Objective To investigate the efficacy of twice irradiating with focused ultrasound on recurrent and metastasized U14 cervical cancer implanted in the legs of mice. Methods Seventy-two mice with U14 cervical cancer cells implanted in their legs were divided into three groups randomly,with 24 rats in each group.One group received a single dose of focused ultrasound,while mice in the second group were irradiated twice and surgery resection was administered to the third group 7 or 8 days after the tumor was implanted.After 23 days post implantation of the tumor,local tumor recurrence and metastasis to the lungs and lymph nodes were evaluated. Results The inhibition rate after double irradiation was 61.70％ for local recurrence and 68.18％ for metastasis,significantly higher than in the other two groups. Conclusions Both single and double irradiation with focused ultrasound are effective for inhibiting local recurrence and metastasis,but double irradiation is more effective.

AIMTo look for new heart or kidney imaging agents. Five new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetyl glycine) isovalericamide (MVG2), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] isovalericamide (MVGT), 2-N-(2'-s-tri-phenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] isovalericamide (MVGH), 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-butylacetaminde)] phenyl propamide (MPGT) and 2-N-(2'-s-triphenylmethylacetyl) amino-[N'-acetyl-(N"-cyclohexanylacetaminde)] phenylpropamide (MPGH) were synthesized as primitive materials to explore the synthetic methods of polypeptides.

METHODS AND RESULTSAll target chelators were identified on the basis of the spectroscopic data, such as IR, 1HNMR, 13CNMR and elementary analysis. Different active esters with mercaptoacetic acid as primitive materials were used to explore the biodistribution of Technetium-99m labelling chelators in mice. The chelators were labeled with Technetium-99m and further tested for the biological activity in mice. Values given in ID which is the percentage injected dose per organ was tested to explore new heart imaging agents. The ID was determined in vivo by biodistribution study. Tc-99m complexes 0.1 mL was injected into laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 minutes post-injection, rats were sacrificed by decapitation, bled from the neck and the organs were removed. The radioactivities in various organs were determined in an automatic twin crystal gamma counter. Five new target chelators were labeled with Technetium-99m in high yield (> 95%). The bio-distribution resulted in mice indicate that 99Tcm-MVG2 has high kidney uptake, good retention, quick blood clearance and high activity ratios of kidneys to other tissues. 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT have better heart accumulation, but shorter retention, slower blood clearance and lower activity ratios of kidneys to other tissues. They were mainly metabolized through liver and kidney.

CONCLUSION99Tcm-MVG2 will be a new potential renal function imaging agent and 99Tcm-MVGT, 99Tcm-MVGH and 99Tcm-MPGT will be new potential heart function imaging agents if their structure and activity relationships are further studied.

Animals ; Chelating Agents ; chemical synthesis ; pharmacokinetics ; Kidney ; metabolism ; Mice ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Technetium ; pharmacokinetics ; Tissue Distribution

AIMTo explore the synthetic methods of polypeptides containing new heart of kidney imaging agents.

METHODS AND RESULTSFive new target chelators--2-N-(2'-s-triphenylmethylacetyl) amino-(N'-2"-N",N"-diethylethylamine) phenylpropamide (MPNE), 2-N-(2'-s-triphenylmethyl acetyl) amino-(N'-2"-N",N"-dimethylethylamine) phenylpropamide (MPNM), 2-N-(2's-triphenylmethylacetyl) amino-3-methyl-(N'-2"-N",N"-dimethylethylamine) butyramide (MVNM), 2-N-(2'-s-triphenyl methylacetyl) amino-3-methyl-(N'-2"-N",N"-diethylethylamine) butyramide (MVNE), 2-N-(2'-s-triphenylmethylacetyl) amino-(N'-acetylglycine) phenylpropamide (MPG2)--were synthesized through five steps with mercaptoacetic acid as primitive materials, all of which were identified on the basis of spectroscopic data, such as IR, 1HNMR, MS or elementary analysis. The protection of the mercapto group was improved and the relatively new reaction condition of active ester with amino acid is developed. All the chelators were labeled with Technetium-99m and their biological activities in mice given in ID values was tested to explore new heart imaging agents, where ID is the percentage injected dose per organ. The ID was determined by in vivo biodistribution study. Tc-99m complexes 0.1 mL was injected into the laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 min post-injection, rats were sacrificed by decapitation, bled from the neck and dissected. Organs were removed at dissection. The radioactivities in various organs were determined in an automatic twin crystal gamma counter.

