Satoru Matsuyama

Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population

BACKGROUND One of the most critical questions in immunosurveillance is whether differences between individuals with regards to natural immunological host defence can predict future development of cancer. Although this question has so far remained open, there are clear indications of significant roles of several naturally cytotoxic lymphocytes in preventing the development of cancer. We began a prospective cohort study among a Japanese general population in 1986, using various immunological and biochemical markers. METHODS Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by isotope-release assay in 3625 residents of a Japanese population mostly older than 40 years of age, between 1986 and 1990. Immunological and biochemical markers were also measured, and participants were given a questionnaire on lifestyle. We did an 11-year follow-up survey of the cohort members looking at cancer incidence and death from all causes, and analysed the association between cytotoxic activity of peripheral-blood lymphocytes assessed at baseline and cancer incidence found in the subsequent follow-up. FINDINGS 154 cancer cases were used in the analysis. When we categorised the cytotoxic activity of peripheral-blood lymphocytes by tertiles, age-adjusted relative risk of cancer incidence (all sites) was 0.72 (95% CI 0.45-1.16) for men with high cytotoxic activity, and 0.62 (0.38-1.03) for men with medium cytotoxic activity, taking the risk of those with low cytotoxic activity as reference. For women with high cytotoxic activity relative risk was 0.52 (0.28-0.95), and for those with medium cytotoxic activity 0.56 (0.31-1.01). For both sexes with high and medium cytotoxic activity risk was 0.63 (0.43-0.92) and 0.59 (0.40-0.87), respectively. INTERPRETATION Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk, whereas low activity is associated with increased cancer risk suggesting a role for natural immunological host defence mechanisms against cancer.

Green tea and cancer chemoprevention.

Worldwide interest in green tea as a cancer preventive agent for humans has increased, because it is non-toxic and it is effective in a wide range of organs. (-)-Epigallocatechin gallate (EGCG) is the main constituent of green tea; the others are (-)-epicatechin gallate, (-)-epigallocatechin and (-)-epicatechin (EC). This paper reports the results of our latest pharmacological and biochemical studies with 3H-EGCG, along with studies on human subjects. The study on bioavailability of 3H-EGCG in mice revealed the wide distribution of radioactivity in multiple organs. Specifically, radioactivity was found in all reported target organs of EGCG and green tea extract (digestive tract, liver, lung, pancreas, mammary gland and skin) as well as other organs (brain, kidney, uterus and ovary or testes) in mice. Recently, we demonstrated that EC enhanced incorporation of 3H-EGCG into human lung cancer cell line PC-9 cells. EC along with another cancer preventive agent sulindac also synergistically enhanced apoptosis in PC-9 cells induced by EGCG. Moreover, a case-control study on breast cancer patients revealed that high daily consumption of green tea was associated with a lower recurrence rate among Stages I and II patients. All the results suggest that consumption of green tea is a practical and effective cancer preventive both before cancer onset and after cancer treatment.

A New Function of Green Tea: Prevention of Lifestyle‐related Diseases

Abstract: In the normal human life span, there occur lifestyle‐related diseases that may be preventable with nontoxic agents. This paper deals with the preventive activity of green tea in some lifestyle‐related diseases. Green tea is one of the most practical cancer preventives, as we have shown in various in vitro and in vivo experiments, along with epidemiological studies. Among various biological effects of green tea, we have focused on its inhibitory effect on TNF‐α gene expression mediated through inhibition of NF‐κB and AP‐1 activation. Based on our recent results with TNF‐α‐deficient mice, TNF‐α is an endogenous tumor promoter. TNF‐α is also known to be a central mediator in chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. We therefore hypothesized that green tea might be a preventive agent for chronic inflammatory diseases. To test this hypothesis, TNF‐α transgenic mice, which overexpress TNF‐α only in the lungs, were examined. The TNF‐α transgenic mouse is an animal model of human idiopathic pulmonary fibrosis which also frequently develops lung cancer. Expressions of TNF‐α and IL‐6 were inhibited in the lungs of these mice after treatment with green tea in drinking water for 4 months. In addition, judging from the results of a prospective cohort study in Saitama Prefecture, Japan, green tea helps to prevent cardiovascular disease. In this study, a decreased relative risk of death from cardiovascular disease was found for people consuming over 10 cups of green tea a day, and green tea also had life‐prolonging effects on cumulative survival. These data suggest that green tea has preventive effects on both chronic inflammatory diseases and lifestyle‐related diseases (including cardiovascular disease and cancer), resulting in prolongation of life span.

