Journal of cellular biochemistry. Supplement最新文献

{"title":"Polyamine measurements in the uterine cervix.","authors":"M F Mitchell,&nbsp;G Tortolero-Luna,&nbsp;J J Lee,&nbsp;W K Hittelman,&nbsp;R Lotan,&nbsp;J T Wharton,&nbsp;W K Hong,&nbsp;K Nishioka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cervical cancer remains a significant health problem. New strategies based on the molecular aspects of cervical carcinogenesis are needed. Chemoprevention represents a novel strategy for cervical cancer prevention. Our group plans phase I and II trials using alpha-difluoromethylornithine, a suicide inhibitor of ornithine decarboxylase and potent antiproliferative chemopreventive agent. We conducted a study to identify which polyamines in tissue could best serve as surrogate endpoint biomarkers for future trials. Thirty patients with biopsy-proven cervical intraepithelial neoplasia grade 3 underwent colposcopically directed biopsies of normal and abnormal areas of the uterine cervix for analysis of polyamine synthesis biomarkers. Statistically significant differences were found in the ornithine decarboxylase value and the spermidine:spermine ratio between normal and abnormal areas of the cervix. In general, the ranges in measurements varied widely. Differences in polyamine synthesis biomarkers between colposcopically normal and abnormal areas can be demonstrated. However, studies using polyamine synthesis biomarkers in the cervix would require large numbers of patients to achieve significance.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"125-32"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20508890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemoprevention of cancer of uterine cervix: a study on chemoprevention of retinamide II from cervical precancerous lesions.","authors":"C Ruidi,&nbsp;D Aihua,&nbsp;B Peiyu,&nbsp;G Zhongru,&nbsp;L Huazao,&nbsp;S Shifeng,&nbsp;H Rui,&nbsp;X Shiping","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dysplasia of the uterine cervix is a recognized precancerous condition. Because of the observed ability of retinoids to suppress various cell lines in vitro, a number of clinical studies have examined the effect these agents have on cervical dysplasia, with the object of developing a means of chemoprevention of cervical malignancies in women at risk. Three cervical cancer chemoprevention trials with Retinamide II (RII) have been conducted at the Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China. A pilot study used RII to intervene in cases of precancerous cervical dysplasia. Twenty-seven women with mild, moderate, or severe cervical dysplasia, pathologically confirmed, were treated by RII suppositories, 10 mg QD, given intravaginally for 6 months (each course lasting 3 months). The results indicated that after the second course, the overall response rate was 96.29% and the complete response rate was 88.89%. In general, side effects were mild. A little cervical and vaginal irritation was well tolerated. In the second double-blind study, patients with precancerous cervical lesions were randomized into two groups, one treated with RII suppository intravaginally and the other with a placebo, once daily for 50 days in two courses. Precancerous lesions in 68.76% of patients in the treatment arm disappeared, with an overall effective rate of 74.29% after two courses of treatment with RII. Its curative effect was approximately that of laser beam radiation and electrocautery (P > 0.05), and differed significantly (P < 0.01) from that of traditional antiinflammatories. RII can be a major measure in prevention and treatment of cervical cancer in high-incidence areas in China. In the third trial, we are conducting a randomized double-blind study placebo controlled, in a high-incidence area of cervical cancer (Xiang-Yuan county, Shang Xi Province, China). At present, the patients are being followed up and the study will be completed after 2 years.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"140-3"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20508892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colon cancer chemoprevention: clinical development of aspirin as a chemopreventive agent.","authors":"K Krishnan,&nbsp;M T Ruffin,&nbsp;D E Brenner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have studied aspirin as a potential chemopreventive for colorectal cancer, completing Phase I studies on aspirin pharmacology and potential biomarker assays (prostaglandins, PGE2 and PGF2 alpha and cyclooxygenase modulation) in normal human subjects. These studies have determined the optimal dose of aspirin for future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged, detectable even after aspirin and its metabolite are removed from the plasma. Aspirin-mediated inhibition of prostaglandin production in the human rectal epithelium may be related to direct suppression of cyclooxygenase transcription and not to enzyme inactivation by acetylation. A systematic method to monitor adherence (self-report, telephone contact, pill count, and microelectronic monitoring) has been established for future trials. Strategies to improve recruitment of high-risk cohorts have been developed. Phase IIa non-randomized studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5 years, history of colon adenomas > 1 cm, two or more first-degree relatives with colon cancer, and familial adenomatous polyposis and hereditary non-polyposis colorectal cancer syndromes) are currently being conducted for surrogate end-point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and proliferation) modulation.