Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Eur J Cancer Prev ; 33(1): 62-68, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37477151

ABSTRACT

BACKGROUND: While timely assessment of long-term survival in thyroid cancer patients is critical for assessing early detection and screening programs for thyroid cancer, those data are sorely lacking in China. We aimed to timely and accurately assess the long-term survival of thyroid cancer patients in eastern China. METHODS: Patients diagnosed with thyroid cancer during 2004-2018 from four cancer registries in Taizhou, eastern China were included. The 5-year relative survival was estimated by period analysis and stratified by sex, age at diagnosis, and region. The 5-year RS of thyroid cancer patients during 2019-2023 was also predicted using the model-based period analysis. RESULTS: During 2014-2018, the overall 5-year relative survival of thyroid cancer patients was 87.7%, 91.2% for women and 79.4% for men. The 5-year RS decreased along with increasing age at diagnosis, decreasing from 94.9% for age <45 years to 81.3% for age >74 years, while 5-year RS was higher in urban areas than in rural areas (93.2% vs. 86.1%). The 5-year RS for thyroid cancer patients improved greatly between 2004-2008 to 2014-2018. The predicted overall 5-year RS could reach 91.4% over the upcoming 2019-2023 period. CONCLUSION: We provided, for the first time in China using period analysis, the most up-to-date 5-year RS for thyroid cancer patients from Taizhou, eastern China, which has important implications for timely evaluation on early detection and screening programs for patients with thyroid cancer in eastern China.


Subject(s)
Thyroid Neoplasms , Male , Humans , Female , Middle Aged , Aged , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/epidemiology , Registries , China/epidemiology , Demography , Survival Analysis
2.
BMC Cancer ; 23(1): 642, 2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37430229

ABSTRACT

Assessing long-term tumor survival rates is crucial for evaluating the effectiveness of tumor treatment and burden. However, timely assessment of long-term survival in patients with pancreatic cancer is lagging in China. In this study, we applied period analysis to estimate the long-term survival of pancreatic cancer patients using data from four population-based cancer registries in Taizhou city, eastern China. A total of 1121 patients diagnosed with pancreatic cancer between 2004 and 2018 were included. We assessed the 5-year relative survival (RS) using period analysis and further stratified by sex, age at diagnosis, and region. The 5-year RS during 2014-2018 overall reached 18.9% (14.7% for men and 23.3% for women, respectively). A decrease of the 5-year RS from 30.3% to 11.2% was observed in four diagnostic age gradients (< 55, 55-64, 65-74, and > 74 years age groups). The 5-year RS was higher in urban (24.2%) than in rural (17.4%) areas. Moreover, the 5-year RS of pancreatic cancer patients showed an overall increasing trend for the three periods (2004-2008, 2009-2013, and 2014-2018). Our study, using period analysis for the first time in China, provides the latest estimates of the survival of patients with pancreatic cancer, which provides essential evidence for the prevention and intervention of pancreatic cancer. The results also indicate the importance of further applications of the period analysis for more up-to-date and accurate survival estimates.


Subject(s)
Pancreatic Neoplasms , Male , Humans , Female , Aged , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/therapy , China/epidemiology , Patients , Demography , Pancreatic Neoplasms
4.
J Clin Med ; 12(10)2023 May 16.
Article in English | MEDLINE | ID: mdl-37240586