Estrogen receptor β is expressed in human stomach adenocarcinoma

AbstractPurpose. In stomach adenocarcinoma, the role of the hormonal receptor, estrogen receptor (ER), has been controversial. Recently, a new estrogen receptor, called estrogen receptor β (ERβ), was found to be expressed in various tissues including normal gastrointestinal tract. In this paper, the expression of ERβ in stomach adenocarcinomas has been investigated for the first time, specifically in signet ring cell adenocarcinomas, together with surrounding non-cancerous tissues. Methods. By immunohistochemistry the expression of ERα and β was studied in 29 stomach adenocarcinomas, ten signet ring cell adenocarcinomas, and 19 other adenocarcinomas. Western blotting was performed to examine the immunohistochemical result. Statistical studies (Students t test and χ2-test) explored the relation between the immunohistochemical result and clinicopathological characteristics. Results. All 29 adenocarcinomas, including the signet ring cell ones, demonstrated clear ERβ nucleus staining. Lymphocytes, venous endothelial cells, smooth muscle, and non-cancerous stomach glands also showed strong ERβ staining, while no staining was observed in the immunohistochemistry of ERα. Western blotting showed equivalent ERβ protein levels in cancerous and non-cancerous tissues, which was consistent with the results of immunohistochemical staining. Among signet ring cell adenocarcinomas of the stomach, cytoplasm were stained in addition to nuclei, specifically in patients under the age of 40 years. Conclusions. Our results imply that the effects of estrogen in stomach cancer, as well as those in normal stomach, may be mediated by ERβ, and that the role of ERβ may differ by the subtype of stomach adenocarcinoma – specifically signet ring cell adenocarcinomas and other ones – although large scale samples are needed to confirm these findings.

Cancer prevention with green tea and monitoring by a new biomarker, hnRNP B1

The study of green tea polyphenols as a cancer preventative is approaching a new era, with significant results accumulating rapidly. This paper briefly reviews four topics related to mechanisms of action of tea polyphenols: (I) identification of the genes commonly affected by EGCG, as demonstrated by Clontechs Atlas cDNA Expression Array; (II) the significance of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1) as a new biomarker for early detection of lung cancer, and inhibition of its expression by EGCG; (III) the synergistic or additive effects of EGCG with the cancer preventive agents, sulindac and tamoxifen, on induction of apoptosis in PC-9 cells and on inhibition of intestinal tumor development in multiple intestinal neoplasia (Min) mice; (IV) the results of a 10 year prospective cohort study demonstrating the effectiveness of daily consumption of green tea in preventing cancer, and a prototype study for developing green tea beverage as cancer preventive.

Heterogeneous Nuclear Ribonucleoprotein B1 Expressed in Esophageal Squamous Cell Carcinomas as a New Biomarker for Diagnosis

