The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

OBJECTIVETo explore the methods of isolation, cultivation, purification, identification of the fetal mice testis Leydig cell and to observe its biological characteristics in vitro.

METHODSLeydig cells were isolated by 0.03% collagenase (type I) from fetal mice testis and cultured in DMEM/F12 medium. The identity and purity of Leydig cell were assessed by 3beta-hydroxysteroid dehydrogenase delta4-delta5 isomerase (3beta-HSD). Cell viability was measured by trypan blue. Testosterone level in the medium of cultured Leydig cells was measured in various culture phases and cell density by radioimmunoassay.

RESULTSThe purity of Leydig cell was (45.10 +/- 1.66)% before culture, and (81.17 +/- 2. 32)% 72 h after culture. The level of testosterone secreted by Leydig cells could be detected in the medium and its level was associated with the density and time of cultured Leydig cells. The secretion capacity of testosterone by single Leydig cell decreased gradually during the culturing period.

CONCLUSIONThe fetal Leydig cells isolated from fetal mice testis have high purity. It can be cultured and kept the secretion ability of testosterone for a few days in vitro. This system can provide a valuable model for further study on the cellular function of the Leydig cells of fetal mice.

Animals ; Cell Separation ; Cells, Cultured ; Leydig Cells ; cytology ; physiology ; Male ; Mice ; Mice, Inbred Strains ; Testis ; embryology ; Testosterone ; secretion

Objective To analyze the relevant data,including medical history,treatment and nursing of one cysticercosis patient with multiple foci in Baise City,so as to provide the evidence for improving the treatment and nursing of cysticercosis in the future.Methods The data of diet history,diagnosis,treatment and nursing of the patient were collected and analyzed.Re-sults The patient was a permanent resident in a cysticercosis high endemic area and had a definite history of eating measly pork. The combination of clinical manifestations and auxiliary examinations of the patient confirmed that he was suffered from cysticercosis with multiple foci.After the patient was firstly administered the antiparasitic treatment of cysticercosis(praziquan-tel),he had status epilepticus.However,with the close cooperation between physicians and nurses,his illness obviously im-proved and 35 days later,he discharged.Conclusion The physicians and nurses should pay much attention to the changes of illness of the patients with cysticercosis,especially the cysticercosis patients with multiple foci in the antiparasitic treatment of cysticercosis,so as to avoid cerebral herniation due to the increased intracranial pressure.

Objective To study the requirements for defibrillation protection testing and marking of the multi-parameter monitor to facilitate the manufacturer to understand related standards and design products rationally.Methods The background and principle were described for defibrillation protection testing of the monitor.The requirements of related standards were analyzed for defibrillation protection testing and marking,and the defibrillation protection flow was explored during the clinical application of the monitor.Results The multi-parameter monitor might be damaged in case of the monitor's deficiencies in the the defibrillation protection,even patient's failure in the defibrillation protection or death might occur,and the electrical shock could be caused also to medical staffs.Conclusion The defibrillation protection is of great significance for the multi-parameter monitor,and considerations have to be posed on standards requirements and the monitor's clinical application so as to decrease its use risks.

Objective To analyse the preliminary clinical results of intensity modulated radiation therapy (IMRT) for 122 untreated nasopharyngeal carcinoma (NPC)pafients.Methods 122 NPC pa- tients received IMRT alone from Feb.2001 to Jun.2004,with 31 females and 91 males,and a median age of 45 years(range 25-66).According to the Fuzhou Stage Classification,there were StageⅠ11 patients, StageⅡ34,StageⅢ62,and StageⅣa 15.IMRT was carried out using an inverse planning system (COR- VUS 5.0,Peacock plan) developed by the NOMOS Corp.The treatment was given with the Multi-leaf Inten- sity Modulating Collimator (MIMIC) using a slice-by-slice arc rotation approach.The prescription dose was 68 Gy/30f to the nasopharynx gross tumor volume (GTV_(nx)),60-66 Gy/30f to positive neck lymph nodes (GTV_(nd)),60 Gy/30f to the first clinical target volume (CTV_1) and 54 Gy/30f to the second clinical target volume (CTV_2).Kaplan-Meier method was used to calculate the overall survival rate (OS),distant metas- tasis-free survival rates (DMFS),and local-regional control rates from the last date of therapy.Log-rank test was used to detect the difference between groups.Results The median follow-up time was 20 months ( range 6 to46 months).The 1-,2-,and 3-year OS was 95.2%,91.4%,85.1%,DMFS was 91.9%, 88.6%,85.6%,and the local-regional control rates was 96.5%,93.2%,93.2%,respectively.Statistics of the local control rate was insignificant either for advanced T(T3+T4) stage or early T(T1+T2) stage diseases(P=0.148).The 2-year regional control rate was insignificant either for patients with N(+) or N (-),but the 2-year DMFS was significant both for patients with N(+) and N(-)lesions(P=0.004).For 17 patients who failed,there were two with residual disease and one with recurrence at the primary site (17.6%),three patients in the neck (17.6%),twelve patients (70.6%) in distant metastases.Conclu- sions Intensity modulated radiation therapy does provide excellent local-regional control for untreated NPC, especially in patients with advanced T stage or N(+) lesion.Distant metastasis is the main cause of failure. N (+) is significantly correlated with distant metastasis.