ABSTRACT

OBJECTIVE: Ovarian cancer is a deadly gynecologic malignancy with a poor prognosis. It is essential to evaluate the early detection and screening programs of ovarian cancer via timely assessment of long-time survival, particularly in China where those data are incredibly limited. Here, we aimed to provide timely and accurately assessment of long-term survival estimate of ovarian cancer patients from eastern China. METHODS: Data of 770 ovarian cancer patients diagnosed between 2004-2018 were obtained from four cancer registries in Taizhou, eastern China, were included. We used period analysis to calculate five-year relative survival (RS) of aforementioned ovarian cancer patients for overall and the stratification by age at diagnosis and region. RESULTS: Our findings demonstrated that the overall five-year RS for ovarian cancer patients in Taizhou between 2014 and 2018 was 69.2%, while urban areas were higher compared to rural areas (77.6% vs. 64.9%). We also observed a significant age gradient with the five-year RS decreasing from 79.6% for age group < 55 years to 66.9% for age group > 74 years. Furthermore, we identified a clear upward trend of five-year RS over the study period, both overall and stratified by region and age at diagnosis. CONCLUSION: This is the first study in China using period analysis to provide the most up-to-date five-year RS for ovarian cancer patients from Taizhou, eastern China, which reaches 69.2% during 2014-2018. Our results provide valuable information for timely assessment of early detection and screening programs for ovarian cancer in eastern China.

5.
Cancer Med ; 12(3): 3696-3704, 2023 02.
Article in English | MEDLINE | ID: mdl-36065512

ABSTRACT

INTRODUCTION: While timely assessment of long-term survival for patients with colorectal cancer (CRC) is essential for evaluation on early detection and screening programs of colorectal cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for CRC patients in eastern China. METHODS: Patients diagnosed with CRC during 2004-2018 and followed up until December 31, 2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for overall and the stratification by sex, age at diagnosis and region. The projected 5-year RS of CRC patients during 2019-2023 was also assessed using a model-based period analysis. RESULTS: Overall 5-year RS for patients with CRC during 2014-2018 reached 78.8%, being 74.9% for men and 86.1% for women. 5-year RS declined along with aging, decreasing from 84.1% for age < 45 years to 48.9% for age > 74 years, while 5-year RS for urban area was higher compared to rural area (83.9% vs. 75.8%). Projected overall 5-year RS of CRC patients could reach 85.9% during the upcoming period 2019-2023. CONCLUSIONS: We provided, for first time in China using period analysis, most up-to-date 5-year RS for patients with CRC from Taizhou, eastern China and also found 5-year RS for CRC patients have improved greatly during 2004-2018.


Subject(s)
Colorectal Neoplasms , Male , Humans , Female , Middle Aged , Aged , Aging , China , Registries , Demography
6.
Journal of Preventive Medicine ; (12): 916-920, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-997155

ABSTRACT

Objective@#To investigate the level of chronic disease prevention and control literacy and its influencing factors among residents in Taizhou City, Zhejiang Province, so as to provide insights into formulating health education strategies on chronic diseases. @*Methods@#A total of 32 313 permanent residents at ages of 15 to 69 years were sampled in Taizhou City using the multi-stage stratified random sampling method and probability proportionate to size sampling method (PPS). Subjects' demographic characteristics and chronic disease prevention and control literacy were collected using the national health literacy surveillance questionnaire. The levels of chronic disease prevention and control literacy from 2017 to 2022 were evaluated and standardized by the population data provided by Taizhou Municipal Bureau of Statistics. Factors affecting the chronic disease prevention and control literacy were identified using a multivariable logistic regression model. @*Results@#Totally 32 313 questionnaires were distributed, and 32 258 valid questionnaires were recovered, with an effective recovery rate of 99.83%. The median age of participants was 51.00 (interquartile range, 19.00) years. There were 15 754 men (48.84%) and 16 504 women (51.16%), and 11 060 urban residents (34.29%) and 21 198 rural residents (65.71%). Farmer was the predominant occupation (16 003 residents, 49.61%). The level of chronic disease prevention and control literacy among residents in Taizhou City was 32.97%, which was 22.58%, 26.41%, 33.48%, 34.44%, 38.53% and 39.68% from 2017 to 2022, respectively, showing an upward trend (P<0.05) with a cumulative growth rate of 17.10%. Multivariable logistic regression analysis showed that age (15 to 24 years, OR=1.566, 95%CI: 1.309-1.874; 25 to 34 years, OR=1.345, 95%CI: 1.173-1.542; 35 to 44 years, OR=1.482, 95%CI: 1.311-1.675; 45 to 54 years, OR=1.203, 95%CI: 1.078-1.343), educational level (primary school, OR=1.728, 95%CI: 1.546-1.932; junior high school, OR=2.211, 95%CI: 1.977-2.472; high school/vocational high school/technical secondary school, OR=3.368, 95%CI: 2.972-3.817; college or above, OR=7.271, 95%CI: 6.313-8.373), occupation (farmer, OR=0.739, 95%CI: 0.663-0.825; others, OR=0.778, 95%CI: 0.694-0.872), place of residence (urban areas, OR=0.903, 95%CI: 0.852-0.956) and annual household income (30 000 to 49 999 Yuan, OR=1.138, 95%CI: 1.030-1.259; 50 000 to 99 999 Yuan, OR=1.239, 95%CI: 1.143-1.342; 100 000 to 199 999 Yuan, OR=1.445, 95%CI: 1.334-1.566; 200 000 Yuan and above, OR=1.803, 95%CI: 1.629-1.997) were influencing factors for chronic disease prevention and control literacy. @* Conclusions @#The level of chronic disease prevention and control literacy among residents in Taizhou City shows an upward trend from 2017 to 2022, with age, educational level, occupation, place of residence and annual household income as the influencing factors.