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"148-58"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20508894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Properties of intraepithelial neoplasia relevant to the development of cancer chemopreventive agents.","authors":"C W Boone,&nbsp;J W Bacus,&nbsp;J V Bacus,&nbsp;V E Steele,&nbsp;G J Kelloff","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cancer chemoprevention is concerned with the development of drugs or diet supplements that will avert the onset or stop the progression of the intraepithelial neoplasia which precedes invasive cancer. Two basic processes underlie the onset and development of intraepithelial neoplasia. First is genomic instability (often associated with chronic diffuse epithelial hyperplasia), which is the increased production of genomic structural variants due to unrepaired DNA breaks with secondary formation of abnormal structures, including \"mutator\" mutations in genes responsible for genomic stability, gene copy amplification or loss from DNA breakage-fusion-anaphase bridge cycles, unequal sister chromatid exchange, and accumulation of double minutes. Second is the development within an epithelium having genomic instability of multicentric neoplastic lesions that independently progress through each of the following processes at a continuously accelerating rate: clonal evolution, hyperproliferation, production of genomic structural variants, and apoptosis. Recommended chemoprevention strategies based on these mechanisms are (1) early diagnosis and treatment of genomic instability before the appearance of intraepithelial neoplasia, i.e., during the \"predysplastic\" or \"premorphologic\" phase, (2) development of multiple agents that block intralesional proliferation at steps along the \"command\" pathways of mitotic signal transduction and along the \"execute\" pathways of synthesis of daughter cell components, (3) development of nontoxic antiinflammatory agents, antioxidants, antimutagens, and proapoptotics, (4) avoidance of \"clonal escape\" through use of drug combinations, and (5) use of computer-assisted quantitative image analysis to assay modulation of surrogate endpoints in chemoprevention clinical trials.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20510235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic alterations in mouse lung tumors: implications for cancer chemoprevention.","authors":"C R Herzog,&nbsp;R A Lubet,&nbsp;M You","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Specific genetic alterations affecting known tumor suppressor genes and proto-oncogenes occur during mouse lung tumorigenesis. These include mutational activation of the K-ras gene, commonly seen at a frequency of about 80% in both spontaneously occurring and chemically induced adenomas and adenocarcinomas of the lung, suggesting that it is an early event that persists into malignancy. Allelic loss of the p16 tumor suppressor gene also is a frequent event, occurring in about 50% of mouse lung adenocarcinomas, but rarely in lung adenomas, suggesting that it may play a role in malignant conversion or progression of lung tumors. Other genetic alterations detected in mouse lung tumors include reduced expression of Rb and p16, and increased c-myc expression. Alterations of these genes are also common in the genesis of human lung cancer. Genetic linkage analysis to identify human lung cancer susceptibility genes is difficult due to the genetic heterogeneity and exposure to environmental risk factors. The mouse lung tumor model has become a valuable alternative for identifying such genes. Recently, loci responsible for mouse lung tumor susceptibility have been mapped to chromosomes 6, 9, 17, and 19, while those linked to lung tumor resistance have been mapped to chromosomes 4, 11, 12, and 18. Known candidate susceptibility or resistance genes include the K-ras proto-oncogene on chromosome 6, and the p16 tumor suppressor gene on chromosome 4. With evidence of considerable overlap between the genetic alterations that underlie human and mouse lung tumorigenesis, the mouse lung tumor model has been expanded to include pre-clinical screening of chemopreventive agents against human lung cancer. Studies on the modulation of genetic defects in mouse lung tumors by known and potential chemopreventive agents should further the goal of developing an effective prevention and treatment of lung cancer.