Objective To investigate the effects of the intracellular delivery of HPV16E7_(49-57) epi- tope modified by cell-penetrating peptide HIV-Tat_(49-57) and its influential factors.Methods The unique HLA-A2+/H-2kb+ limited CTL epitope of HPV16E7 fused with a cell-penetrating sequence (HIV-Tat_(49-57)) was designed and a 18-mer peptide was synthesized with aid of polypeptide solid phase synthesis technique. The intracellular transport capabilities of these peptides were tested with indirect immunofluorescence assay and laser confocal microscopy.In addition,the CTL epitope and 18-met peptide were used to stimulate PBMC of healthy C57BL/6 mice,and the E7_(49-57) specific CTL responses were measured by LDH cytotoxicity detection kit in PBMC of those mice.Results The HIV-Tat_(49-57) peptide could efficiently assist HPV 16E7_(49-57) peptide in penetrating into BHK cells in a time and dose-dependent manner (P＜0.05).Further- more,the specific CTL activity induced by the 18-mer peptide was much stronger than that induced by the single epitope.Conclusion The results show that HIV-Tat_(49-57) can efficiently deliver the exogenous anti- genic peptide into the cytoplasm of live cells,and induce specific CTL response.This is a new way to de- sign peptide-based vaccine of HPV.

Designing of natural product-like compounds using natural products as template structures is an important strategy for the discovery of new drugs. Gambogic acid (GA), which is a Garcinia natural product with a unique caged xanthone scaffold, inhibits potent antitumor activity both in vitro and in vivo. This review summarized the researches on the identification of the antitumor pharmacophore of GA, and the design, structural optimization and structure-activity relationship (SAR) of natural product-like caged xanthones based on it.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Biological Products ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Screening Assays, Antitumor ; Garcinia ; chemistry ; Humans ; Molecular Structure ; Structure-Activity Relationship ; Xanthones ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology

This study is to analyze and identify the water soluble components of water buffalo horn (Bubali Cornu, WBH), and also establish a method for investigating these components. Shotgun proteomic analysis identified proteins in WBH aqueous extraction: keratin, collagen, desmoglein, etc. Ultrafiltration and LC-MS/MS were used to separate and identify the peptides in WBH aqueous extract, as a result, identified peptides were mainly derived from nonspecific degradation products of keratin and collagen, which including C-terminal peptides and non C-terminal peptides. Hypoxanthine, uridine, guanosine, and adenosine were identified by comparing with the standards. The strategy in present study could be used in analyzing water soluble components of animal horn derived TCM. It provides a reference for investigation of the material basis of animal horn derived TCM.
Animals ; Buffaloes ; Chromatography, Liquid ; Guanosine ; Horns ; chemistry ; Hypoxanthine ; Mass Spectrometry ; Medicine, Chinese Traditional ; Peptides ; Proteomics ; Tandem Mass Spectrometry ; Uridine

The study found that the physician-patient trust crisis results from overreliance on technology trust instead of interpersonal trust and institutional trust. The alleged “Paternalistic government innovation”in healthcare service has caused wastes of healthcare resources and gap below public expectancy due to its incompetence in resolving social problems,further eroding institutional legality and intensifying such crisis.This research aimed to identify government accountabilities in building such trust from three aspects.

Objective To investigate the influences of mutation at precore and basic core promoter(BCP) region in hepatitis B virus(HBV) on the immune response of specific cytotoxic T lymphocytes(CTL) in patients with chronic hepatitis B(CHB).Methods The number of specific CTL in peripheral blood mononuclear(PBMC) of CHB patients were tested by cytokine flow cytome- try(CFC) and HBV core18-27 peptide.HBV precore and BCP fragments were directly sequenced. Results Twenty-one(38.9%) samples were HBV precore G1896A mutation.Twenty-six(48.1%) samples were BCP region 1762/1764 combined mutation.Thirteen(24.1%) stains were three sites mutated simultaneously.Stimulated with HBV core 18-27 in vitro,the specific CTL level was signifi- cantly higher in the patients with G1896A mutation and BCP region mutation [(0.41?0.09)%, (0.36?0.08)%,(0.48?0.08)%,respectively]than those without mutation[(0.11?0.06)%, P

This study was aimed to observe bronchial asthma patients in remission after treatment of traditional Chi-nese medicine(TCM) with four diagnostic information, syndrome differentiation and changes oflung function indicators, in order to explore the efficacy evaluation with TCM characteristics. TCM tongue manifestation instrument, TCM in-quiry scale, pulse-taking instrument, acoustic diagnostic information collection system, and spirometer were used in thecollection of 33 bronchial asthma cases in remission before and after treatment (1~5 months) basedon four diagnos-tic information and lung function indexes. Single-factor analysis of variance and other methods were used in the analysis of four diagnostic parameters and lung function indexes before and after treatment. The results showed that after TCM treatment, there were significant changes on indexes such as facial complexion, tongue sub-region color, color of tongue coating and other parameters. There was significant difference in the acoustic parameters before and after treatment. After TCM treatment, the frequency of lung system symptom such as nasal obstruction was decreased. There was no significant difference on changes of pulse-taking indexes among asthma patients before and after treat-ment. After treatment, the FEV1.0% of asthma patients was increased,whichindicated that asthma ventilatory function had been improved to some extent. It was concluded that TCM objective test provide an effective basis for the diag-nosis of bronchial asthma on aspects such as TCM syndrome, disease change observation and clinical evaluation.

This study was purposed to investigate the effect of 3'-azido-2', 3'-dideoxythymidine (AZT)on the proliferation and telomerase activity of human acute myeloid leukemia cell line KG-1a. The effect of proliferation was detected by MTT assay after the KG-1a cell were stimulated for 24, 48 and 72 h with different concentrations of AZT; telomerase activity was detected with TRAP-PCR-ELISA assay; RT-PCR was used to detect telomerase hTERT mRNA expression. The results showed that the proliferation of KG-1a cells was inhibited in a time and concentration dependent manner after exposure to AZT for 24, 48 and 72 h; the KG-1a cells decreased in S phase and increased in G(2)/M phase with the increasing of the concentration of AZT; telomerase activity and hTERT-mRNA expression in the experimental groups decreased after treated with AZT, which was positively correlated with concentration of AZT. It is concluded that AZT inhibits KG-1a cell proliferation and induces apoptosis, which maybe related with its decreasing the telomerase activity and hTERT mRNA expression.
Apoptosis ; drug effects ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Leukemia ; metabolism ; pathology ; Telomerase ; antagonists & inhibitors ; metabolism ; Zidovudine ; pharmacology

OBJECTIVETo evaluate tolerance and toxicity of high-dose epirubicin regimen CEF-100 as adjuvant therapy for breast cancer.

METHODSFrom March 2005 to October 2006, 98 patients with stage I - III a breast cancer were randomly assigned to receive postoperative chemotherapy with CEF-100 regimen (epirubicin 100 mg/m2, dl per 21 days for 6 cycles, n =48) or CEF-60 regimen (epirubicin 60 mg/m2, dl per 21 days for 6 cycles, n = 50). Blood routine test were done every cycle, liver and kindey function were examined and adverse effects were recorded after every cycle.

RESULTSNo difference of average leucocyte or neutrophil count (P >0.05) was observed in every cycle. Adverse effects of digestive tract and damage of liver function in CEF-100 group were more severe than that in CEF-60 group (P <0.05), but all adverse effects could be relieved by treatment. No severe non-hematological toxicity and cardiac toxicity in both groups were observed (P <0.05). There was no death caused by chemotherapy.

CONCLUSIONOur data shows that high dose epirubicin-containing CEF regimen is safe and tolerable for postoperative chemotherapy of breast cancer patient, and the adverse effects could be relieved by marrow support and liver-protection therapy. Further observation and longer follow-up is still needed in order to evaluate the efficacy of this high dose regimen.