7.
Chinese Journal of School Health ; (12): 348-352, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965855

ABSTRACT

Objective@#To explore the effectiveness of healthy school canteen intervention on nutritional literacy, food consumption, as well as attitude towards school canteen.@*Methods@#A primary school in Taizhou City was selected as the intervention school, and another comparable primary school was selected as the control one. A total of 320 students (163 in the intervention group and 157 in the control group) received a comprehensive intervention based on the construction of a healthy school canteen in the school,incluling healthy dining environment,food impravement,chef training,nutrition and health education, while the control group did not receive any intervention. Questionnaires survey was administered to both groups before and after the intervention.@*Results@#Before the intervention, no significant differences were found in the total scores of skills and nutrition literacy, frequency of food intake, behaviors and attitudes related to canteen construction between the two groups( P >0.05). Daily intake of vegetables, dairy products, fish/poultry/eggs/lean meat increased by 19.63, 15.95 and 19.63 percentage point respectively ( χ 2=15.25,9.14,13.93, P <0.01). The proportion of students reporting have read related intervention materials in the intervention group(95.71%) was higher than the control group(84.71%) ( χ 2= 11.04, P < 0.01 ). The students in favor of low salt, low oil and low sugar dishes in the intervention group (74.85%) was higher than in the control group(48.41%) ( χ 2=23.73, P <0.01).@*Conclusion@#Based on the comprehensive intervention of nutrition and health canteens can improve students nutrition literacy and dietary structure. It is recommended to adopt the form of "home school linkage" to carry out the construction of large sample, multi regional and long term nutrition and health canteens.

8.
Front Oncol ; 12: 998641, 2022.
Article in English | MEDLINE | ID: mdl-36578940

ABSTRACT

Objectives: While timely assessment of long-term survival for patients with breast cancer is essential for evaluation on early detection and screening programs, those data are extremely scant in China. We aimed to derive most up-to-date survival estimates and to predict future survival using the cancer registry data from Taizhou city, Eastern China. Methods: Patients diagnosed with breast cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for the overall population and according to the stratification factors sex, age at diagnosis and geographic region. We further predict the upcoming 5-year RS during 2019-2023, using continuous data from three 5-year periods (2004-2008, 2009-2013 and 2014-2018) and a model-based period approach. Results: Overall 6159 patients diagnosed with breast cancer during 2004-2018 were enrolled. The 5-year RS for breast cancer in 2014-2018 reached 88.8%, while women were higher compared to men (90.5% versus 83.7%) and urban areas were higher compared to rural areas (91.9% versus 86.7%). Additionally, we found a clear gradient by age at diagnosis, ranging from 94.8% for age<45 years to 83.3% for age>74 years. Projected overall 5-year RS for the upcoming 2019-2023 could reach 91.5% (84.8% for men and 93.5% for women). Conclusions: We provided, for first time in China, using period analysis, most up-to-date 5-year RS (88.8%) for patients with breast cancer from Taizhou, Eastern China. We also demonstrate the 5-year RS has improved greatly over last 15 years, which has important implications for timely evaluation of early detection and screening programs.