CONCLUSIONThe bio-distribution results in mice indicate that 99Tcm-MVNM have higher heart uptake (ID = 8.40%/g, 2 min post-injection) and quicker blood clearance (ID = 4.3%/g, 60 min post-injection); 99Tcm-MPNE and 99Tcm-MPNM also have fairly high heart uptake and quick blood clearance; 99Tcm-MPG2 has better kidney accumulation and higher activity ratios of kidney to blood (about 4).

Amides ; chemical synthesis ; pharmacokinetics ; Animals ; Kidney ; metabolism ; Mice ; Molecular Structure ; Myocardium ; metabolism ; Organotechnetium Compounds ; chemical synthesis ; pharmacokinetics ; Peptides ; chemical synthesis ; chemistry ; pharmacokinetics ; Sulfides ; chemical synthesis ; pharmacokinetics ; Tissue Distribution

The effects of a non-selective inhibitor of cyclo-oxygenase (COX) indomethacin, and exogenous prostaglandin E(2) (PGE(2)) on A(delta) units and C units in the saphenous nerve of diabetic hyperalgesic rats were studied. The results showed that the conduction velocity of A(delta) units and C units and their mechanical threshold in diabetic hyperalgesic rats were obviously decreased, and a small number of A(delta) units (4/24) and C units (2/18) produced increased spontaneous activities. Intraperitoneal injection of indomethacin in diabetic hyperalgesic rats significantly relieved mechanical hyperalgesia, and resulted in a decrease in spontaneous afferent activities of the A(delta) units and C units. Subcutaneous injection of exogenous PGE(2) into the diabetic hyperalgesic and control rats produced a significant decrease in mechanical threshold of the A(delta) units and C units, and elicited discharge from 3 A(delta) units (3/24) and 1 C unit (1/18) in diabetic hyperalgesic rats and from 2 A(delta) units (2/13) in control rats. The present data suggest that the synthesis and release of PGs are increased in diabetic neuropathy, PGs can sensitize and /or activate A(delta) units and C units and elicit hyperalgesia and allodynia in diabetic rats.
Afferent Pathways ; drug effects ; physiopathology ; Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Femoral Nerve ; drug effects ; physiopathology ; Hyperalgesia ; physiopathology ; Indomethacin ; pharmacology ; Male ; Pain Threshold ; drug effects ; Prostaglandin Antagonists ; pharmacology ; Rats ; Rats, Sprague-Dawley

Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 20 months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.
Adenocarcinoma ; diagnostic imaging ; drug therapy ; pathology ; secondary ; Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; Catheter Ablation ; Cetuximab ; Cytokine-Induced Killer Cells ; immunology ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Drug Delivery Systems ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Immunotherapy, Adoptive ; Liver Neoplasms ; secondary ; surgery ; Lung Neoplasms ; secondary ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Multimodal Imaging ; Neoplasm Staging ; Positron-Emission Tomography ; Quality of Life ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Sigmoid Neoplasms ; diagnostic imaging ; drug therapy ; pathology ; Tomography, X-Ray Computed

Antitubercular Agents ; pharmacology ; Codon ; genetics ; Drug Resistance, Bacterial ; Ethambutol ; pharmacology ; Genes, Bacterial ; Mutation ; Mycobacterium tuberculosis ; drug effects ; genetics ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA