Molecular target-based cancer therapy is playing a more and more important role in cancer therapy because of its high specificity, good tolerance and so on. There are different kinds of molecular targeted drugs such as monoclonal antibodies and small molecular kinase inhibitors, and more than 50 drugs have been approved since 1997. When the first monoclonal antibody, rituximab, was on the market. The development of molecular target-based cancer therapeutics has become the main approach. Based on this, we summarized the drugs approved by FDA and introduced their mechanism of actions and clinical applications. In order to incorporate most molecular targeted drugs and describe clearly various characteristics, we divided them into four categories: drugs related to EGFR, drugs related to antiangiogenesis, drugs related to specific antigen and other targeted drugs. The purpose of this review is to provide a current status of this field and discover the main problems in the molecular targeted therapy.
Angiogenesis Inhibitors ; Antibodies, Monoclonal ; Drug Delivery Systems ; Humans ; Molecular Targeted Therapy ; Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

OBJECTIVE: To observe the effects of hypericin on proliferation, apoptosis of leukemia cells and its possible mechanism. METHODS: Subcellular localization of hypericin in leukemia cells by fluorescence microscopy. MTT(3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test was adopted to observe the inhibitory effects of hypericin on the proliferation of leukemia cells and calculated its half maximal inhibitory concentration(IC50). The technology of flow cytometry, Annexin-V-FITC/PI double stained method were employed to measure the cell apoptosis of leukemia cells after hypericin treatment. RESULTS: The optimal time for hypericin to entry into cells was 16 h. Hypericin could inhibit the proliferation of leukemia cells in vitro, and the inhibition presented obvious dose-effect relationship(r=0.990 5, P<0.01). The apoptotic ratio of leukemia cells was gradually increased. The ratio of Bax/Bcl-2 was significantly increased, and the apoptotic protein caspase-3, 8, 9 is cleaved and activated. CONCLUSION: Hypericin could inhibit the growth of leukemia cells, induce the apoptosis through induction of caspase dependent apoptosis pathway.

Compared with normal tissues and cells, the tumor microenvironment has significant differences. For example, glutathione-related metabolic enzymes and reactive oxygen species are highly expressed in different subcellular structures, resulting in an unbalanced redox state. Aiming at the specific redox state in tumor tissues and cells, a series of small molecule prodrug self-assembled nanoparticles can be designed and connected by intelligent response linkers including disulfide bonds, sulfide bonds, and selenium bonds, thioketal bonds, etc. The in vitro and in vivo efficiency and metabolic mode of these nanoparticles are related to the type of linker. This review will summarize the tumor redox microenvironment, the design of intelligent responsive small molecule prodrug nanoparticles, and the metabolic pathways of small molecule prodrug nanoparticles with different connecting linkers and their relationship with drug efficacy.

BACKGROUND: Renin-angiotensin-aldosterone system existed in bone tissue. Recent studies on antihypertensive drugs found that angiotensin converting enzyme inhibitor type antihypertensive drug was possibly effective for osteoporosis. Perindopril is one of the commonly used antihypertensive drugs. Whether perindopril affected bone metabolism or could be used in anti-osteoporosis has not been reported.
OBJECTIVE: To observe effects of perindopril on bone metabolism in a rat model of osteoporosis induced by retinoic acid.
METHODS: Fifty Sprague-Dawley rats were randomly divided into five groups, with ten in each group. In the model group and each perindopril groups, rats were intragastricaly administered retinoic acid solution 80 mg/kg per day. After successful model establishment, rats in different perindopril groups were intragastrical y administered perindopril 2, 4 and 8 mg/kg per day, once a day, for 42 consecutive days. In the normal control and model groups, rats were given an equal volume of distil ed water. Serum calcium, phosphorus, alkaline phosphatase, bone mass and bone mineral density were detected in each group. Expression of bone specific alkaline phosphatase and tartrate-resistant acid phosphatase mRNA in bone tissue was determined.
RESULTS AND CONCLUSION: Compared with the model group, after treatment with perindopril, serum calcium and phosphorus levels were increased, alkaline phosphatase activities were significantly decreased, bone mass and bone mineral density were obviously increased in rats with retinoic acid-induced osteoporosis. Expression of bone specific alkaline phosphatase mRNA was higher in the perindopril 8 mg/kg group than in the perindopril 2 and 4 mg/kg groups and model group. Tartrate-resistant acid phosphatase mRNA expression was higher in the perindopril 8 mg/kg group than in the model group. These results indicated that perindopril could improve partial bone metabolic biochemical markers in osteoporosis rats, promoted bone formation by up-regulating bone specific alkaline phosphatase mRNA expression, and had a certain preventive effect on retinoic acid-induced osteoporosis.