Adult ; Alanine Transaminase ; blood ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Aspartate Aminotransferases ; blood ; Breast Neoplasms ; drug therapy ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; surgery ; Carcinoma, Lobular ; drug therapy ; surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide ; adverse effects ; therapeutic use ; Epirubicin ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Middle Aged ; Neutropenia ; chemically induced ; Vomiting ; chemically induced

Objective To evaluate a therapeutic strategy using aromatase inhibitors and TAM in postmenopausal Luminal B breast cancer patients. Methods The clinical data of 733 primary breast cancer cases receiving postoperative endocrine thempy from July 2002 to Mar 2005 in Tianjin Cancer Hospital were retrospectively analyzed.Diagnosis was confirmed by pathology in all the cases.All patients were post-menopausal and ER-positive.501 patients were given tamoxifen(TAM 2.5 mg qd,po),232 patients were given aromatase inhibitors(Letrozole 10 mg bid,po).The follow-up time ranged from 36 to 90 months.Median follow-up time was 46 months.Results The disease-free-survival(DFS)rate of Luminal B breast cancer patients in aromatase inhibitors(AIS)group was higherthan that in TAM group(90.6% vs.88.6%,P=0.038).In TAM group,subgroup analysis showed 3-year DFS of node-positive with HER2(+)is lower than that of node-positive with Her-2-negative(88.2% vs.90.4%,P=0.037);3-year DFS of ER+/PR+ group in HER2(+) patients was higher than that of ER+/PR-group(90.8% vs.89.5%.P=0.032).In AIs group,in spite of the axillary lymph node status,there was no significant difference of 3-year DFS between HER2(+)patients and HER2(-)ones(P>0.05).3-year DFS of ER+/PR+with HER2(+) patients was higher than that of ER+/PR-ones with HER2(+)(91.9% vs.90.5%,P=0.029).Hot flush,vaginal bleeding and thromboembolics in AIS group is less frequent,but muscle pain and bone fracture is more common than that in TAM group(P<0.05).Conclusion Compared to TAM, AIs is more effective and safer with postmenopausal Luminal B patients,and the effect is independent on node stams.

OBJECTIVETo summarize the experience of urethral reconstruction using circular fasciocutaneous flap for the treatment of complex anterior urethral strictures.

METHODThe circular fasciocutaneous flap was harvested from the distal penile shaft or foreskin. Then the circular configuration was converted into longitudinal strip of skin which was rotated to ventral side to repair the exposured urethral strictures using the ventral onlay method. The surveillance protocol after urethroplasty was urination observation, regularly uroflowmetry and urethrography examination.

RESULTSFrom Nov. 2006 to Oct. 2012, 15 cases were treated. The mean age was 45 years (20-76 years) and mean follow-up period was 18 months(3 months-3 years). Stricture was caused by chronic urethritis in 4 cases, long-term urethral catheterization in 3 cases, transurethral perfusion chem other aphy in 3 cases, transurethral prostatectomy in 3 cases and hypospadias after surgery in 2 patients. The mean stricture length was 7.0 cm (3.5-12.0 cm). The overall success rate was 80.0% (12/15). Recurrence stenosis was noted in 2 cases and diverticulum formation in 1 case.

CONCLUSIONSThe penile circular fasciocutaneous flap can be used for anterior urethral stricture in nearly any length. The flap has the characteristics of hairless, adequate mobile and length, well-vascularized pedicle and easy to harvest. The onlay reconstruction provides excellent cosmetic results, less trauma, higher success rate. Therefore it should be one of the preferred techniques for complex anterior urethral stricture repair.

Follow-Up Studies ; Foreskin ; Humans ; Hypospadias ; surgery ; Male ; Penis ; surgery ; Prostatectomy ; adverse effects ; Recurrence ; Surgical Flaps ; transplantation ; Urethra ; surgery ; Urethral Stricture ; etiology ; pathology ; surgery ; Urologic Surgical Procedures, Male ; Wound Healing