Uterine sutures at prior caesarean section and placenta accreta in subsequent pregnancy: a case-control study.

OBJECTIVE: To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC). DESIGN: Case-control study. SETTING: Eleven tertiary referral hospitals in central Japan. POPULATION: A total of 98 cases of placenta praevia, a history of one or more prior caesarean sections, and a history of uterine transverse incision and usage of only absorbable thread for myometrial sutures at the prior caesarean section. Exclusions were a history of myomectomy or Strassmann's operation. METHODS: Cases were grouped into a pathologically diagnosed placenta accreta group (38 cases) and a no accreta group (60 cases). Clinical characteristics including uterine suture methods at prior caesarean section were compared (single-layer versus double-layer closure; continuous versus interrupted sutures in the inner myometrial layer). MAIN OUTCOME MEASURE: The incidence of placenta accreta. RESULTS: No difference was found comparing single-layer with double-layer closure in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a significant difference was found comparing continuous with interrupted sutures (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with stepwise selection for the eight factors meeting the criterion of P < 0.10 in univariate analysis was used, and four independent factors were selected, as follows: gravidity ≥ 3 (adjusted odds ratio, aOR, 3.4, 95% confidence interval, 95% CI, 0.99-11.6, P = 0.050); total praevia (versus non-total, aOR 18.4, 95% CI 3.2-107.0, P = 0.001); anterior/centre placenta (versus posterior, aOR 16.4, 95% CI 3.7-72.2, P < 0.001); and continuous sutures (versus interrupted, aOR 6.0, 95% CI 1.4-25.2, P = 0.015). CONCLUSIONS: In this limited study, a history of continuous sutures on the inner side of the uterine wall showed potential to influence the development of placenta accreta in PPPC patients.

Results of the Health Assessment Questionnaire for Japanese patients with systemic sclerosis--measuring functional impairment in systemic sclerosis versus other connective tissue diseases.

OBJECTIVE: To evaluate the physical functional impairment in patients with systemic sclerosis (SSc) using the Health Assessment Questionnaire (HAQ) and to estimate the correlation of HAQ scores with the severity of SSc. METHODS: One hundred and twenty-four outpatients with connective tissue disease, including 50 patients with SSc, were evaluated using the HAQ. Twelve patients were classified as having diffuse cutaneous SSc (dSSc) and 38 limited cutaneous SSc (lSSc). The severity classification and the guidelines for treatment (2004) were applied to Japanese SSc patients in order to evaluate the relationship between HAQ scores and disease activity in patients with multiple organ involvement. RESULTS: In dSSc the HAQ category scores for eating, walking, grip, activity and the HAQ-disability index (HAQ-DI) showed the greatest deficits in all disease groups. The severity of disease activity correlated significantly with the scores for walking, reach, and the HAQ-DI. The severity of joint, heart, and pulmonary hypertension were correlated independently with the HAQ-DI score by multiple linear regression analysis. CONCLUSION: Patients with dSSc suffer greater functional impairment than patients with other connective tissue diseases, and improvements in hand use and walking represent very important targets for both drug development and rehabilitation. As improvement in organ involvement (joints, heart as well as pulmonary hypertension) can lead to reduced functional impairment, they constitute an important target for therapy in SSc.

Long-term weight-change slope, weight fluctuation and risk of type 2 diabetes mellitus in middle-aged Japanese men and women: findings of Aichi Workers' Cohort Study.

