Exploration and optimization of processes for key intermediates of phosphorodiamidate morpholino oligonucleotides / 军事医学

Objective To explore and optimize the processes for synthesis of key intermediates of phosphorodiamidate morpholino oligonucleotides-7'-hydroxy-N-trityl morpholino nucleoside monomer in order to contribute to the research of phosphorodiamidate morpholino oligonucleotides antisense nucleotides.Methods With N-benzoylcytidine,guanosine and 5-methyluridine as starting materials,the ribose was modified to morpholino and the key chemical groups were protected to obtain 7'-hydroxy-N-trityl morpholino nucleoside monomer.Results Compounds N4-benzoyl-7'-hydroxy-N-trityl morpholinocytidine,N2-benzoyl-7'-hydroxy-N-trityl morpholinoguanosine and 7'-hydroxy-N-trityl morpholinothymidine were synthesized.The synthetic processes were optimized as well.The structures of all the intermediates and title compounds were characterized.Conclusion The synthetic processes of 7'-hydroxy-N-trityl morpholino nucleoside monomers have been optimized,which can be employed to prepare title compounds on a large scale.

Studies on hereditary epidemiology of cardia cancer in Shanxi province / 中华流行病学杂志

Objective Studies on cardia-cancer caused by hereditary factors. Methods Case-control method was adopted,with information including name,sex,date of birth,date of death of all the Ⅰ,Ⅱ,Ⅲ relatives of the patients,diagnosis and the treatment collected. The hereditary probability of cardia cancer and the separation degree were calculated by Falconer and Li-Mentel-Gart. Results (1) Prevalence rates of cardia-cancer on relative Ⅰ,relative Ⅱ,relative Ⅲ of cardia-cancer patients appeared to be 0.54%,0.04%,and 0.05% respectively. Prevalence rates of upper-digestive-tract-cancer of relative Ⅰ,relative Ⅱ,relative Ⅲ of cardia-cancer patients showed as: 2.50%,0.36% and 0.13% respectively. Data showed that relative Ⅰ> relative Ⅱ> relative Ⅲ and family cluster existed in both males and females. (2) Cardia-cancer hereditary probability of the relative Ⅰ cardia-cancer probands was 11.71%,with males as 14.01% and females as 14.72%. The upper-digestive-tract-cancer hereditary probability of the relative Ⅰ cardia-cancer probands was 13.87%,with males as 11.49% and females as 23.08%,both below 25%,indicating this was a low hereditary cancer. (3) The upper-digestive-tract-cancer separation of the blood compatriots of cardia-cancer patients was 0.0452,with males as 0.0441 and females as 0.0507,both below 0.25,indicating the nature of a multi-gene but not single-gene hereditary way. Conclusion Hereditary factor is recognized as one of the high risk cardia cancer,but not the most risky factor causing the high morbidity of cardia cancer in Shanxi province.

A comparative study on the risks of esophagus-cancer patients among factors as blood relatives,paternal line,matriarchal and different sex / 中华流行病学杂志

Objective In order to provide new clues on the cause of esophagus-cancer through seeking for information among the relatives of esophagus-cancer-patients at high-risk,contrast analysis was carried out to compare the ORs between esophagus-cancer cases and the relatives of the patients.Methods Case-control study was adopted on 720 cases and 720 controls who were kin relatives of the patients.Results (1) Risk of the relatives to the esophagus-cancer-patient group ( 1.34%-2.24% ) was obviously higher than the control group (0.78%-1.21%) (P＜0.01).In 1st grade relatives,the risk of parent' s to the esophagus-cancer patients (6.11% ) was obviously higher than the control group (2.97%) (P＜0.01 ).(2) According to the cascade analysis to the cases of both paternal and matriarchal,lines,results showed that the risks of both the paternal line (0.87%-1.01%) and the matriarchal line (0.50%-0.79%) in the group of esophagus-cancer cases were all obviously higher than the lines in the control groups (0.53%-0.65%) and (0.38%-0.47%).Data also showed that the risk among the male relatives of paternal line (eg:grandfathers',father' s,uncles' etc.) in the group of cases was 2.68% while the matriarchal (eg:grandmother's,mother' s,aunts' etc.) was 1.91%.Both figures were obviously higher than that in the control group (1.50% and 0.92%,P＜0.01 ).Conclusion The risk factor of esophagus cancer of the next generation seemed higher if the father and his brothers or mother and her sisters having had esophagus-cancers.