9.
Front Public Health ; 10: 926058, 2022.
Article in English | MEDLINE | ID: mdl-35958852

ABSTRACT

Objectives: While timely assessment of long-term survival for patients with cervical cancer is essential for the evaluation of early detection and screening programs for cervical cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for patients with cervical cancer in eastern China, using cancer registry data from Taizhou, eastern China. Methods: Patients diagnosed with cervical cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. A period analysis was used to calculate the 5-year relative survival (RS) overall and on stratification by sex, age at diagnosis, and region. Additionally, the projected 5-year relative survival (RS) of patients with cervical cancer during 2019-2023 was evaluated, using a model-based period analysis. Results: Overall 5-year RS for patients with cervical cancer during 2014-2018 reached 90.9%. When stratified by age at diagnosis, we found a clear age gradient for 5-year RS, declining from 95.6% for age <45 years to 68.7% for age >74 years, while urban areas had higher 5-year RS compared to rural areas (92.9 vs. 88.6%). We found a clear increasing trend of 5-year RS during 2004-2018 overall and on stratification by region and age at diagnosis. The projected overall 5-year RS is expected to reach 94.2% for the period 2019-2023. Conclusions: We found that, for the first time in China, using period analysis, the most up-to-date (during 2014-2018) 5-year RS for patients with cervical cancer reached 90.9%. Our data have important implications for the timely evaluation of early detection and screening programs for patients with cervical cancer in eastern China.


Subject(s)
Uterine Cervical Neoplasms , Aged , Child, Preschool , China/epidemiology , Demography , Female , Humans , Mass Screening , Registries , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control
10.
Front Oncol ; 12: 920094, 2022.
Article in English | MEDLINE | ID: mdl-35860562

ABSTRACT

Introduction: While timely assessment of long-term survival for patients with liver cancer is essential for the evaluation of early detection and screening programs of liver cancer, those data are extremely scarce in China. We aimed to timely and accurately assess long-term survival for liver cancer patients in eastern China. Methods: Patients diagnosed with liver cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, eastern China, were included. The period analysis was used to calculate the 5-year relative survival (RS) for overall and the stratification by sex, age at diagnosis, and region. The projected 5-year RS of liver cancer patients during 2019-2023 was also assessed using a model-based period analysis. Results: The overall 5-year RS for patients with liver cancer during 2014-2018 reached 32.4%, being 29.3% for men and 36.1% for women. The 5-year RS declined along with aging, decreasing from 38.2% for age <45 years to 18.8% for age >74 years, while the 5-year RS for urban area was higher compared to rural area (36.8% vs. 29.3%). The projected overall 5-year RS of liver cancer patients could reach 41.4% during the upcoming period 2019-2023. Conclusions: We provided, for first time in China using the period analysis, the most up-to-date 5-year RS for patients with liver cancer from Taizhou, eastern China, and also found that the 5-year RS for liver cancer patients have improved greatly during 2004-2018, which has important implications for the timely evaluation of early detection and screening programs for patients with liver cancer in eastern China.

