Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.

Associations of Serum Isoflavone, Adiponectin and Insulin Levels with Risk for Epithelial Ovarian Cancer: Results of a Case-control Study.

BACKGROUND: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. MATERIALS AND METHODS: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. RESULTS: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (Ptrend<0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (Ptrend=0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (Ptrend=0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low Ptrend<0.001). CONCLUSIONS: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

Relationship of serum isoflavone, insulin and adiponectin levels with breast cancer risk.

BACKGROUND: Obesity is one of the well-known risk factors of breast cancer. Accumulating evidence suggests that adiponectin, an obesity-related hormone, is inversely associated with breast cancer risk, particularly in postmenopausal women. Obesity is also associated with high levels of insulin. In addition, studies have suggested that the soy isoflavones present in the traditional Japanese diet have been associated with decreased risk of breast cancer. However, there is no study that has assessed associations between serum levels of isoflavones, insulin, adiponectin and the risk of breast cancer all together with menopausal status. METHODS: In a case-control study of 63 histologically confirmed breast cancer patients and 76 controls, serum isoflavone, insulin, and high-molecular-weight (HMW) adiponectin levels and breast cancer risk were examined for their association with breast cancer risk after adjustment for various risk factors. RESULTS: Women in the highest tertile of serum HMW adiponectin levels were associated with a statistically significant decreased risk for breast cancer compared with women in the lowest tertile [odds ratio (OR), 0.09; 95 % confidence interval (CI) 0.03-0.33]. This association was observed in postmenopausal women (OR 0.06; 95 % CI 0.01-0.28), but not in premenopausal women. The observed associations were independent of possible effects of insulin, body mass index, and known risk factors for breast cancer. Serum isoflavones and insulin levels were not associated with breast cancer risk. CONCLUSIONS: This study suggests that high serum HMW adiponectin levels are significantly associated with a decreased risk for breast cancer. Our result support the hypothesis that serum adiponectin may act as a potential biomarker for breast cancer.

Relation of serum adiponectin levels and obesity with breast cancer: a Japanese case-control study.

BACKGROUND: It is known that obesity is one of the risk factors for breast cancer although the association may differ between ethnic groups and with the menopausal status. Recently obesity-related risk factors including serum adiponectin and insulin levels have been analyzed together with BMI in association with breast cancer risk. MATERIALS AND METHODS: We measured serum high molecular weight (HMW) adiponectin and insulin levels in a hospital based case-control study, including 66 sets of Japanese female breast cancer cases and age and menopausal status matched controls. Serum levels of HMW adiponectin, insulin levels and body mass index (BMI) were examined in association with breast cancer risk with adjustment for the various known risk factors by menopausal status. RESULTS: Women in the highest HMW adiponectin levels showed significant reduced risk of breast cancer in both pre and postmenopausal women (odds ratio (OR), 0.01; 95% confidence interval (CI), 0.00-0.26 and 0.13; 0.03-0.57, respectively). Lower BMI showed decreased breast cancer risk in both pre and postmenopausal women (OR, 0.04; 95% CI, 0.00-0.69, OR, 0.28; 95% CI, 0.07-1.11, respectively). CONCLUSIONS: These results indicated that higher serum HMW adiponectin levels and lower BMI are associated with a decreased breast cancer risk in both pre and postmenopausal women in Japan, adding evidence for the obesity link.

Equol, adiponectin, insulin levels and risk of breast cancer.

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death among women. Soy isoflavones have been widely studied and among all isoflavones equol has been gaining interest with regard to its relationship with breast cancer risk. Obesity has been revealed as one of the breast cancer risk factors, known to be associated with high levels of circulating insulin and decreased levels of adiponectin. Hence there have been many studies investigating relationships between insulin and adiponectin levels and breast cancer risk. Additionally recent findings have suggested that insulin and adiponectin themselves may have influence on breast cancer development, independent of obesity. In the present review, we discuss the relationships between breast cancer risk and equol, insulin and adiponectin levels, which are three important factors in our ongoing hospital-based case-control study. Herein these factors are reviewed not only from the clinical viewpoint but also from possible chemical and biological points of view which may explain clinical observations.