Testosterone induces different-featured prostate hyperplasia in castrated and uncastrated mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the different features of hyperplasia in castrated and uncastrated mice after testosterone (T) treatment.</p><p><b>METHODS</b>Forty-eight BALB/c mice were randomly divided into 6 groups of 8 in each: castrated (A), uncastrated (B) , castrated + low T (C), uncastrated + low T (D), castrated + high T (E), uncastrated + high T (F). Groups C and D were treated with testosterone solution at the dose of 12.5 mg/(kg d) and Groups E and F at 125 mg/(kg d) for 20 consecutive days, while Groups A and B received saline only. All the mice were sacrificed on the 21st day, their ventral and dorsal prostate glands weighed and their pathological features studied.</p><p><b>RESULTS</b>Atrophic prostates were observed in Group A, but normal in Group B; prostatic hyperplasia was found in both Group C and D, but more obvious in the latter (P <0.05); and a slightly higher degree of hyperplasia was noted in Groups E and F than in C and D. There was an increase in serum T and vascular endothelial growth factor (VEGF) concentration and a decrease in serum estrogen (E2) concentration in the testosterone treated groups.</p><p><b>CONCLUSION</b>Both castrated and uncastrated mice develop prostate hyperplasia after short-term testosterone treatment, although in different degrees and with different features, which may help further the studies on the association of castration and androgen with prostate diseases.</p>

Expression of GLUT-1, p63 and DNA-Pkcs in serous ovarian tumors and their significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of GLUT1, p63 and DNA-Pkcs in serous ovarian tumors and their significance.</p><p><b>METHODS</b>GTUL1, p63 and DNA-Pkcs expression at protein level was detected by immunohistochemistry in patients with serous ovarian tumors. Chi-square analysis was used to assess if their expression is associated with clinicopathologic characteristics of the tumors.</p><p><b>RESULTS</b>Cells in the normal ovarian tissues were not stained with GTUL1 and p63 antiserum, but DNA-Pkcs was positively stained. The intensity of GTUT1 and p63 expression was stronger in malignant ovarian serous tumors compared with other subtypes (P < 0.01). There were significant differences of DNA-PKcs among normal ovaries (100.0%), benign (95.0%), borderline (90.0%) and malignant (60.0%) serious ovarian neoplasms (P < 0.01). The level of GLUT-1 expression was correlated with FIGO staging, intraperitoneal implantation, ascites and lymph node metastasis (P < 0.05). p63 expression was associated with clinicopathologic characteristics except ascites (P < 0.05). DNA-PKcs was only correlated with FIGO staging and lymph node metastasis (P < 0.05).</p><p><b>CONCLUSION</b>The results suggest that the abnormal expression of GTUT1, p63 and DNA-Pkcs may perhaps participate in serous ovarian tumor occurrence and development and may be considered as a marker reflecting tumor malignant behavior.</p>

Expression of caspase-3 survivin CyclinD1 and p27 in gastric carcinoma and their significance / 肿瘤研究与临床

Objective To study the expression of caspase-3,survivin,CyclinD1 and P27 in gastric carcinoma(CA2)and the relationship between the biomarkers and clinical pathological parameters. Methods Immunohistochemical Ready-to-use two-steps method was performed to research the expression of the four proteins in 72 cases of GC,and 54 cases of normal gastric mucosa.Results The expression level of caspase- 3 and p27 protein in GC was significantly lower than that in normal gastric mucosa(P

