Objective To study the radiosensitization of histone deaeetylases inhibitor(HDACI) panobinistat in prostate cancer cells in vitro,as well as the possible mechanisms.Methods IC20 of two prostate cancer cell lines(LNCaP and PC-3)was determined using MTI assay.Cells received a single dose irradiation of 0,2,4,6,or 8 Gy using 6 MV X-ray for radiosensitivity experiment,but only 2 Gy for western blot and flow cytometry.Radiosensitization of panobinostat was investigated with clonogenic assay,and sensitizing enhancement ratio(SER)was calculated with single-hit multi-target model.Western blot was used to compare γH2AX expression.Flowcytomctry was used to detect the cell cycle distribution.Results IC20 of LNCaP and PC-3 was 2.5 and 10.0 μmol/L,respectively.SER of panobinostat at IC20 was 1.37(D0 ratio)and 1.11(Dq ratio)for LNCaP cells,and 1.78(D0 ratio)and 1.17(Dq ratio)for PC-3 cells.Expression of γH2AX gradually decreased in the 2 Gy irradiation-alone cells standing for the DSB repair,while γH2AX expression was persistent in the combination group.Irradiation triggered a G2/M arrest 6-12 hours after irradiation in LNCaP and PC-3 cells.G2/M arrest was observed when cells were treated with panobinostat for 24 hours,however,no significant change concerning cell cycle distribution was showed when cells received further irradiation.Conclusions Panobinostat Call radiosensitize prostate cancer cells,which may be related with increased DNA DSB,inhibition of DSB repair and attenuation of cell cycle modulation after irradiation.

Objective To re-evaluate the prognostic value of the 6th edition of UICC/AJCC staging system in patients with nasopharyngeal carcinoma (NPC) treated with intensity-medulated radiation therapy (IMRT). Methods From February 2001 to March 2007, Clinical data of 570 NPC patients initially treated with IMRT in Cancer Center of Sun yat-sen University were reviewed and the long-term survival was analyzed according to T, N and overall stages. Results The median follow-up was 42 months. 184 patients were followed up to 5 years. The 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) of the whole group were 93. 0%, 85.4% and 83. 3% ,respectively. No statistically significant difference of LRFS was detected between the either two of stage T_1, T_(2a) and T_(2b)(100%, 100% and 94. 5% ;T_1 vs. T_(2b), χ~2 = 1.92, P =0. 166 ;T_(2a) vs. T_(2b), χ~2= 0. 35, P =0. 555), stage T_(2b) and T_3 (94. 5% and 91.3% ;χ~2 = 2. 62, P = 0. 106), or stage T_3 and T_4 (91.3% and 89. 5% ; χ~2 = 1.55, P =0. 214). The 5-year DMFS of stage N_2 was similar with stage N_1 or stage N_3(80. 2%, 86. 2% and 61. 4% ; N_2 vs. N_1, χ~2=2.22, P=0.136;N_2 vs. N_3, χ~2= 1.92, P=0.165). No statistically significant difference of 5-year OS was observed among stage Ⅰ , Ⅱ_a and Ⅱ_b(91.7%, 100% and 95. 3% ; Ⅰ vs. Ⅱ_b χ~2 =0.32, P=0.574;Ⅱ_a vs. Ⅱ_b,χ~2-0.25, P=0.617), or between Ⅳ. And Ⅳ_b(67.9% and 75. 0% ;χ~2 = 0.25, P = 0. 616). Conclusions The 6th edition of UICC/AJCC staging system shows poor predictive value for the long-term survival of NPC patients treated with IMRT.

Adult ; Calcinosis ; diagnostic imaging ; pathology ; surgery ; Cysts ; diagnostic imaging ; pathology ; surgery ; Diagnosis, Differential ; Female ; Humans ; Lymphatic Vessel Tumors ; pathology ; Mucocele ; pathology ; Parasitic Diseases ; pathology ; Spleen ; diagnostic imaging ; Splenectomy ; Splenic Diseases ; diagnostic imaging ; pathology ; surgery ; Tomography, X-Ray Computed