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"49-63"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20510238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research and development of cancer chemopreventive agents in China.","authors":"H Rui","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Since the late 1970s, a comprehensive search for cancer chemopreventive agents has been established in our Institute. A series of new retinoids have been synthesized and screened on the basis of established methodologies of experimental chemoprevention in vitro as well as in vivo. Pharmacological studies demonstrated that N-4-(carboxyphenyl)retinamide (RII) induces cell differentiation of HL-60 cells and inhibits dimethylnitrosamine-induced carcinogenesis of the forestomach in mice, 7,12-dimethylbenz[a]anthracene (DMBA)-induced papilloma in mouse skin, and DMBA-induced carcinogenesis of the buccal pouch in Syrian golden hamsters. It significantly promoted lymphoblastic transformation and activated macrophages. In further studies, RII significantly inhibited ornithine decarboxylase activity. After 6 months of chronic toxicological studies in rats and dogs, RII was recommended for clinical trial. Phase II studies found that RII is effective in treating oral and vulvar leukoplakia. It is also effective in treating myelodysplastic syndrome and dysplasia of uterine cervix. The chalcone retinoidal compounds were discovered when the search for new retinoids with less toxicity and higher potency led to third-generation retinoids, which were synthesized and screened. Structure-activity relationship studies found that 3,5-di-tert-butyl-4-methoxy-4-carboxyl chalcone (R9158) is the most active inhibitor of a variety of cancer cells. It has no effect on the Colony Forming Unit-Granulocyte/Macrophage (CFU-GM) of bone marrow in mice. In in vivo studies, R9158 showed a remarkable inhibition of chondrosarcoma in rats. It had no cross-resistance to vincristine, but was cross-resistant to all-trans retinoic acid. Red ginseng, a processed Panax ginseng, is considered a typical tonic in traditional Chinese medicine. Our studies demonstrated that red ginseng extract inhibited DMBA-induced skin papilloma significantly. Experiments showed that glycyrrhetinic acid inhibited croton oil-induced ear edema in mice. It also inhibited epidermal ornithine decarboxylase as well as the rapid DNA damage induced by the carcinogen benzo[a]pyrene (B[a]P). Our pharmacological studies demonstrated that Chinese gallotannin inhibited the malignant transformation of B[a]P-induced V79 cells in vitro and B[a]P-induced pulmonary adenoma in A/J mice in vivo significantly.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"27 ","pages":"7-11"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20511198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interracial comparative study of prostate cancer in the United States, China, and Japan.","authors":"H. Zhau, L. S. Zhao, B. Q. Chen, M. Kojima","doi":"10.1016/S0022-5347(01)62148-7","DOIUrl":"https://doi.org/10.1016/S0022-5347(01)62148-7","url":null,"abstract":"","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 1","pages":"182-5"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0022-5347(01)62148-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55674702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of retinoic acid on HPV titration and colposcopic changes in Korean patients with dysplasia of the uterine cervix.","authors":"W S Ahn,&nbsp;J M Lee,&nbsp;S E Namkoong,&nbsp;H Y Lee,&nbsp;S J Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Retinoids, a family of molecules capable of profound impact on many biological functions, have antiproliferative, differentiative, and immunomodulatory properties. The present study assessed the effect of 13-cis-retinoic acid (13-CRA) treatment in 13 chronic cervicitis and 52 cervical intraepithelial neoplasia patients. We examined low- and high-risk human papilloma virus titer (using the hybrid capture method) and made a colposcopic and cervicographic examination before and after treatment with 13-CRA at 1 mg/kg for 4 to 12 weeks. Patients were between 27 and 64 years, the average age being 36.6 years. Histology revealed chronic cervicitis in 13 cases, mild dysplasia in 18 cases, moderate dysplasia in 18 cases, and severe dysplasia in 16 cases, totaling 65 cases. The expression rate of high-risk human papilloma virus (HPV 16, 18) was 9 of 13 cases (69%) in chronic cervicitis, 7 of 18 cases (38%) in mild dysplasia, 9 of 18 cases (50%) in moderate dysplasia, and 12 of 16 cases (75%) in severe dysplasia, with the overall expression rate being 37 of 65 cases (57%). Following 13-CRA treatment, decreases in high-risk titer were observed in 6 of 9 cases (66%) of chronic cervicitis, 4 of 11 cases (36%) of mild dysplasia, 7 of 9 cases (77%) of moderate dysplasia, and 8 of 12 cases (75%) of severe dysplasia. Overall, HPV titer decreased in 25 of 41 cases (61%). Minimal changes were found in colposcopic and cervicographic observations during the study. In summary, high-risk HPV titer decreased after treatment with 13-CRA in the majority of patients with cervical intraepithelial neoplasia. This study supports the potential of retinoids to interrupt multi-step carcinogenesis, possibly by down-regulation of gene products (E6,E7) produced by HPV infection.