Study on microsatemte instability of p14,p15,p16 gene in gastric carcinoma / 肿瘤研究与临床

Objective To detect the microsatellite instability (MSI) of D9S166,D9S171,D9S941, D9S942 and IFNA located at chromosome 9p21 in gastric carcinoma with high-grade intraepithelial neoplasia and normal tissue,and investigate the correlation of p14,p15,p16 gene and the gastric carcinogenesis. Methods 55 cases of gastric carcinoma with high-grade intraepithelial neoplasia and normal tissue were se- lected to detect MSI by microdissection,polymerase chain reaction,denaturing polyaerylamide gel elec- trophoresis and silver nitrate staining technology of five microsatellite markers on 9p21.Results In the infor- mative cases,total ratio of MSI in gastric carcinoma was 27 % (64/233) and it was 18% (42/233) in high- grade intraepithelial neoplasia.The ratio of MSI was significantly higher in gastric carcinoma than that in high-grade intraepithelial neoplasia (P

Expression of high-risk HPV and p53,p21~(WAF1),MDM2 in cervical squamous cell carcinoma / 肿瘤研究与临床

Objective To determine the expression of HPV16/18,31/33 DNA and p53,p21~(WAF1) and MDM2 proteins in invasive squamous cell carcinoma of cervix (ISCC)and to indicate the significance of them in the occurrence and development of ISCC.Methods Using tissue microarray,in situ hybridization (ISH) and immunohistochemical method,we detected the expression of HPV16/18,31/33 and investigate the expres- sion of p53,p21~(WAF1),MDM2 and proteins in ISCC,CIN and NCE.Results was analysed by SPSS vision 12.5. Results The positive expression rate of HPV16/18,p53,p21~(WAF1),MDM2 in ISCC was markedly higher than in CIN and NCE.We found the difference between HPV31/33 and lymph node transfer.Significant relation- ship was observed between p53 protein expression and histological grade and lymph node metastasis of the cancer.There was positive correlation between the expression of p21~(WAF1) protein and the depth of invasion(P

Loss of heterozygosity in esophageal squamous cell carcinoma and its precursor lesion / 中华病理学杂志

<p><b>OBJECTIVE</b>To detect the loss of heterozygosity (LOH) in esophageal squamous cell carcinoma and adjacent high-grade squamous dysplasia, and to evaluate possible tumor suppressor genes in the development and progression of invasive malignancy.</p><p><b>METHODS</b>LOH was detected in normal esophageal mucosa, high grade squamous dysplasia and esophageal squamous cell carcinoma using microdissection and polymerase chain reaction technology. The changes of LOH at seven microsatellite markers and the relationship between LOH rate and clinicopathologic parameters were analyzed.</p><p><b>RESULTS</b>In high grade squamous dysplasia, LOH was detected at D13S802 (40%), D13S267 (32%), D13S221 (31%), D9S942 (30%), D17S520 (24%) and D9S171 (33%). However, D17S1798 LOH was not detected. In invasive squamous cell carcinoma, LOH was detected as follows: D13S267 (71%), D13S802 (58%), D17S520 (55%), D13S221 (45%), D9S942 (43%), D9S171 (33%) and D17S1798 (11%). The frequency of LOH in the seven microsatellite markers, the pathologic grade, clinical stage and occurrence of lymph node metastasis did not show any statistically significant correlation (P > 0.05).</p><p><b>CONCLUSIONS</b>The progression from normal squamous epithelium to high grade squamous dysplasia and subsequently to invasive squamous cell carcinoma of the esophagus was associated with accumulation of genetic errors. Possible tumor suppressor genes related to the development of esophageal squamous cell carcinoma may exist near D13S802 (13q12.12). Possible tumor suppressor genes near D13S267 (13q13.1), D17S1798 (17p13.3) and D17S520 (17p13.1) may be related to the progression of esophageal squamous cell carcinoma.</p>