OBJECTIVE: This study aims to investigate the association of long-term weight-change slopes, weight fluctuation and the risk of type 2 diabetes mellitus (T2DM) in middle-aged Japanese men and women. METHODS: A total of 4234 participants of Aichi Workers' Cohort Study who were aged 35-66 years and free of diabetes in 2002 were followed through 2014. Past body weights at the ages of 20, 25, 30, 40 years, and 5 years before baseline as well as measured body weight at baseline were regressed on the ages. Slope and root-mean-square-error of the regression line were obtained and used to represent the weight changes and the weight fluctuation, respectively. The associations of the weight-change slopes and the weight fluctuation with incident T2DM were estimated by Cox proportional hazards models. RESULTS: During the median follow-up of 12.2 years, 400 incident cases of T2DM were documented. After adjustment for baseline overweight and other lifestyle covariates, the weight-change slopes were significantly associated with higher incidence of T2DM (hazard ratio (HR): 1.80, 95% confident interval (CI): 1.17-2.77 for men; and HR: 2.78, 95% CI: 1.07-7.23 for women), while the weight fluctuation was not (HR: 1.08, 95% CI: 1.00-1.18 for men and HR: 1.02, 95% CI: 0.84-1.25 for women). CONCLUSIONS: Regardless of the presence of overweight, the long-term weight-change slopes were significantly associated with the increased risk of T2DM; however, the weight fluctuation was not associated with the risk of T2DM in middle-aged Japanese men and women.

The relationship between three signs of fetal magnetic resonance imaging and severity of congenital diaphragmatic hernia.

OBJECTIVE: To seek a simple approach for prenatally classifying congenital diaphragmatic hernia (CDH) severity using fetal magnetic resonance imaging (MRI) markers. STUDY DESIGN: A retrospective, multicenter study using questionnaires to investigate fetal MRI findings. We included fetuses prenatally diagnosed with isolated left-sided CDH and delivered after 36 weeks of gestation. We focused on three fetal MRI morphological signs: incomplete pulmonary baseline (IPB), liver up (LU) and retrocardiac stomach (RCS). We also evaluated the fetal MRI score defined as the total number of positive signs; the primary outcome was survival at discharge. RESULTS: In 256 patients (from 56 institutions), IPB, LU and RCS findings correlated with lower survival: odds ratio (95% confidence interval), 0.16 (0.08 to 0.33); 0.24 (0.12 to 0.51); and 0.14 (0.07 to 0.28); respectively. Patients with higher fetal MRI scores had a higher mortality rate. CONCLUSION: IPB, LU and RCS on fetal MRI are related to CDH severity.

New murine model for hepatocellular carcinoma: transgenic mice expressing metallothionein-ovine growth hormone fusion gene.

Hepatocellular carcinomas developed at a high frequency in the livers of transgenic (C57BL/6 X SJL/J)F1 mice under the influence of growth hormone. Three lines of giant transgenic mice expressing a mouse metallothionein-ovine growth hormone fusion gene were generated. The giant mice weighed twice as much as control littermates. The three lines of giant mice expressing very high levels of growth hormone were bred over several generations. Mice from all three lines developed hepatocellular tumors, including adenoma and carcinoma. The occurrence of tumors was age-dependent, and their incidence increased to 70% of the mice studied after 43 weeks of age. Pathologic changes in the livers resembled those observed in rats in which hepatocellular carcinomas are induced chemically. Transgenic mice carrying the metallothionein-ovine growth hormone fusion gene represent a new model for hepatocellular carcinogenesis. This model exemplifies the oncogenic potential for a sustained proliferative growth stimulus within an organ.

Monoclonal antibodies against an alpha-amylase inhibitor from wheat kernel.

An alpha-amylase inhibitor (called the 0.53-inhibitor, Maeda, K., Takamori, Y. and Oka, O. (1982) Agric. Biol. Chem. 41, 2873-2875) and the carboxymethylated inhibitor were used to immunize mice (strain BALB/c) according to a procedure described earlier (McMaster, W.R. and Williams, A.F., (1979) Eur. J. Immunol. 9, 426-433). After fusion of spleen cells with NS-1 myeloma cells, three stable clones producing antibodies against the inhibitor were obtained. The binding characteristics of the monoclonal antibodies, AWAI-1, AWAI-2 and AWAI-3, to the inhibitor were analyzed by radioimmunoassay. Two of these monoclonal antibodies to the alpha-amylase inhibitor did not show any binding affinity towards carboxymethylated inhibitor, suggesting that the main antigenic determinant on the native inhibitor is tertiary-structure dependent. The monoclonal antibodies obtained cross-reacted with three other alpha-amylase inhibitors (the 0.19-, the 0.36- and the 0.38-inhibitor) in wheat and these were separated together with the 0.53-inhibitor from the rest of inhibitors by immunoaffinity chromatography. One stable clone producing antibody against the carboxymethylated inhibitor was also established, AWAI-4. The antigenic determinant to this antibody was found to be included in the region of Met(5)-Lys(25) on the carboxymethylated inhibitor.