Objective To investigate the effect of leptin on the tolerance of cultured rat brain astrocytes to ischemia and hypoxia.Methods The brain astrocytes isolated from neonatal SD rats,after purification and identification,were incubated in serum-and glucose-flee medium in the presence of 5%CO2+95%N2 for 90 min to induce isehemic and hypoxic injury. RT-PCR was performed to detect the expressions of the leptin receptors Ob-Ra and Ob-Rb in the cells, and colorimetry was used to measure the content of malonaldehyde(MDA) and lactate dehydrogenase(LDH) activity in the cell supematant.The expression level ofglial fibrillary acidicprotein(GFAP)in the cells was detected with fluorescence immunocytochemistry.Results Ischemic and hypoxic exposure of the cells induced obvious cell necrosis.Compared with the cells without the exposure,significantly decreased Ob-Rb expression(0.52±0.01 vs 1.32±0.01,P<0.05)and increased MDA,LDH and GFAP levels(709.68±47.16 vs 516.13±29.08,3.94±0.36 vs 1.81±0.21,and 0.122±0.016 vs 0.057±0.006,respectively,P<0.05) occurred after the exposure,whereas the expression level of Ob-Ra underwent no significant changes(3.87±0.13 vs 3.96±0.24,P>0.05). Compared with the exposed cells,the leptin-treated cells showed a significant reduction in MDA levels(3.94±0.36 vs 3.19±0.25,P<0.05) with significantly increased GFAP expression(0.057±0.006 vs 0.109±0.008, P<0.05)after the exposure, and the cells maintained basically intact cell morphology.Conclusion With neuroprotective effects against ischemic neuronal injuries,leptin canimprove the tolerance of rat brain astrocytes to ischemia and hypoxia.

OBJECTIVETo explore the effects of Di (2-ethylhexyl) phthalate (DEHP) on the testis and testicular gubernaculum of fetal KM mice in vivo and to investigate the mechanism of DEHP-induced cryptorchidism.

METHODSThirty healthy pregnant KM mice were randomly and equally divided into a blank control group, a corn oil control group and a DEHP group. The pregnant mice in the latter group were exposed to DEHP by gavage at the dose of 500 mg/kg body weight per day from gestation day 12 (GD12) through gestation day 19 (GD19). The effects of DEHP were observed on the number of fetuses per pregnancy, the ratio of male to female pups, the weight of the testis, the morphology and location of the testis and gubernaculum, the relative testis-bladder neck distance (TBD) and cranial suspensory ligament (CSL) residual. The expressions of the androgen receptor (AR), estrogen receptor (ER) and actin and proliferating cell nuclear antigen (PCNA) in the gubernaculum were detected by immunohistochemistry.

RESULTSDEHP reduced the testis weight and TBD, induced different degrees of testis maldescent, but produced no obvious effect on the body weight, the number of fetuses per pregnancy, the sex ratio and the testis gubernacular morphology. Under the light microscope, hypotrophy was seen in all the testis seminiferous tubules, spermatogenic cells and Sertoli cells, marked Leydig cell hyperplasia was noted, and the positive expression of AR in the gubernaculum was decreased in the DEHP group (P < 0.01).

CONCLUSIONDEHP could cause dysfunction of the testis gubernaculum via its anti-androgen effect, induce cryptorchidism, and cause dysplasia and dysfunction of Sertoli cells, Leydig cells and spermatogenic cells in fetal mice.

Animals ; Diethylhexyl Phthalate ; pharmacology ; Female ; Fetus ; drug effects ; Leydig Cells ; drug effects ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; Sertoli Cells ; drug effects ; Testis ; cytology ; drug effects ; pathology

OBJECTIVETo evaluate the feasibility, toxicity and tumor control of intensity modulated radiation therapy (IMRT) for recurrent nasopharyngeal carcinoma.

