Synthesis of A83586C/citropeptin hybrid and synthetic studies toward azinothricin

The Azinothricin family of cyclodepsipeptides are a class of antitumour antibiotics whose antitumour properties are attributed to their ability to selectively repress the expression of genes essential for the progression of the cell cycle from G1 to S phase. They have been shown to inhibit E2F transcription factors, which are critical regulators of mammalian cellular proliferation. This biological observation has made them a potentially important new therapeutic target for the control of proliferative diseases, such as cancer. An asymmetric total synthesis of an A83586C-citropeptin hybrid is presented in this thesis, along with a synthetic route to the azinothricin cyclodepsipeptide. The A83586C- citropeptin hybrid will serve as a useful intracellular probe that will provide valuable insights into the mechanism of the antitumour action of this class, which may contribute to a greater understanding of cancer biology. The cyclodepsipeptide components of these molecules have been assembled via a 2+2+2 -fragment condensation strategy and a HATU-mediated macrolactamisation. In the case of the A83586C-citropeptin hybrid, a chemoselective coupling was performed between the fully elaborated N-hydroxybenzotriazole activated ester and the citropeptin cyclodepsipeptide

Incidence Trends of Urinary Bladder and Kidney Cancers in Urban Shanghai, 1973-2005

<div><p>Objectives</p><p>We examined the incidence trends of bladder and kidney cancers using a population-based cancer registration data.</p> <p>Methods</p><p>Age-standardized incidence rates were analyzed using data from the Shanghai Cancer Registry during 1973 to 2005. Annual percentage changes and 95% confidence intervals were calculated to evaluate the incidence changes. Age-period-cohort analysis was further implemented to assess the contributions of age, period and cohort effects to the trends using the intrinsic estimator method.</p> <p>Results</p><p>In total, 12,676 bladder and 5,811 kidney cancer patients were registered in urban Shanghai. The age-standardized rates of bladder cancer in males increased from 6.39 to 7.66 per 100,000, or 0.62% per year, whereas the rates in females increased from 1.95 to 2.09 per 100,000, or 0.33% per year. For kidney cancer, the age-standardized rates in males increased from 1.20 to 5.64 per 100,000, or 6.98% per year. Similarly in females, the rates increased from 0.85 to 3.33 per 100,000, or 5.93% per year. Age-period-cohort analysis showed increasing curves of age and period effects but generally decreasing cohort effects for bladder and kidney cancers. </p> <p>Conclusions</p><p>Our results show increasing incidence trends of bladder and kidney cancers in Chinese men and women, especially for kidney cancer.</p> </div

Forest plot of obesity and risk of bladder cancer.

<p>Squares indicate study-specific relative risks (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines represent 95% CIs; the diamond indicates the summary relative risk estimate with its 95% CI. CI, confidence interval.</p

Trends in incidence rates of cancers of bladder and kidney in urban Shanghai, 1973-2005.

<p>Trends in incidence rates of cancers of bladder and kidney in urban Shanghai, 1973-2005.</p

Forest plot of preobese and risk of bladder cancer.

<p>Squares indicate study-specific relative risks (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines represent 95% CIs; the diamond indicates the summary relative risk estimate with its 95% CI. CI, confidence interval.</p

Dose-response relationships between body mass index and the relative risk of bladder cancer.

<p>Shaded area represents 95% confidence limits for fitted curve. <i>P</i> = 0.467 for non-linearity, which indicates no curvilinear association.</p

Flow diagram of the study selection for the meta-analysis.

<p>Flow diagram of the study selection for the meta-analysis.</p

Associations between types of physical activity and T2DM risk.

*<p>Model 1: Adjusted for age at interview, energy intake, smoking, alcohol consumption, education level, occupation, income level, hypertension, and family history of diabetes.</p>**<p>Model 2: As above plus BMI and WHR.</p>***<p>Analysis restricted to employed participants.</p

Associations between cigarette smoking and T2DM risk.

*<p>Model 1: Adjusted for age, energy intake, total physical activity METs, alcohol consumption, education level, occupation, income level, hypertension, and family history of diabetes.</p>**<p>Model 2: As above plus BMI and WHR.</p

Demographic characteristics of participants by T2DM status.

<p>T-tests were used for continuous variables; chi-square tests were used for categorical variables.</p