Familial aggregation and coaggregation of history of hypertension and stroke.

We attempted to evaluate familial aggregation and coaggregation of history of hypertension and stroke. Past and family history of hypertension and stroke for 83 089 probands and their relatives were obtained from a data set for the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Ministry of Education (JACC Study), which was initiated from 1988 to 1990. First, evaluation was performed for familial aggregation of each of two disorders using ordinal logistic regression of the generalized estimation equations (GEE) to account for dependence of observations within families. Secondly, in order to evaluate the familial congregation of the history of hypertension and stroke, a GEE-based multivariate probed predictive model was applied. After adjusting for the proband's age, level of obesity, smoking status, drinking status, habitation area, and the gender and type of the relatives, the estimated odds ratios for the intraindividual clustering and familial aggregation of the disease history showed statistically significant relationships. In addition, the history of the two disorders showed a significant relationship in terms of familial coaggregation independently of the aggregation of each disorder itself. Our results confirmed that hypertension and stroke coaggregate strongly within families through possible effects of genetic factors, which, alone or in conjunction with environmental factors, influence susceptibility to both hypertension and stroke.

Effects of 17 beta-estradiol and progesterone on migration of human monocytic THP-1 cells stimulated by minimally oxidized low-density lipoprotein in vitro.

OBJECTIVE: Many epidemiological studies have shown that postmenopausal hormone replacement therapy (HRT) has a beneficial effect on atherosclerotic cardiovascular disease. The aim of this study was to investigate the effects of estrogen and progestin on the migration of monocytes induced by minimally oxidized low-density lipoprotein (m-ox-LDL) in vitro. METHODS: Human monocytic THP-1 cells were used for the study. Migration assay was performed using a modified Boyden chamber. RESULTS: The presence of estrogen receptors was determined in THP-1 cells by Western and Northern blot analysis. Although native LDL had no significant effects on the migration of THP-1 cells, m-ox-LDL increased the migration of THP-1 cells in a dose-dependent manner. Although 17 beta-estradiol (E2, 10(-9)-10(-6) M) inhibited the 10 micrograms/ml-induced migration of THP-1 cells in a dose-dependent manner, estrone (E1), estriol (E3) and progesterone (P) had no significant effects. The combination of P (10(-9)-10(-6) M) did not show any effect on the inhibitory effect of 10(-7) M E2. Preincubation of THP-1 cells with the anti-estrogenic agent, tamoxifen (10(-6) M), significantly antagonized the inhibitory effect of 10(-7) M E2. m-ox-LDL stimulated MCP-1 secretion from THP-1 cells, which was reduced by E2. Anti-human MCP-1 neutralizing antibody inhibited the migration of THP-1 cells stimulated by m-ox-LDL. E2 also inhibited the 10 ng/ml MCP-1-induced migration of THP-1 cells in a dose-dependent manner. CONCLUSIONS: These findings suggest that the inhibitory effect of E2 on the migration of monocytes might be one of the factors involved in the decreased incidence of atherosclerotic cardiovascular disease in premenopausal women and postmenopausal HRT.

Increased matrix metalloproteinase-9 activity in human ovarian cancer cells cultured with conditioned medium from human peritoneal tissue.

Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4 mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M(r) 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers.

Sensitisation of human ovarian carcinoma cells to cis-diamminedichloroplatinum (II) by amphotericin B in vitro and in vivo.

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedichloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 microM, respectively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We prepared HRA cell-inoculated nude mice as an experimental therapeutic model for human advanced ovarian carcinoma. Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mice died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/kg) alone 4 days after inoculation increased MST by only 1.4 days. Simultaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2.0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that platinum accumulation in tumour tissues in nude mice treated with CDDP and AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy with CDDP and AMB is effective in an experimental animal model of advanced ovarian carcinoma.

Positive correlation between inhibitors of matrix metalloproteinase 1 and matrix metalloproteinases in malignant ovarian tumor tissues.