METHODSFourty-nine patients (Karnofsky performance status (KPS) >or= 80) with local-regional recurrence in the nasopharynx were treated with full course IMRT. Three patients with cervical lymph node metastasis (N1 2 and N3 1) were further supplemented with 5 to 6 courses of chemotherapy (Cisplatin + 5-Fu) after IMRT.

RESULTSThe results of treatment plan showed that the mean dose of covering gross tumor volume (GTV) (D(95)) in the nasopharynx was 68.09 Gy and the mean volume of GTV (V(95)) receiving the 95% dose was 98.46%. The mean dose of GTV, clinical target volume CTV1 and CTV2 in the targets were 71.40 Gy, 63.63 Gy and 59.81 Gy. The median follow-up time was 9 months (range 3 to 16 months). The local-regional progression-free survival was 100% with local-regional residual disease in 3 (6.1%) cases but was complicated with nasopharyngeal mucosa necrosis in 14 (28.6%) cases after IMRT.

CONCLUSIONIntensity modulated radiation therapy, as a re-treatment option for recurrent nasopharyngeal carcinoma, is able to improve the tumor target coverage and spare the adjacent critical structures. As high dose IMRT can result in radio-necrosis of nasopharyngeal mucosa, the prescription dose of GTV should be suitably decreased to 60 - 65 Gy.

Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Neoplasm Recurrence, Local ; radiotherapy ; Neoplasm Staging ; Radiation Injuries ; pathology ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; methods

OBJECTIVETo explore the effects of di(2-ethylhexyl)phthalate (DEHP) on neonatal mice's testes and Leydig cells in vivo.

METHODSPregnant mice were exposed to DEHP at the dose of 100 mg/kg, 200 mg/kg or 500 mg/kg (body weight) per day by gavage from gestation day 12 (GD 12) through postnatal day 3 (PND 3), respectively. The testis and body weights, testicular histopathology and the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) of the neonatal mice were investigated.

RESULTSThe body and testis weights of the male mice's offspring were significantly reduced following DEHP exposure. Leydig cell morphology was affected significantly by DEHP as compared with the controls. Leydig cells obviously increased in the neonatal mice's testes on PND 15 and PND 30 when exposed to DEHP (500 mg/[kg x d]). Activities and positive area of the steroidogenic enzymes 3beta-HSD immunoexpression decreased markedly when exposed to DEHP (100 mg/[kg x d] or 200 mg/[kg x d]). Image analysis showed a decrease in the activities of 3beta-HSD in the animals exposed to DEHP (500 mg/[kg x d]), but an increase in the positive area of 3beta-HSD immunoexpression as compared with the control animals on PND 15 (P < 0.01).

CONCLUSIONDEHP affects the Leydig cell morphology, the activity of 3beta-HSD, the testis and body weights and the testicular histopathology of neonatal mice, and it may function as an antiandrogenic agent.

3-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Animals, Newborn ; Diethylhexyl Phthalate ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Leydig Cells ; cytology ; drug effects ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; Prenatal Exposure Delayed Effects ; Testis ; drug effects

OBJECTIVETo evaluate the application of ileocecum interposition (ii) graft as pylorus replacement in alimentary reconstruction.

METHODSTwenty- one minipigs were randomly divided into three groups: sham operation group (control group), B - i group and ii group. The levels of blood glucose were measured by quick blood glucose testing of paper at 0, 30, 60, 90, and 120 minutes of oral glucose after 60 and 120 post- operative days to compare gastric emptying of liquid feeds.

RESULTSTwo months after operation,the peak of blood glucose was (7.8+/- 1.0)mmol/ L, (7.1+/- 0.8)mmol/ L, (4.1+/- 0.4)mmol/ L in B - i, ii group and control group respectively, there were significant differences between the two operation groups and control group (P< 0.01). Four months after operation, the peak of blood glucose was (6.9+/- 1.0) mmol/ L, (5.2+/- 0.8)mmol/ L, (4.2+/- 0.5)mmol/ L, respectively, there was no significant difference between ii group and control group (P > 0.05),but there were significant differences between both of the above two groups and B - i group (P< 0.01).

CONCLUSIONThe ileocecum interposition graft can offer specific advantages over current reconstruction procedures.

Animals ; Blood Glucose ; metabolism ; Female ; Gastric Emptying ; Glucose Tolerance Test ; Ileocecal Valve ; transplantation ; Male ; Pylorus ; surgery ; Swine ; Swine, Miniature