Jie Du Tong Ye San Prevents N-Nitrosomethylbenzylamine-Induced Esophageal Carcinogenesis via Inhibition of Inflammation and Proliferation
Simin Zhao,1,2 Yanan Jiang,1,2 Tongde Tian,3 Jimin Zhao,1,2 Yifei Xie,1,2Xinhuan Chen,1,2 Jing Lu,1,2 Feng Yang,3 Honglin Li,2,4 Kangdong Liu,1,2and Ziming Dong1,2
Jie du tong ye san (JDTYS), a traditional Chinese herbal formula, has been used for cancer adjuvant therapy in clinical use and has been shown to be effective in cancer patients. However, the mechanism of JDTYS is still unclear. Therefore, the aim of the present study is to investigate the chemopreventive effects of JDTYS for esophageal squamous cell carcinoma (ESCC) and to clarify the potential mechanism. N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis was used to evaluate the effect of JDTYS in vivo. Rats were treated with NMBA 3 times per week, for a total of 5 weeks. Rats in the treated groups were given JDTYS for 35 weeks. When rats were euthanized, esophageal tissue and blood were collected to evaluate the effects of JDTYS. The pathological grading of the rat esophageal preneoplastic lesions was classified and statistically analyzed. The protein levels of c-Jun and Ki67 were determined by immunohistochemistry. In addition, inflammation markers nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and the cluster of differentiation molecule 11B (CD11B) were also determined by immunohistochemistry. Moreover, the expression of COX-2 and Pentraxin 3 (PTX3) in rat serum was determined by enzyme-linked immunosorbent assay (ELISA). JDTYS could inhibit the formation of NMBA-induced esophageal preneoplastic lesions. JDTYS could downregulate the expression of proliferation related proteins Ki67 and c-Jun. Moreover, inflammation related proteins NF-κB, COX-2, and CD11B were inhibited and PTX3 was increased by JDTYS. In all, JDTYS is a promising chemopreventive formula against esophageal carcinogenesis by regulating inflammation and inhibiting cell proliferation.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Green Tea Found to Reduce Rate of Some GI Cancers
Women who drink green tea may lower their risk of developing some digestive system cancers, especially cancers of the stomach/esophagus and colorectum, according to a study led by researchers from Vanderbilt-Ingram Cancer Center.
The study by lead author Sarah Nechuta, Ph.D., MPH, assistant professor of Medicine, was published online in advance of the Nov. 1 edition of the American Journal of Clinical Nutrition. Wei Zheng, M.D., Ph.D., MPH, professor of Medicine, chief of the Division of Epidemiology and director of the Vanderbilt Epidemiology Center, was the principal investigator for the study.
To determine green tea's impact on cancer risk, the investigators surveyed women enrolled in the Shanghai Women's Health Study, a population-based study of approximately 75,000 middle-aged and older Chinese women. During the initial interview participants were asked if they drank tea, the type of tea consumed and how much they consumed. Most of the Chinese women reported drinking primarily green tea.
The researchers found that regular tea consumption, defined as tea consumption at least three times a week for more than six months, was associated with a 17 percent reduced risk of all digestive cancers combined. A further reduction in risk was found to be associated with an increased level of tea drinking. Specifically, those who consumed about two to three cups per day (at least 150 grams of tea per month) had a 21 percent reduced risk of digestive system cancers.
The trend toward fewer digestive cancers was strongest for stomach/esophageal and colorectal cancers.
"For all digestive system cancers combined, the risk was reduced by 27 percent among women who had been drinking tea regularly for at least 20 years," said Nechuta. "For colorectal cancer, risk was reduced by 29 percent among the long-term tea drinkers. These results suggest long-term cumulative exposure may be particularly important."
Tea contains polyphenols or natural chemicals that include catechins like EGCG and ECG. Catechins have antioxidant properties and may inhibit cancer by reducing DNA damage and blocking tumor cell growth and invasion.
The researchers also asked about other lifestyle factors including the kinds of food eaten regularly, exercise habits, education level and occupation. Women who had ever smoked or who drank alcohol were excluded from the study.