Interaction between ESRα polymorphisms and environmental factors in osteoporosis.

We hypothesized that environmental factors might affect the relationship between genetic predisposition and the risk of bone mineral density (BMD) loss. Cases were 114 Japanese women with a confirmed diagnosis of postmenopausal osteoporosis and controls were 171 general Japanese women. Genetic risk of SNPs in the estrogen receptors was analyzed by a case-control study. The interaction between gene and environmental factors for osteoporosis were assessed by a case-only design. Significant increases in osteoporosis risk were observed with minor alleles of rs2077647 located in the first exon and rs2234693 located in the first intron of estrogen receptor α (ESRα). Haplotype CC at these risk SNPs was strongly associated with osteoporosis risk (odds ratio [OR] = 3.15, 95% confidence interval [CI] = 1.83-5.41). There was a statistically significant interaction between haplotype CC and alcohol drinking; moderate alcohol consumption decreased genetic risk of osteoporosis (OR = 0.22, 95%CI = 0.05-0.83).

Relationship between hepatocellular carcinoma and impaired glucose tolerance among Japanese.

BACKGROUND/AIMS: Both the incidence of diabetes mellitus (DM) and mortality from Hepatocellular carcinoma (HCC) are increasing in Japan. As the association of overall cancer and HCC with impaired glucose tolerance (IGT) has been studied rarely in the world including Japan, this study assessed their associations using cohort data of Hokkaido, Japan. METHODOLOGY: After getting ethical consent, this study included 908 men and 1,081 women aged 30-77 years during 1977-78 and collected detailed information using the baseline survey. The subjects were followed until 2002 and deaths were recorded using ICD-9. Classifying them into three groups of diabetes status namely DM, IGT, and normal, the relative risk (RR) of mortality was estimated by diabetes status using multivariate Cox model. RESULTS: This study revealed no association between overall cancer and diabetes status. However, the RR of mortality from HCC was about 11 times (HR= 10.8, 95%CI: 1.3-92.5) higher in IGT compared with normal group. DM group also showed higher risk of mortality than normal group. CONCLUSIONS: HCC mortality was significantly high among IGT group. However, as the results of the study were based on small data, further studies with large cohort are needed to address the association of IGT with overall cancer and HCC mortality in Japan.

Wnt3 modulates the characteristics and cobblestone area-supporting activity of human stromal cells.

OBJECTIVE: Our objective was to investigate the expression and significance of Wnt proteins in adult human hematopoietic-supporting stromal cells. METHODS: Degenerate reverse transcription-polymerase chain reaction was performed to screen telomerized human stromal cells (hTERT-stromal cells) and multipotent mesenchymal cells (hTERT-MSCs) for expression of Wnt genes. We studied the actions of Wnt proteins by overexpressing them in stromal cells and MSCs by retrovirus-mediated gene transfer. RESULTS: The hTERT-stromal and primary stromal cells expressed Wnt5A, while hTERT-MSCs and primary MSCs expressed Wnt3 and Wnt5A. Gene transfer of Wnt5A slightly reduced the growth rate of hTERT-stromal cells, but did not affect their morphology. In contrast, gene transfer of Wnt3 into both hTERT-stromal cells and hTERT-MSCs enhanced Wnt-betacatenin signaling, and caused remarkable morphological changes and growth retardation. Upon 2-week co-culture, expansion of clonogenic cells on Wnt5A-stromal cells was superior to that on control stromal cells. However, expansion of CD34+ cells on Wnt3-stromal cells did not differ from that on control stromal cells. Moreover, there was a drastic reduction in the formation of cobblestone area (CA) underneath Wnt3-stromal cells compared with that underneath control stromal cells. CONCLUSION: These results suggest that Wnt3 plays an important role in regulating characteristics and CA support activity of stromal cells.