: 1 case in stage Ⅰ, 2 cases in stageⅡ, 2 cases in stage Ⅲ and 1 case in stage Ⅳ. Nephrectomies or oophorotomy were performed in all patients successfully. Tumor diameters were from 4.5-25.0 cm, in average 11.8 cm.All cases had pathological diagnosis of Wilm's tumor. Five cases were classified into favorable histologic type and 1 case was in unfavorable histologic type. Two patients with lymph node metastasis and 3 patients with local invasion were observed. One patient with pulmonary metastasis was recorded. Six patients were followed up for 1-7 years. Five patients survived with no evidence of cancer recurrence. One patient died of pulmonary metastasis 2 years after surgery.Conclusions The majority of adult Wilms'tumors are found with local invasion and metastasis. The incidence of hematogenous metastasis in adult Wilms'tumor is higher than other types of renal tumor as well. The early diagnosis and radical surgical treatment and adjuvant chemoradiotherapy could improve the survival rate.

Objective To review the diagnosis and treatment of squamous cell carcinoma of renal pelvis. Methods The clinical data from October 1991 to May 2009 of eight cases of squamous cell carcinoma of renal pelvis were reviewed and analyzed retrospectively. The symptoms of the patients were hematuria (eight cases), pain (seven cases) and abdominal mass (one case). All patients underwent B-ultrasound and IVU examination and four cases underwent CT scan. Three cases were diagnosed as having a tumor before surgery. Five cases were diagnosed as renal calculus, two of the five cases were diagnosed by intraoperative frozen section. Radical nephroureterectomy were performed in four cases, nephrectomy in three cases and palliative resection in one case. Results Histological classification revealed that six cases were moderately differentiated, one case was well differentiated and one case was poorly differentiated. Two cases had stage pT1/pT2 and six cases had stage pT3/pT4. 2 cases had regional lymph nodes metastasis. Seven cases were followed-up. All patients died of tumor recurrence or metastasis. The median tumor specific survive time was six months (range from two months to 42 months). Conclusions Squamous cell carcinoma of renal pelvis is often occurs concurrently with urolithiasis which could lead to difficulty in diagnose before operation. As the most of the patients were diagnosed with advanced stage disease, squamous cell carcinoma of renal pelvis tended to early recurrence and metastasis and the prognosis was very poor.

Objective: To investigate the role of miR-142-3p in alleviation of house dust mite induced allergic airway inflammation among children, so as to provide insights into unraveling the pathogenesis of allergic airway inflammation. Methods: Serum samples were collected from 15 patients with house dust mite induced allergic asthma and 15 healthy children in Jiangnan University Medical Center from September to November 2022, and serum miR-142-3p expression was quantified using a fluorescent quantitative real time PCR (qPCR) assay. The levels of interleukin 6 (IL 6) and tumor necrosis factor α (TNF α) were measured in the cell culture supernatant using enzyme linked immunosorbent assay (ELISA), and the expression of high mobility group box 1 (HMGB1) was detected at transcriptional and translational lvels using qPCR and Western blotting assays. The negative regulation of the HMGB1 gene by miR 142 3p was identified using a dual luciferase gene reporter assay, and the expression of downstream regulatory proteins was determined in human normal lung epithelial cells (BEAS 2B) cells transfected with miR 142 3p using Western blotting. In addition, female C57BL/6 mice at ages of 6-8 weeks were randomly assigned to the phosphate buffer saline (PBS) group, house dust mite sensitized airway inflammation group and house dust mite sensitized airway inflammation + miR 142 3p intervention group. Mouse airway inflammation was evaluated using hematoxylin eosin staining, and the expression of inflammatory cells and inflammatory cytokines were detected in mouse bronchoalveolar lavage fluid (BALF) using Giemsa staining and ELISA. Results: Lower serum miR-142-3p expression was quantified among children with house dust mite induced allergic asthma than among healthy controls (1.33±0.21 vs. 4.74±0.62, t=5.22, P <0.05). Stimulation with dermatophagoides farinae extract (DFE) resulted in a reduction in miR-142-3p expression in BEAS-2B cells (0.82±0.25), while transfection with miR-142-3p mimics resulted in a rise in miR-142-3p expression in BEAS-2B cells (0.55±0.14)( t=3.31, 3.94, P <0.05). Pre treatment with miR-142-3p reduced the expression of IL 6(2.25±0.46)and TNF α(6.58±1.95) ( t=4.86, 3.38, P <0.05) in BEAS 2B cells stimulated with DFE, and treatment with miR-142-3p mimics resulted in a reduction in TLR4 and NF-κB expression in BEAS-2B cells via negative regulation of the HMGB1 expression. In addition, treatment with miR-142-3p was found to alleviate inflammatory cell infiltration in lung tissues of house dust mite sensitized mice, and results in a reduction in interleukin 4 (IL-4)[(107.60±10.43)pg/mL], interleukin 5 (IL 5)[(95.78±13.14)pg/mL] and HMGB1[(2.52±0.87)pg/mL] expression in BALF ( t=10.32, 7.29, 2.90, P <0.05). Conclusion miR-142-3p alleviates house dust mite induced allergic airway inflammation among children via negative regulation of the HMGB1/TLR4/NF-κB pathway.

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.

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.

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