Regular tea drinkers in the study were younger, had higher education, exercised more and consumed more fruits and vegetables. While the researchers adjusted for these factors, they could not rule out an effect from these and other unmeasured lifestyle habits.
The study was conducted in nonsmoking and nondrinking Chinese women to minimize the potential influence of these two risk factors on the results for tea consumption and digestive system cancer risk.
Source : Science Daily
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How an 1,800 year old Herbal Mix Heals the Gut
An ancient Chinese medicine might ease side effects of cancer treatments.
An age-old mixture of four herbs could spare patients with cancer some of the side effects of chemotherapy.The cocktail comprises Chinese peonies, Chinese liquorice, the fruit of the Chinese date tree and flowers of the Chinese skullcap plant. In China, they call it 'Huang Qin Tang' and have used it to treat gastrointestinal problems for about 1,800 years.
A start-up pharmaceutical company called PhytoCeutica has dubbed its proprietary pill of the blend 'PHY906', and shown in early clinical trials that the mix can combat the severe diarrhoea caused by many chemotherapy drugs, which destroy fast-dividing gut cells in addition to tumour cells.
Now, researchers at PhytoCeutica and Yale University School of Medicine, both in New Haven, Connecticut, have some early leads on how PHY906 does this, despite the fact that most of its individual chemical components remain unknown.
PHY906 still needs to prove itself in larger clinical trials. In 2004, the US Food and Drug Administration (FDA) eased regulations on herbal mixtures, allowing the approval of medicines that have been proved to be safe and effective, even if their individual components aren't known.
A green-tea extract produced by the German firm MediGene in Martinsried, and used against genital warts, was the first such medicine to be approved by the FDA under these rules.
"This is a new paradigm of drug development," says Yung-Chi Cheng, a pharmacologist at Yale and head scientific adviser to PhytoCeutica. "It's a typical example of West meets East."
Divide and Conquer
The latest results for PHY906, which provide molecular details indicative of how it might repair chemotherapy-damaged guts, could help PhytoCeutica to take its herbal drug down the same road. The results are published online today in Science Translational Medicine.
When mice receive a dose of the chemotherapy drug irinotecan, which blocks an enzyme, called topoisomerase, that is important to DNA replication, their gut cells begin to die off. However, a dose of PHY906 given with the chemotherapy restored these cells within four days, Cheng's team found. The guts of mice taking the herbal medicine contained fewer dying cells and more dividing cells than those of control animals.
The researchers measured the activity of genes in the gut cells of mice on PHY906 and irinotecan and found that genes in the Wnt pathway, which encourages progenitor cells in the gut to divide, were upregulated.
But ramping up the gut's stem cells isn't the only way that PHY906 combats diarrhoea, Cheng says. Irinotecan also causes inflammation, which the herbal medicine seems to prevent. The guts of mice on PHY906 contained fewer inflammatory immune cells called macrophages than did those of rodents on chemotherapy alone, and the activity of three genes linked to inflammation--Cox2, NF-�B and iNOS--was also down.
Cheng thinks that PHY906's multitude of effects can be explained through its different chemical constituents, and hopes that his team can identify which chemical is responsible for which change. "This will eventually simplify the procedures used for quality control," he says.
For now, Cheng and his colleagues at PhytoCeutica are using liquid chromatography, mass spectrometry and cell culture to try to establish a chemical and biological fingerprint for PHY906. This approach, he says, will ensure that each batch contains the same active ingredients.
"This group seems to have got quality control down to a fine art in terms of the components' activity," says chemical biologist Elaine Holmes of Imperial College London. But, she adds, "the worrying thing is that you're not controlling for toxicity."
Soil chemistry, humidity and even when during the day a plant is harvested affect its chemical make-up, Holmes notes. "I think we have to be cautious with the way we use traditional Chinese medicines and other herbal remedies."
Cheng's team will present phase I/II clinical trial results for PHY906 in patients with pancreatic cancer at a conference in Hong Kong next week. And Cheng hopes to get phase II and III trials going in the United States and Europe soon.
He adds that he would love to account for every last molecule in the medicine; it could even help his team to develop new drugs. However, at this stage, "the importance is for patients undergoing chemotherapy", he says.
Source : Scientific America