11.
J Clin Lab Anal ; 36(5): e24356, 2022 May.
Article in English | MEDLINE | ID: mdl-35318741

ABSTRACT

BACKGROUND: The aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio, which is used to measure liver injury, has been found to be associated with some chronic diseases and mortality. However, its relevance to cancer incidence resulting from population-based prospective studies has rarely been reported. In this study, we investigated the correlation of the AST/ALT ratio as a possible predictor of mortality and cancer incidence. METHODS: A total of 9,946 participants fulfilled the inclusion criteria for a basic public health service project of the Health Checkup Program conducted by the BaiYun Community Health Service Center, Taizhou. Deceased participants and cancer incident cases were from The Taizhou Chronic Disease Information Management System. Odds ratios (ORs) and interval of quartile range (IQR) computed by logistic regression analysis and cumulative incidence rate were calculated by the Kaplan-Meier survival method and compared with log-rank test statistics. RESULTS: Serum ALT and AST levels were both increased in patients with chronic diseases, but the ratio of AST/ALT was generally decreased. The cancer incident cases (488 new cases) had a greater baseline ratio (median =1.23, IQR: 0.96-1.54) than noncancer cases (median =1.15, IQR: 0.91-1.44). Compared to the first quartile of the AST/ALT ratio, the population in the top quartile had a higher cumulative cancer incidence rate (7.54% vs. 4.44%) during follow-up period. Furthermore, an elevated AST/ALT ratio increased the risk of all-cause mortality. CONCLUSIONS: The ratio of AST/ALT is a potential biomarker to assess healthy conditions and long-term mortality. Especially for cancer, the AST/ALT ratio not only increases at baseline but also predicts the future development of cancer. The clinical value and potential mechanism deserve further research.


Subject(s)
Liver Diseases , Neoplasms , Alanine Transaminase , Aspartate Aminotransferases , Humans , Neoplasms/epidemiology , Prospective Studies
12.
Front Oncol ; 11: 661012, 2021.
Article in English | MEDLINE | ID: mdl-34046354

ABSTRACT

BACKGROUND: The assessment of long-term survival of lung cancer patients based on data from population-based caner registries, using period analysis, was scarce in China. We aimed to accurately assess the long-term survival of lung cancer patients, and to predict the long-term survival in the future, using cancer registry data from Taizhou City, eastern China. METHODS: Four cancer registries with high-quality data were selected. Patients diagnosed with lung cancer during 2004-2018 were included. The long-term survival was evaluated using period analysis, with further stratification by sex, age at diagnosis and region. Additionally, projected 5-year relative survival (RS) of lung cancer patients for 2019-2023 was evaluated, using model-based period analysis. RESULTS: The 5-year RS of lung cancer patients diagnosed during 2014-2018 was 40.2% (31.5% for men and 56.2% for women). A moderate age gradient was observed for the period estimate, with the estimate decreasing from 50.5 to 26.5% in the age group of 15-44 years and ≥75 years, respectively. The 5-year RS of urban area was higher than that of rural area (52.3% vs. 38.9%). The overall projected 5-year RS of lung cancer patients was 52.7% for 2019-2023, with estimate of 43.0 and 73.2% for men and women, respectively. A moderate age gradient was also observed for the projected estimate. Moreover, estimate reached nearly 50% for rural and urban areas. CONCLUSION: Period analysis tended to provide the up-to-date and precise survival estimates for lung cancer patients, which is worth further application, and provides important evidence for prevention and intervention of lung cancer.

13.
Int J Cancer ; 147(4): 996-1005, 2020 08 15.
Article in English | MEDLINE | ID: mdl-31943167

ABSTRACT

We aimed to provide a systematical evaluation of the performance of period analysis compared to traditional cohort and complete methods, using cancer registry data from Taizhou, eastern China. Overall, 5-year relative survival (RS) estimate was calculated using cohort analysis, complete analysis and period analysis, respectively; further analyses were stratified by sex, region, age at diagnosis and cancer sites. Deviation value (DV), defined as the deviation between the estimated 5-year RS obtained from each method and the observed actual survival, was calculated to evaluate the accuracy of each method. Overall, 5-year RS derived by period analysis were much closer to the observed actual survival (51.4%), compared to those by complete and cohort methods, with the estimates of 48.7% (DV: -2.7%), 43.2% (DV: -8.2%) and 36.3% (DV: -15.1%), respectively. Further stratifications by sex, age at diagnosis, region and cancer sites also supported period analysis provided more precise estimates, compared to complete and cohort methods. We found, for first time systematically using cancer registry data from eastern China, period analysis provided more up-to-date precise estimates of long-term survival for overall and stratifications by sex, age at diagnosis, region and cancer sites, compared to traditional cohort and complete methods. Nevertheless, further investigations using large cancer registry data across China are warranted for the widespread use of period analysis in China.


