Green tea is a daily beverage, a non-oxidized non-fermented product containing at least four green tea catechins. Considering our first results when repeated applications of (-)-epigallocatechin gallate (EGCG) prevented tumor promotion in mouse skin, we have continued to look at green tea as a possible cancer preventive agent. 1) The 10-year prospective cohort study by Drs. K. Nakachi and K. Imai revealed that drinking 10 Japanese-size cups (120 mL/cup) of green tea per day delayed cancer onset in humans by 7.3 years among females and by 3.2 years among males. The delay of cancer onset is of course significant evidence of primary cancer prevention in humans. 2) In collaboration with Dr. H. Moriwaki's group we successfully presented a prototype of tertiary cancer prevention showing that 10 Japanese-size cups of green tea daily, supplemented with tablets of green tea extract (G.T.E), reduced recurrence of colorectal adenomas in polypectomy patients by 51.6% (from 31% to 15%). 3) In 1999, we first reported that the combination of green tea catechins and non-steroidal anti-inflammatory drugs showed synergistic anticancer effects in both in vitro and in vivo experiments, along with elucidation of the mechanism. 4) Further studies by other investigators have revealed that various combinations of EGCG or green tea extract and anticancer compounds inhibit tumor volume in xenograft mouse models implanted with various human cancer cell lines. Green tea is a cancer preventive, and green tea catechins act as synergists with anticancer compounds.
Adenoma ; Animals ; Beverages ; Catechin* ; Cell Line ; Cohort Studies ; Cooperative Behavior ; Drinking ; Female ; Heterografts ; Humans ; Male ; Mice ; Prospective Studies ; Recurrence ; Research Personnel ; Skin ; Tablets ; Tea* ; Tumor Burden

STUDY DESIGN: A retrospective study. PURPOSE: The aims of this study were to investigate the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PET/computed tomography (CT) in the evaluation of spinal metastatic lesions. OVERVIEW OF LITERATURE: Recent studies described limitations regarding how many lesions with abnormal 18F-FDG PET findings in the bone show corresponding morphologic abnormalities. METHODS: The subjects for this retrospective study were 227 patients with primary malignant tumors, who were suspected of having spinal metastases. They underwent combined whole-body 18F-FDG PET/CT scanning for evaluation of known neoplasms in the whole spine. 99mTc-methylene diphosphonate bone scan was performed within 2 weeks following PET/CT examinations. The final diagnosis of spinal metastasis was established by histopathological examination regarding bone biopsy or magnetic resonance imaging (MRI) findings, and follow-up MRI, CT and 18F-FDG PET for extensively wide lesions with subsequent progression. RESULTS: From a total of 504 spinal lesions in 227 patients, 224 lesions showed discordant image findings. For 122 metastatic lesions with confirmed diagnosis, the sensitivity/specificity of bone scan and FDG PET were 84%/21% and 89%/76%, respectively. In 102 true-positive metastatic lesions, the bone scan depicted predominantly osteosclerotic changes in 36% and osteolytic changes in 19%. In 109 true-positive lesions of FDG PET, osteolytic changes were depicted predominantly in 38% while osteosclerotic changes were portrayed in 15%. CONCLUSIONS: 18F-FDG PET in PET/CT could be used as a substitute for bone scan in the evaluation of spinal metastasis, especially for patients with spinal osteolytic lesions on CT.
Biopsy ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Retrospective Studies ; Spine ; Technetium Tc 99m Medronate

To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2(/TIS21)), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach. Expression was increased in the mucous epithelium following H. pylori infection in contrast to its loss in human gastric adenocarcinoma. Indeed, adenoviral transduction of BTG2(/TIS21) significantly inhibited Tipα activity in MKN-1 and MGT-40, human and mouse gastric cancer cells, respectively, thereby downregulating tumor necrosis factor-α (TNFα) expression and Erk1/2 phosphorylation by reducing expression of nucleolin, a Tipα receptor. Chromatin immunoprecipitation proved that BTG2(/TIS21) inhibited Sp1 expression and its binding to the promoter of the nucleolin gene. In addition, BTG2(/TIS21) expression significantly reduced membrane-localized nucleolin expression in cancer cells, and the loss of BTG2(/TIS21) expression induced cytoplasmic nucleolin availability in gastric cancer tissues, as evidenced by immunoblotting and immunohistochemistry. Higher expression of BTG2 and lower expression of nucleolin were accompanied with better overall survival of poorly differentiated gastric cancer patients. This is the first report showing that BTG2(/TIS21) inhibits nucleolin expression via Sp1 binding, which might be associated with the inhibition of H. pylori-induced carcinogenesis. We suggest that BTG2(/TIS21) is a potential inhibitor of nucleolin in the cytoplasm, leading to inhibition of carcinogenesis after H. pylori infection.

Background/Aims: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD). Methods: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. Results: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. Conclusions In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)