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"133-9"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20508891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high-incidence area.","authors":"L D Wang,&nbsp;Q Zhou,&nbsp;C S Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Linxian and the nearby county Huixian, in the Henan province in Northern China, have a very high incidence of esophageal squamous cell carcinoma (SCC). Previous studies from these counties have suggested that increased proliferation of esophageal epithelial cells, morphologically manifested as basal cell hyperplasia (BCH) and dysplasia (DYS), is an early indicator of abnormality in persons predisposed to SCC. A high incidence of gastric cardia adenocarcinoma (AC) was also found in these areas. To determine proliferation patterns of esophageal and gastric cardia epithelia with normal and different severities of precancerous lesions, we measured proliferating cell nuclear antigen (PCNA), Ki-67, and bromodeoxyuridine (BrdU) incorporation and compared the results. Esophageal biopsies (175) and gastric cardia biopsies (41) were collected from symptom-free subjects in Huixian. Of these, 23 esophageal biopsies were incubated with BrdU. The avidin-biotin-peroxidase complex (ABC) method was used to detect PCNA, Ki-67, and BrdU. The number of immunostain-positive cells was counted manually. Intense immunostaining for PCNA, Ki-67, and BrdU was observed in the cell nuclei of tissues with normal and different severities of precancerous lesions. With esophageal biopsies, both PCNA and Ki-67 increased significantly as the epithelia progressed from normal to BCH and to DYS. The number of PCNA- and Ki-67-positive cells was three times higher than that of BrdU incorporation in the same category of BCH. With cardia biopsies, the number of Ki-67 positive cells was lower in normal tissue and increased significantly from chronic superficial gastritis to chronic atrophic gastritis to DYS. Staining patterns for PCNA and Ki-67 were correlated with the histopathology of the esophagus. The correlation was not as clear with gastric cardia. BrdU studies appear to be more complicated. The PCNA and Ki-67 methods may be useful for screening high-risk esophageal and gastric cardia cancer subjects, and for monitoring chemoprevention effects.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"159-65"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20510084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interracial comparative study of prostate cancer in the United States, China, and Japan.","authors":"H E Zhau,&nbsp;L S Zhao,&nbsp;B Q Chen,&nbsp;M Kojima","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The interracial differences of prostate cancer progression have long been documented; however, underlying molecular and cellular mechanisms remain obscure. This study focuses on the histopathologic, immunohistochemical, biochemical, and molecular characterization of prostate cancer tissues unselectively obtained from US, Chinese, and Japanese men. Histopathologic analyses indicate that 74.5% of the prostate cancers in Chinese patients were poorly differentiated, compared with 28.6 and 32.8% of the prostate cancers in US and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. Furthermore, the high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or their geographic origins within China. We found significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7- to 16-fold), but not chromogranin A, in tissue specimens obtained from Chinese prostate cancer patients compared with those from US and Japanese patients. We also found marked differences in p53 protein accumulation among various ethnic groups. The p53 protein was frequently detected in prostate cancer tissue specimens from Chinese (90.2%), but less frequently in US black (3.7%), US white (17.4%), and Japanese (7.1%) men. Further analysis of 31 prostate cancer tissues from Chinese men indicated that mutational changes in the p53 gene occurred between exons 5 and 8.</p>","PeriodicalId":77196,"journal":{"name":"Journal of cellular biochemistry. Supplement","volume":"28-29 ","pages":"182-5"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20510087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}