Objective The aim of this study was to assess the value of △Np63α in predicting tumor recurrence after curative resection in esophageal squamous cell carcinoma (ESCC) patients.Methods We analyzed △Np63α protein cxpression in 304 clinicopathologically characterized ESCC cases by immunohistochemistry.Results We found △Np63α expression was positive in 122 (40％) of 304 cases.△Np63α expression was higher in the cancer tissue than in non-tumorous control tissue at protein level(P =0.034).There was a significant difference of △Np63α expression in patients categorized according to invasive depth (P =0.001),tumor position (P =0.001) and lymph nodes metastasis condition (P =0.001).Multivariate analyses showed that △Np63α was an independent prognostic marker for ESCC recurrence.Conclusion △Np63α is associated with outcome of ESCC and can be a novel predictor for poor prognosis of ESCC patients after curative resection.

AIM:To investigate the effect and the mechanism of Zhibai Dihuang Pill(Radix Rehmanniae praeparata,Fructus Corni,Rhizoma Dioscoreae,Rhizoma Anemarrhenae,Cortex phellodendri Chinensis,etc.) on patients with hyperthyroidism. METHODS: Eighty-five hyperthyroid patients were randomly divided into two groups.The control group(40 cases) were treated with propylthiouracil,while the treatment group(45 cases) were treated with propylthiouracil and Zhibai Dihuang Pill;in the 12-week long treatment period,the heart rate,body weight,thyroid free FT_3、FT_4 and TSH and the serum level of FAA,resistin,adiponectin,leptin of patients in both groups were measured. RESULTS: After treatment,the heart rate,the serum of FT_3,FT_4 decreased and the body weight,TSH increased in both groups(P0.05).(CONCLUSION): Zhibai Dihuang Pill can improve the abnormal metabolism of sugar and fat in patients with hyperthyroidism by its actions on the serum level of FFA,resistin,adiponectin,leptin.

Objective: To study the antipyretic action of Dipseudoephedrine Glycyrrhizin and its effect on heart rate and blood pressure of rats.Methods: The model of pyretic rabbit was established by diphtheria-pertussis-tetanus triple vaccine,and to observe the effect of Dipseudoephedrine Glycyrrhizin on temperature of rabbit. Two-path physiological recorder was used to measure heart rate and blood pressure.Results: The experiment proved that Dipseudoephedrine Glycyrrhizin can decrease the anus temperature of pyretic rabbit obviously.Dipseudoephedrine Glycyrrhizanate had no remarkably effect on heart rate and blood pressure.Conclusion: Dipseudoephedrine Glycyrrhizin has antipyretic action and has no effect on heart rate and blood pressure within studied dose.

Objective To explore the diagnostic value of LUNX gene to marrow micrometastases of lung cancer.Methods To detect LUNX mRNA of marrow samples of 51 patients of lung cancer,4 patients of breast cancer,6 patients of lymphadenoma,3 patients of liver cancer and 22 patients of benign disease by real-time RT-PCR.Results The positive detection rate and meso-copies of lung cancer were 58.8% (30/51) and 35copies/ml respectively.The positive detection rate and meso-copies of other diseases were all 0,The positive detection rate and meso-copies of lung cancer was significantly higher than that of patients with other diseases (x~2=11.12,U_c=3.7329,P

0.05).②blood test and gastrointestinal reaction of the two groups one month after operation:The leukocytopenia(

Objective To explore the psychomotor development in 12 month old infants born after in vitro fertilization with a control group of infants concieved naturally.Methods A matched control study was performed on psychomotor development of 12-month-old infants concieved with use of assisted reproductive technology(in vitro fertilization only).The control group was matched according to maternal age,parity,social class and level of parental education.The suitable mothers were invited to participate at the 28th week of gestation and were followed up to delivery.The infants of the two groups were followed up to 12 months old and a formal developmental assessment was done with the Children Development Center of China(CDCC) scales of infant development.Results The incidences of preterm birth,low birth weight and twin pregnancy were significantly higher in the assisted conception group.No statistically significant difference was found in the mental development index and psychomotor development index between assisted conception and control groups.Conclusions The levels of psychomotor development in 12 months old infants born after in vitro fertilization are normal.But as the incidences of preterm birth,low birth weight and multifetation are significantly higher in vitro fertilization group,it need to follow up the ongoing development of these children.