To investigate the relation between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in malignant ovarian tumor, MMP and TIMP activities in conditioned media of 16 malignant ovarian tumor tissues and six normal ovaries were detected by zymography and reverse zymography, respectively and were quantitated with a densitometer. TIMP-1 and TIMP-2 were detected in all normal and malignant ovarian tumor tissues by reverse zymography. In normal ovaries, the intensity of TIMP-2 bands was stronger than TIMP-1, but in malignant tumor tissues those of TIMP-1 were stronger. The ratios of TIMP-1 to TIMP-2 and MMP-9 to MMP-2 were significantly higher in malignant tumor tissues than in normal ovaries (P < 0.001). TIMP activity consisting of TIMP-1 and TIMP-2 correlated significantly to MMP activity of MMP-2 and MMP-9 (r = 0.67, P < 0.005). There was a significant correlation between TIMP-1 activity and MMP activity (r = 0.72, P < 0.001), but no correlation was observed between TIMP-2 activity and MMP activity. The high level of TIMP-1 appeared to be related to malignant phenotype in ovaries as well as the high level of MMP-9.

Squamous cell carcinoma arising from mature cystic teratoma of the ovary: a clinicopathologic analysis.

OBJECTIVE: There have been few studies concerning the clinical pathology of squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the objective of this study is to determine clinicopathologic factors affecting survival in this rare tumor. METHODS: From September 1979 to June 1996, 37 patients with squamous cell carcinoma arising from ovarian mature cystic teratoma were treated by the Tokai Ovarian Tumor Study Group. A retrospective clinicopathologic and survival analysis of these patients was performed. The mode of infiltration was classified into expansive, moderately diffused, and diffused patterns. RESULTS: Although the 5-year survival rate was 94.7% and 80.0% for stage I and II patients, respectively, 12 of 13 patients with stage III died within 20 months (P = .0001). A significant difference was also observed between the survival of the groups with and without residual tumor at surgery (P = .0001). Pathologic features, grade, mode of infiltration, and vascular involvement were significant factors by univariate analysis. Multivariate analysis showed significant differences in survival related to grade (P = .0154) and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma antigen level was significantly higher in the patients with squamous cell carcinoma arising from mature cystic teratoma than in patients with mature cystic teratoma (P < .0001). CONCLUSION: This study suggests that pathologic factors, grade, and mode of infiltration can provide valuable information for predicting the survival of patients with squamous cell carcinoma arising from mature cystic teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to detect this disease preoperatively.

Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma.

High levels of IL-6 have been observed in ascitic fluid in patients with ovarian cancer. In this study, we examined the effects of IL-6 on in vitro invasiveness of human ovarian cancer cells. Human ovarian cancer cells, NOM1 and SKOV, were used. Cell attachment to Matrigel, migration, and invasion were examined with or without IL-6. Zymography was performed to analyze gelatinase production by these cells. NOM1 cell attachment was increased by IL-6 (0 to 10 ng/ml). In a migration assay, IL-6 ranging from 0 to 10 ng/ml showed chemotactic and/or chemokinetic activities for the two cell lines. The invasiveness of these cells was significantly enhanced by IL-6 at the above concentrations. However, IL-6 did not modulate the production of either MMPs or TIMPs. IL-6 affects cell invasion through its effects on attachment and migration in human ovarian cancer cells. IL-6 might thus contribute to the progression of this disease.

Distribution of platinum in human gynecologic tissues and lymph nodes after intravenous and intraarterial neoadjuvant chemotherapy.

Fourteen patients with ovarian and cervical cancer were treated with platinum drug-based intravenous and intraarterial neoadjuvant chemotherapy, respectively, followed by reductive surgery. Platinum accumulation in tissues was assayed to compare the distribution of platinum in cancer tissues, myometrium, ovary, and pelvic lymph node following intravenous and intraarterial administration. Platinum accumulation was higher in the cancer tissue and in the myometrium than in the ovary and the lymph nodes after the intraarterial neoadjuvant chemotherapy. The level of platinum accumulation in tissues to that in the cancer tissues was calculated and compared between the two groups. The level of platinum accumulation in the lymph node to that in the cancer tissue was significantly higher in the intravenous than in the intraarterial group. Furthermore, the relative platinum accumulation was calculated from the total dosage of cisplatin administered. The relative platinum accumulation in the cancer tissue and the myometrium was significantly higher in the intraarterial than in the intravenous group. However, there were no significant differences in the lymph nodes. These findings suggest that intraarterial neoadjuvant chemotherapy should be effective on advanced cervical cancer.