Objective To observe the influence of patient′s age, and the number of transferred-good-quality-embryos on multiple gestation rates in in vitro fertilization and embryo transfer(IVF-ET) cycles. Methods In this retrospective study, a total of 4395 patients who transferred fresh embryo between Jan 2004 and Nov 2006 was analyzed. According to the age, the patients were divided into 2 groups: aged < 35 (3442 cycles) or aged ≥135(953 cycles). We regularly transferred 2 -3 embryos. If the patients had only one embryo, one was transferred. And those patients who had only 2 embryos, even if they were more than 35 years old or it would be the second time for them to transfer, were transferred 2 embryos. The influence of female age and the number of good quality embryos transferred on the multiple gestation rates in IVF-ET cycle was analyzed. Results (1)The multiple gestation rate of the groups of 1 good quality embryo,2 good quality embryos, or 3 good quality embryos transferred were 21.08% (35/166), 31.41% (413/1315), and 42. 37% (75/177), respectively in women aged < 35, with a significant difference between them. The pregnancy rates of these groups were 29. 64% (166/560) ,51.63% (1315/2547) ,and 52. 84% (177/335), respectively; there were no significant differences between 2 good quality embryos transferred group and 3 good quality embryos transferred group. (2) The multiple gestation rates of the groups of 1 good quality embryo,2 good quality embryos, or 3 good quality embryos transferred were 19. 51% (8/41) ,20. 65% (19/ 92) ,and 40.66% (74/182), respectively, in women aged ≥ 35; there were no significant differences between 1 good quality embryo transferred group and 2 good quality embryos transferred group. The pregnancy rates of these groups were 19. 07% (41/215), 33.70% (92/273), and 39. 14% (182/465), respectively; there were no significant differences between 2 good quality embryos transferred group and 3 good quality embryos transferred group. (3) The pregnancy rate of the patients aged <35 [48. 17% ( 1658/ 3442) ]was significantly higher than in women aged ≥35[33.05% (315/953) ]. Conclusion The transfer of 2 good quality embryos results in similar pregnancy rates and significantly reduced multiple gestation rates when compared to the transfer of 3 good quality embryos in women regardless of their ages.

Objective To report the clinical outcome and prognostic factors for locally recurrent nasopharyngeal carcinoma(NPC)treated with intensity modulated radiotherapy(IMRT).Methods From January 2001 to August 2004,the data of 132 such NPC patients were analyzed retrospectively;104 male and 28 female with a median of 44.5 years(range 21-73 years).Ninety-eight patients(74.2%)were confirmed by biopsy as having NPC:9 with WHO TypeⅡand 89 WHO TypeⅢ.The other 34 patients were only diagnosed by MRI scan because of the extension/invasion was in the base of skull and/or cavernous sinus.Median interval time were 24 months(range 6-184 months).According to the 1992 Chinese Fuzhou Staging System:stageⅠ3.8 %,Ⅱ10.6 %,Ⅲ22.0% andⅣa 63.6%;T1 5.3%,T2 10.6%,T3 22.7% and T4 55.3%.Twenty-two patients had recurrence in the neck lymph nodes.IMRT was given with the sequential tomotherapy system(NOMOS Peacock systems)of 6 MV X-rays.Prescription dose was 60-70 Gy in GTV,with the fractional dose of 1.94-2.8 Gy.Sixty patients were also supplemented with two to six courses of cisplatin-based chemotherapy.Results The median volume of GTV was 39.5 cm~3(range 0.8-158.9 cm~3).The D95,V95,mean dose and fractionation dose of GTV was 66.9 Gy,98.3%,69.8 Gy and 2.32 Gy,respectively.The median follow-up time was 12 months(range,2-47 months).The 1-,2-and 3-year local progression-free rate was 96.4%,88.4% and 85.3%,respectively.The overall 1-,2-and 3-year survival rate was 6.5.9%,49.6% and 41.6%,respectively.Eleven patients developed distant metastases.Forty-seven patients were observed to devdop mucosa necrosis and/or massive hemorrhage in the nasopharynx.On univariate and multivariate analysis,fractional dose and vohane of GTV were significant prognostic factors for overall survival(P=0.016,0.009).Conclusions The local control and survival rate can be improved for patients with locally recurrent nasopharygeal carcinoma after treatment of intensity modulated radiotherapy.The fractional dose and volume of GTV are independent prognostic factors for the overall survival. The main death reasons are mucosa necrosis and/or massive hemorrhage in the nasopharynx.

The high performance liquid chromatography-fluorescence micelle assay (HPLC-FMA) method for the content determination of polysorbate 80 in monoclonal antibody drugs was validated to study its applicability and transferability between various laboratories, and the feasibility to be included in the Chinese Pharmacopoeia. Both J.T. Baker and Nanjing Well-sourced polysorbate 80 was used in the collaborative validation of polysorbate 80 content analysis in seven different laboratories. The results show that when the protein concentration was no more than 20 mg·mL^-1 and the concentration of polysorbate 80 ranged from 0.05 to 0.5 mg·mL^-1, the method had good specificity. The recovery rates of the spiked samples ranged from 92.20% to 117.70% for J.T.Baker and from 93.90% to 117.20% for Nanjing Well. The intra-laboratory precision (%RSD) was less than 4.30% for J.T. Baker, and less than 2.60% for Nanjing Well, while the overall precision was less than 5.45% for J.T. Baker, and less than 6.70% for Nanjing Well. The linear correlation coefficient was more than 0.98 for J.T. Baker and more than 0.99 for Nanjing Well. The results of the collaborative validation prove that the HPLC-FMA method has good accuracy, precision, linearity, and specificity, and could be used for release control analysis of polysorbate 80 content in monoclonal antibodies across different laboratories.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.
Absorption, Physicochemical ; Adhesiveness ; Administration, Ophthalmic ; Animals ; Drug Carriers ; Eye ; metabolism ; Fluoresceins ; chemistry ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Wheat Germ Agglutinins ; administration & dosage ; chemistry ; pharmacokinetics