Subject(s)
Neoplasms/epidemiology , Registries/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Neoplasms/classification , Neoplasms/mortality , Survival Analysis , Survival Rate , Young Adult
14.
Environ Sci Technol ; 47(6): 2654-60, 2013 Mar 19.
Article in English | MEDLINE | ID: mdl-23398278

ABSTRACT

Improved methods are required for the recycling of waste printed circuit boards (WPCBs). In this study, WPCBs (1-1.5 cm(2)) were separated into their components using dimethyl sulfoxide (DMSO) at 60 °C for 45 min and a metallographic microscope was used to verify their delamination. An increased incubation time of 210 min yielded a complete separation of WPCBs into their components, and copper foils and glass fibers were obtained. The separation time decreased with increasing temperature. When the WPCB size was increased to 2-3 cm(2), the temperature required for complete separation increased to 90 °C. When the temperature was increased to 135 °C, liquid photo solder resists could be removed from the copper foil surfaces. The DMSO was regenerated by rotary decompression evaporation, and residues were obtained. Fourier transform infrared spectroscopy (FT-IR), thermal analysis, nuclear magnetic resonance, scanning electron microscopy, and energy-dispersive X-ray spectroscopy were used to verify that these residues were brominated epoxy resins. From FT-IR analysis after the dissolution of brominated epoxy resins in DMSO it was deduced that hydrogen bonding may play an important role in the dissolution mechanism. This novel technology offers a method for separating valuable materials and preventing environmental pollution from WPCBs.


Subject(s)
Dimethyl Sulfoxide/chemistry , Epoxy Resins/chemistry , Recycling/methods , Copper/chemistry , Electronics/instrumentation , Glass/chemistry , Halogenation , Solubility , Temperature
15.
Cancer Res ; 68(11): 4377-83, 2008 Jun 01.
Article in English | MEDLINE | ID: mdl-18519699

ABSTRACT

Patients with hormone-refractory prostate cancer (HRPC) have an estimated median survival of only 10 months because of acquired drug resistance, urging the need to develop therapies against the drug-resistant HRPC phenotype. Accumulating evidence suggests that overexpressing antiapoptotic Bcl-2 family proteins is at least partially responsible for the development of drug resistance among HRPC patients. Antagonizing the antiapoptotic Bcl-2 family proteins, therefore, is one potential approach to circumventing drug resistance in HRPC. WL-276 was developed as a small-molecule antagonist against antiapoptotic Bcl-2 family proteins, with binding potency comparable to (-)-gossypol. Overexpressing Bcl-2 or Bcl-X(L) failed to confer resistance to WL-276. WL-276 also effectively induced apoptosis in PC-3 cells. In addition, three PC-3 cell lines with acquired drug resistance against standard cancer chemotherapies were more sensitive to WL-276 than the parent PC-3 cell line. The increased cytotoxicity toward drug-resistant PC-3 cells shows the clinical potential of WL-276 against HRPC that is resistant to conventional therapies. The anticancer activity of WL-276 was manifested in its suppression of PC-3-induced prostate tumor growth in vivo. The selective toxicity of WL-276 against drug-resistant PC-3 cells and its in vivo suppression of PC-3 prostate tumor growth suggest that WL-276 is a promising lead candidate for the development of Bcl-2 antagonists against drug-resistant HRPC.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Division/drug effects , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Sulfonamides/pharmacology , Thiazoles/pharmacology , Animals , Apoptosis , Cell Line, Tumor , Drug Resistance, Neoplasm , Humans , Male , Mice , Mice, Nude
16.
Bioorg Med Chem Lett ; 18(1): 236-40, 2008 Jan 01.
Article in English | MEDLINE | ID: mdl-18023349

