The RAS (rat sarcoma) gene is one of the important oncogenes, and its mutation is present in about 30% human tumors. KRAS (kirsten rat sarcoma viral oncogene) is one of the three RAS subtypes, and KRAS mutations are more common than the mutations in other two RAS subtypes. In recent years, with the continuous research, new ideas have been provided for the treatment of cancers via targeting-KRAS. Efforts have been made to develop various KRAS inhibitors. Here, based on the mechanism of action, we classified KRAS inhibitors into two categories: inhibitors that directly target KRAS and inhibitors that indirectly act on KRAS. The representative KRAS inhibitors were summarized and introduced in this paper.

Indoleamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme in the degradation of tryptophan to kynurenine. IDO1 is highly expressed in some tumor tissues. IDO1 can deplete tryptophan in tumor microenvironment, inhibit T cell function, and mediate the immune escape of tumor cells. Thus, IDO1 is considered a potential target of tumor immunotherapy. Currently, there are several IDO1 inhibitors in clinical research studies. The mechanism of IDO1-mediated tumor immune escape and the structure of IDO1 inhibitors are summarized in this review.

Cell Transformation, Neoplastic ; drug effects ; genetics ; Dimethyl Sulfoxide ; pharmacology ; Electroporation ; methods ; HL-60 Cells ; Humans ; Membrane Proteins ; genetics ; Neoplasm Proteins ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics ; Stromal Interaction Molecule 1 ; Transfection

This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.
Animals ; Antineoplastic Agents, Alkylating ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclophosphamide ; analogs & derivatives ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms, Experimental ; pathology ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tumor Burden ; drug effects

Human neutrophil elastase (hNE) is a serine proteolytic enzyme mainly distributed in neutrophils. When the balance between anti-hNE protein and hNE is broken, excessive release of hNE can cause the occurrence of various diseases. Therefore, inhibition of hNE is a promising therapeutic strategy. In this paper, the structure, action mechanism, physiological function of hNE and the development of hNE inhibitors were briefly summarized, in order to provide information for the related research.

The focus of microbiologists has moved to the rare actinomycetes.For selective isolation of rare actinomycetes that all play the important role in bioactive compounds,the approaches which involve the methods using gellan gum and flooding solution、 rehydration-centrifugation(RC)、 extremely high frequency radiation(EHF)、 bacteriophage and sucrose-gradient centrifugation were introduced in this paper.

Colectomy ; Colonic Neoplasms/surgery* ; Colonoscopy ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Robotic Surgical Procedures

OBJECTIVENeonatal respiratory failure (RF) is a serious clinical problem associated with high mortality. This study aimed to investigate the incidence and outcome of neonatal RF in the Children's Hospital of Hebei Province.

METHODSThe medical data of 304 RF infants who were admitted to the neonatal intensive care unit (NICU) of the Children's Hospital of Hebei Province between March 2004 and February 2005 were prospectively studied.

RESULTSThe incidence of RF was 35.7% in the NICU during the 12-month period. Respiratory distress syndrome (28.4%), amniotic fluid aspiration syndrome (22.9%), and pneumonia (14.7%) were leading diseases resulting in RF. Of the 304 patients, 17 (5.6%) died of RF, 96 (31.6%) discontinued therapy on account of various causes and 191 (62.8%) recovered or improved. The mean length of hospital stay was 14.9+/-7.1 days and the mean medical cost was 7977+/-3 426 CNY for the 191 survivors.

CONCLUSIONSThe morbidity, mortality and medical costs of neonatal RF are high in Hebei Province. It is essential to improve the quality in respiratory therapy and perinatal care in order to reduce the morbidity and mortality related to high-risk pregnancies.

Adult ; China ; epidemiology ; Female ; Hospital Costs ; Humans ; Incidence ; Infant, Newborn ; Male ; Pregnancy ; Prospective Studies ; Respiratory Insufficiency ; epidemiology ; mortality

Objective · To analyze the clinical distribution and drug resistance of Acinetobacter junii (A. junii) and Acinetobacter lwoffii (A. lwoffii) from a grade 3A hospital in Shanghai, China, and provide the foundation for prevention and control of infections caused by them. Methods · A. junii and A. lwoffii were collected from the hospital between Aug, 2011 and Aug, 2016. VITEK2 Compact of bioMérieux (French) was used for bacterial identification and antibiotic susceptibility tests, clinical information of each strain was also analyzed. Results · 28 strains of A. junii and 58 strains of A. lwoffii were enrolled. A. junii was mainly from the departments of urology, thoracic surgery and geriatrics, and the samples were mainly sputum and urine. The resistant rates of A. junii to gentamicin, ampicillin sulbactam, piperacillin, piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, levofloxacin, ciprofloxacin and cotrimoxazole were 35.71%, 3.57%, 10.71%, 3.57%, 3.57%, 3.57%, 3.57%, 3.57%, 0, 3.57% and 35.71%, respectively. A. lwoffii was mainly isolated from the departments of urology, geriatrics, respiratory and renal medicine, and the samples mainly included urine, blood and sputum. The rates of antibiotics (mentioned above) resistance were 29.31%, 13.79%, 13.79%, 6.90%, 20.69%, 18.97%, 12.07%, 15.52%, 18.97%, 31.03% and 31.03%, respectively. The levels of antibiotic resistance of these two strains were constant during the five years. Conclusion · A. junii and A. lwoffii antibiotic resistant rates were much lower than those of reported A. baumannii, the over-all antibiotic resistances of A. junii were lower than those of A. lwoffii. This study provided fundamental data for prevention or control of these two strains by empirical use of antibiotics.

Objective To explore the feasibility of constructing tissue engineered porcine corneal stroma with skin fibroblasts in vivo.Methods Skin fibroblasts were isolated from embryonic porcine,cultured and expanded in vitro.Cells were labeled with green fluorescence protein(GFP) gene by retro-viral infection.Cells at passage 3 were seeded on polyglycolic acid(PGA) non-woven fibers to form a cell-scaffold complex.The complexes were then implanted into porcines' corneal stroma after culturing in vitro for 1 week.Engineered stroma was observed continuously and harvested after 8 weeks for gross and histological evaluation.PGA with corneal stromal cells was served as control. Results The engineered tissue in the stroma gradually became transparent over a period of 8 weeks,showing no difference with the control group.Histologically,the engineered stromal lamellar was relatively regular and similar to the control.The implanted cells were confirmed by GFP expression under fluorescent microscope.By transmission electron microscopy examination, no significant difference in the diameter of collagen fiber was observed between the engineered stroma and normal stroma. Conclusion Tissue engineered corneal stroma may be formed with skin fibroblasts in porcine corneal microenvironment.