The different stimulatory effect of normal tissues on the secretion of matrix metalloproteinases and their inhibitors by human ovarian cancer cells.

To investigate the influence of normal tissues on secretion of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by ovarian cancer cells, conditioned medium of several normal human tissues (peritoneum, myometrium, and ovary) was added to ovarian cancer cells (NOM1). MMPs were detected by zymography and TIMP-1 levels were assayed by ELISA. The MMP-9 level was significantly higher in peritoneal conditioned medium than in myometrial and ovarian conditioned medium, but the TIMP-1 level was the lowest. Addition of conditioned medium from these normal tissues to NOM1 cells increased the levels of MMPs and TIMP-1 in NOM1 conditioned medium. Peritoneal conditioned medium induced the highest MMP-9 level in NOM1 conditioned medium, while TIMP-1 was the lowest. Conditioned medium from the normal tissues also significantly increased invading cell numbers, with peritoneal conditioned medium being the most potent. These results showed that secretion of MMPs and TIMP-1 is regulated by normal tissues and peritoneum provides the best conditions for ovarian cancer cell invasion.

Potentiating effect of amphotericin B on five platinum anticancer drugs in human cis-diamminedichloroplatinum (II) sensitive and resistant ovarian carcinoma cells.

We have determined an effect of amphotericin B (AMB), an antifungal drug, on the cytotoxicity of cis-diamminedichloro-platinum (II) (CDDP) and 4 CDDP analogues in a human ovarian carcinoma cell line (NOS2). Intracellular accumulation of CDDP was elevated significantly by treatment with AMB, and AMB significantly potentiated the cytotoxicity of CDDP by MTT assay. Intracellular accumulation of 4 CDDP analogues was also elevated by the treatment with AMB and the order of increasing accumulation rate of platinum drugs was consistent with that of dose modification factor (DMF). AMB also increased the intracellular CDDP accumulation in CDDP resistant cells (NOS2CR), derived from NOS2. The intracellular accumulations of 4 CDDP analogues were elevated slightly by the treatment with AMB in NOS2CR cells. DMFs of 5 platinum drugs in NOS2CR cells, however, were more than those in NOS2 cells. These results indicate that AMB sensitizes NOS2 and NOS2CR cells to platinum drugs, partially due to the increasing intracellular accumulation of these drugs. In addition, CDDP analogues are more effective in NOS2CR cells than CDDP, but the cytotoxicity of CDDP was most potentiated by AMB among the 5 platinum drugs under study.

A newly synthesized bifunctional inhibitor, CKA1083, enhances adriamycin activity against human ovarian carcinoma cells.

BACKGROUND: A newly synthesized drug, CKA1083 ((S)-N-[2-(4-benzyloxy-carbonylpiperazinyl)-1-(P-methoxybenzyl) ethyl]-N-methyl-N(5-isoquinolinesulfonamide)), has the same glutathione-S-transferase (GST)-binding site structure as W-77, a bifunctional inhibitor that enhances the cytotoxicity of Adriamycin for human ovarian carcinoma cells. We examined the effects of CKA1083 on the cytotoxicity of Adriamycin and the resistance of human ovarian carcinoma cells to this drug. MATERIALS AND METHODS: We used GST-pi transfected cells and Adriamycin-sensitive or -resistant cells of human ovarian carcinoma. GST-pi activity, the intracellular Adriamycin content, and the cytotoxicity of Adriamycin in these cell lines in the presence or absence of CKA1083 were measured and compared to the findings obtained with W-77 or verapamil. RESULTS: CKA1083 inhibited GST-pi activity in an uncompetitive manner and more strongly than W-77. It enhanced the cytotoxicity of Adriamycin for GST-pi transfected cells by about 3-times. Further, CKA1083 increased the intracellular Adriamycin content about 3-fold in two Adriamycin-resistant cell lines (NOS2AR and NOS3AR). CKA1083 (10 microM) reduced the IC50 of Adriamycin to 1/38 in NOS2AR cells and 1/21 in NOS3AR cells, and overcame Adriamycin resistance more effectively than both W-77 and verapamil. CONCLUSIONS: CKA1083 enhanced the antitumor effect of Adriamycin more than W-77 by inhibiting both GST activity and P-glycoprotein.