ABSTRACT

Bcl-2 family proteins can be classified into two subfamilies--anti-apoptotic members and pro-apoptotic members. Mechanistically, these two subfamilies can antagonize each other through heterodimerization while homodimerization has been proposed for each subfamily to carry out their corresponding anti-apoptotic or pro-apoptotic functions. To date, many small-molecule antagonists against anti-apoptotic Bcl-2 proteins have been developed, which are monomeric modulators. In this study, a series of BH3I-1 based dimeric modulators were developed with structure-activity relationship explored. Dimeric modulators compared to the monomeric antagonists have enhanced binding activity against anti-apoptotic Bcl-2 proteins. In addition, the acidic functional group was demonstrated to be critical for the binding interaction of the small-molecule antagonists with anti-apoptotic Bcl-2 proteins. Finally, the representative dimeric modulator revealed enhanced activity in inducing cytochrome c release from mitochondria compared to its monomeric counterpart. Taken together, dimerization of monomeric modulators is one practical approach to enhance the bioactivity of Bcl-2 antagonists.


Subject(s)
Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Thiazoles/chemistry , Thiazoles/pharmacology , Apoptosis/drug effects , Apoptosis/physiology , Dimerization , Kinetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Structure-Activity Relationship , Thiazoles/chemical synthesis , Thiazoles/metabolism , Thiazolidinediones , bcl-X Protein/antagonists & inhibitors , bcl-X Protein/metabolism
17.
Bioorg Med Chem ; 15(5): 2167-76, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17227711

ABSTRACT

A series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were synthesized and their binding interactions with Bcl-2, Bcl-X(L), and Bcl-w were evaluated. It was found that modification of BHI-1 resulted in varied binding profiles among Bcl-2, Bcl-X(L), and Bcl-w, and a set of inhibitors with varied selectivity to Bcl-2, Bcl-X(L), and Bcl-w proteins have been identified. Molecular modeling of the interaction of the BHI-1 based analogues with the anti-apoptotic Bcl-2 proteins suggested that the binding site for the BHI-1 based inhibitor was the least conserved section among Bcl-2, Bcl-X(L), and Bcl-w: targeting the non-conserved section may account for the observed selectivity of the BHI-1 based inhibitors among the anti-apoptotic Bcl-2 proteins. The validity of the model was supported by a strong correlation between the model-calculated binding energy and the experimental binding affinity. In summary, our studies suggest that most of the reported inhibitors for anti-apoptotic Bcl-2 proteins are nonselective and BHI-1 is a promising template to distinguish among Bcl-2, Bcl-X(L), and Bcl-w by targeting the non-conserved domain among the anti-apoptotic Bcl-2 proteins. Molecular-modeling-aided rational development of BHI-1 based selective inhibitor for anti-apoptotic Bcl-2 proteins is underway.


Subject(s)
Apoptosis , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Amino Acid Sequence , Fluorescence Polarization , Models, Molecular , Molecular Sequence Data , Recombinant Proteins/antagonists & inhibitors , Spectrometry, Mass, Electrospray Ionization
18.
Drug Metab Lett ; 1(3): 232-40, 2007 Aug.
Article in English | MEDLINE | ID: mdl-19356048

ABSTRACT

Site-specific mono-PEGylations were performed in different conformational regions of Thymosin alpha 1 (T alpha 1) by introducing one cysteine residue into the chosen site and coupling with thiol-specific mPEG-MAL reagent. Results demonstrated that PEGylated sites and regions influenced the conformations and pharmacokinetic profiles of the peptide greatly with following order: alpha-helix, beta-turn, random coil and terminals, but little on the immunoactivity.


Subject(s)
Adjuvants, Immunologic/pharmacokinetics , Maleimides/chemistry , Polyethylene Glycols/chemistry , Thymosin/analogs & derivatives , Adjuvants, Immunologic/chemistry , Animals , Cell Proliferation/drug effects , Mice , Mice, Inbred BALB C , Protein Conformation , Spleen/cytology , Spleen/drug effects , Spleen/immunology , Thymalfasin , Thymosin/chemistry , Thymosin/pharmacokinetics
SELECTION OF CITATIONS
SEARCH DETAIL
...