We recently reported that heterogeneous nuclear ribonucleoprotein (hnRNP) B1 was overexpressed in most human lung cancers, especially squamous cell carcinoma (SCC), as well as human oral SCC. To find the significance of hnRNP B1 in cancer diagnosis, we studied hnRNP B1 expression in 16 paraffinized sections of esophageal SCC, using immunohistochemical staining with antihnRNP B1 polyclonal antibody, raised in a rabbit. We compared the expression of hnRNP B1 in cancerous and noncancerous regions of the same specimen: enhanced expression was observed in 63% of cancerous regions (10/16), whereas none of the noncancerous regions showed enhanced expression. The enhanced expression of hnRNP B1 in cancerous regions was compared with that in noncancerous tissue in relation to histopathological grade: 83% for well differentiated (5/6), 83% for moderately differentiated (5/6) and 0% for poorly differentiated (0/4). Histologically, enhanced expression of hnRNP B1 was observed around cancer pearls, as well as in the cells of nests lacking keratinization in well and moderately differentiated SCC. Western blotting analysis revealed enhanced expression in three frozen specimens of moderately differentiated SCC. Using esophageal cancer cell lines, we further confirmed the decreased expression in poorly differentiated SCC cells, compared with other differentiation types. All our results support the significance of hnRNP B1 expression in esophageal SCC as a unique diagnostic marker with regard to association between expression level and histopathological grading.

An unusual presentation of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing pyogenic liver abscess: Report of a case

We describe a rare case of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing pyogenic liver abscess in a 59-year-old man. The patient was diagnosed as having a hollow viscus perforation based on a sudden onset of acute abdominal pain along with radiological evidence of bilateral subphrenic feee air (pneumoperitoneum), and underwent an emergency laparotomy. Contrary to expectations, the surgery revealed no perforations of the hollow viscus, but instead a ruptured liver abscess at the dome of the right hepatic lobe was identified associated with suppurative peritonitis. To the best of our knowledge, such a case of spontaneous pneumoperitoneum secondary to the rupture of a gas-containing liver abscess is extremely rare.

Iliac lymph node metastasis of an unknown primary tumor: report of a case.

Metastasis to the lymph nodes around the iliac vessels from cancer of an unknown primary (CUP) tumor has not yet been reported in either the English or Japanese literature and it is therefore described herein for the first time. The patient was a 70-year-old woman with persistent right leg edema. Computed tomography (CT) displayed a mass around the iliac vessels while physical, laboratory, and other imaging examination did not show any other tumor. Preoperatively diagnosed as a retroperitoneal tumor, the patient underwent a tumor resection, but a histopathological examination revealed the tumor to be poorly differentiated squamous cell carcinoma. Only residual lymph nodes in the pelvis were detected by postoperative fluorine-18 fluorodeoxyglucose-positron emission tomography. Neither a primary lesion nor any signs of recurrence were demonstrated for 13 months after radiotherapy for the residual nodes. We herein discuss the diagnosis, treatment, and follow-up of this less common CUP.

A case of hepatocolic fistula after percutaneous drainage for a gas-containing pyogenic liver abscess.

We describe a rare of gas-containing pyogenic liver abscess which penetrated the adjacent colon, forming a hepatocolic fistula, after percutaneous transhepatic abscess drainage (PTAD) had been performed. To the best of our knowledge, this is the first report of hepatocolic fistula associated with a gasforming liver abscess in a diabetic patient, with radiological and surgical confirmation of the fistula.

1.2 – Green Tea as a Cancer Preventive

1 Abstract Green tea is now an acknowledged cancer preventive in Japan and will possibly soon be recognized as such in other countries. Initially, we found that (—)- epigallocatechin gallate (EGCG), the main constituent of green tea inhibited tumor promotion on mouse skin in a two-stage carcinogenesis experiment. Numerous additional studies revealed the anticarcinogenic effects of EGCG and green tea on various organs in rodent experiments. This paper reviews the unique role of green tea in cancer chemoprevention, its anticarcinogenic effects and other preventive activities, bioavailability of tea polyphenols and epidemiological studies with green tea. Of particular interest are studies which showed that daily consumption of green tea delayed clinical onset of various cancers and led to more hopeful prognoses for breast cancer patients in Stage I and II following treatment. Based on these results, I propose two stages of cancer prevention with green tea: prevention before cancer onset, and following cancer treatment. Since green tea is a common beverage, the knowledge that it inhibits cancer will be a great comfort to, especially, aging folk concerned with cancer prevention and any high risk population.