Lymphadenectomy in stage-III serous cystadenocarcinoma of the ovary.

OBJECTIVE: To elucidate the effects of lymphadenectomy on the prognosis for ovarian cancer. METHOD: A retrospective study of 69 patients with stage-III serous cystadenocarcinoma was performed. RESULTS: Among the 69 patients, 36 were not treated by lymphadenectomy. Both pelvic and para-aortic lymphadenectomies were performed on 13 patients at the initial operation and on 11 at the second operation. The group (n = 13) treated by both pelvic and para-aortic lymphadenectomies at the initial operation had a disease-free survival rate that was significantly higher than the non-lymphadenectomy group (n = 36) or the group (n = 5) treated by pelvic or para-aortic lymphadenectomy alone (P < 0.04). These 54 patients were subjected to multivariate analysis for lymphadenectomy at the initial operation, and a significant correlation was found between disease-free survival rate and both pelvic and para-aortic lymphadenectomies (P < 0.05). CONCLUSION: These results suggest that systematic lymphadenectomy can reduce the rate of recurrence.

[Epidemiology and primary prevention of colorectal cancer].

The incidence of and mortality from colorectal cancer are increasing in Japan, as is its proportion among all malignant neoplasms. Thus, primary prevention of this cancer is crucial. Colorectal cancer is caused by interactions between host and environmental factors, with accumulation of gene alterations, such as activation of oncogenes and inactivation of suppressor genes, and generally involves an adenoma-carcinoma sequence. Carcinogenesis progresses with multi-factor, multi-hit and multi-stage mechanisms. According to the report by WCRF/AICR, convincing preventive factors include eating vegetables (not fruit) and physical activity (colon only), while probable risk factors are red meat and alcohol. Possible preventive factors include dietary fiber, starch and carotenoids, whereas possible risk factors include high body mass, fat and heavily cooked meat. Such preventive and risk factors for colorectal cancer are discussed in this review.

Association of coffee consumption with serum adiponectin, leptin, inflammation and metabolic markers in Japanese workers: a cross-sectional study.

BACKGROUND: Mechanisms underlying coffee's beneficial actions against cardiovascular disease and glucose metabolism are not well understood. Little information is available regarding association between coffee consumption and adipocytokines. OBJECTIVE: We investigated potential associations between coffee consumption and adiponectin, leptin, markers for subclinical inflammation, glucose metabolism, lipids and liver enzymes. We then investigated whether adipocytokines played a role in the association between coffee consumption and these markers. DESIGN AND SUBJECTS: This is a cross-sectional study comprising 2554 male and 763 female Japanese workers. Potential relations between coffee consumption and adipocytokines or other markers were evaluated using a multiple linear regression model adjusted for confounding factors. We evaluated whether adiponectin and leptin partly explain the associations between coffee consumption and each marker by multiple mediation analysis. RESULTS: Coffee consumption showed significant positive associations with adiponectin and total and low-density lipoprotein cholesterol, and inverse associations with leptin, high sensitivity C-reactive protein (hs-CRP), triglycerides and liver enzymes (all P<0.05). An adjustment for adiponectin and leptin significantly attenuated the associations between coffee consumption and hs-CRP or triglycerides, but not for liver enzymes. No associations were observed between coffee consumption and glucose metabolism-related markers. CONCLUSION: Coffee consumption was associated with high adiponectin and low leptin levels. We speculated that adipocytokines mainly explain the associations of coffee consumption with lipids and hs-CRP. Factors other than adipocytokines may explain the association between coffee consumption and liver function.