Objective To compare the Chinese'92 and 2008 staging systems of nasopharyngeal carcinoma (NPC) based on the long term survival of the patients. Methods Clinical data of 498 NPC patients treated with definitive IMRT were retrospectively analyzed. The distributions of patients in the two staging systems were compared. The long term outcomes according to T, N and overall stages in each system were evaluated. Kappa value and Pearson coefficient were used to evaluate the agreement and correlation of the two systems. Results The distributions of both T and N stage between'92 and 2008 stage systems were different. In both staging systems, the local recurrence-free survival (LRFS) curves of T_1, T_2 andT_3 were close up (even overlaped), though they were apart from T_4. The distant metastasis-free survival (DMFS) curves overlaped of N_1 and N_2 in the'92 staging system, while separated of N_1, N_2 and N_3 in the 2008 staging system. Significant difference of DMFS was not found between N, and N_2 in'92 staging system, while did exist among N_0, N_1, N_2 and N_3 stages in 2008 staging system. In the both staging systems, the disease-specific survival (DSS) of stage Ⅰ did not significantly differ from that of stage Ⅱ or Ⅲ. The statistical analysis showed the conformality of DSS curves in the two system was 89% (Kappa =0. 833 ,P <0.01), with agood relative rate (r=0. 919,P<0. 01). Conclusions The difference between'92 and 2008 staging system is mainly in N stage. The 2008 N stage seems more reasonable compared with'92 N stage, which is able to better forecast the DMFS. There are some agreements and correlations between the two staging systems.

Objective To evaluate the outcomes and toxicities of early stage nasopharyngeal carcinoma(NPC)patients treated with intensity-modulated radiotherapy(IMRT)alone. Methods From February 2001 to January 2008, 198 early stage NPC patients according to AJCC/UICC 2002 staging system were treated by radical radiotherapy with IMRT technique in our institute, the clinical data were analyzed retrospectively. Results The 5-year disease-specific survival, local recurrence-free survival(LRFS)and distant metastasis-free survival(DMFS)were 97.3%, 97.7% and 97. 8% respectively. The 5-year LRFS for T1, T2 patients were 100%, 96. 7%(x2 = 2. 24 ,P = 0. 135)respectively. The 5-year DMFS for T1 N0,T2N0, T1N1, and T2N1 patients were 100%, 98. 8%, 100% and 93. 8%(x2= 2. 35, P= 0. 125)respectively. Grade 1 and 2 mucositis and pharyngitis were most common acute toxicities. Radiation encephalopathy and cranial nerve injury were not observed in all patients. Conclusions IMRT alone for early stage NPC patients can produce satisfactory results and acceptable treatment-relative toxicities. Patients with T2b and T2bN1 had a relatively higher incidence of local recurrence and distant metastasis, which suggested that combination of IMRT and chemotherapy may improve clinical results in those patients.

Objective To investigate the long-term outcomes of patients with nasopharyngeal carcinoma (NPC) in different stages treated by intensity-modulated radiotherapy (IMRT) and explore their treatment strategies.Methods A retrospective analysis was performed on the clinical data of 868 NPC patients without distant metastasis who received radical IMRT from May 2001 to October 2008.These patients were divided into early N0 (T1-2N0) group (n =137),early N1 (T1-2N1) group (n =129),locally advanced (T3-4N0-1) group (n =322),regionally advanced (T1-2 N2-3) group (n=107),and locoregionally advanced (T3-4 N2-3) group (n =173).There groups were compared in terms of treatment outcome and treatment strategy.Results The follow-up rate was 91.4％,and 314 patients completed 5-years follow-up.The 5-year overall survival rate,local recurrence-free rate,and distant metastasis-free rate (DMFR) were 83.5％,91.8％,and 84.6％,respectively.The early N0 group had the best treatment outcome,with a 5-year disease-specific survival (DSS) rate up to 99.1％.Each group had a similar outcome after receiving either IMRT alone or IMRT combined with chemotherapy.The locally advanced group and regionally advanced group had similar failure patterns and treatment outcomes.The locoregionally advanced group had the worst treatment outcome,with a 5-year DMFR of 67.2％ and a DSS of 68.0％.The regionally advanced group and locoregionally advanced group had a similar treatment outcome after receiving IMRT alone,induction chemotherapy plus IMRT,or concurrent chemotherapy and IMRT.Conclusions Patients with NPC in different stages have different survival outcomes.It is recommended that different treatment strategies should be adopted according to the T and N stages of NPC.IMRT alone can produce satisfactory results in patients with T1-2N0 NPC,but a more effective medication should be added to IMRT in patients with advanced NPC,particularly those with T3-4N2-3 NPC who have a relatively low DMFR.