7. CANCER PC- ECE anti-tumor effects currently tested only for dermatologic cancers in mice. No clinical studies of the anti-cancer potential of PC- ECE have been conducted to date, although a single murine dermatological cancer study performed on PC- ECE is summarized below: Chemoprevention of UVB-induced Skin Carcinogenesis by PC- ECE on SKH-1 Mice 1. Purpose of the Study: Chronic exposure of solar ultraviolet B (UVB) radiation to skin induces oxidative stress, which plays a crucial role in the induction of non-melanoma skin cancer. In this study, the research investigated the effect of oral feeding and topical application of PC- ECE on UVB radiation-induced skin carcinogenesis on SKH-1 mice. 2. Protocol: SKH-1 hairless mice (N=48) were treated orally or topically with PC- ECE and irradiated with UVB three times (160mJ/cm2) per week for 26 weeks. 3. Summary of Results - In both dietary and topical treatment of PC- ECE ? Significantly reduced tumor multiplicity by ~50% ? Significantly decreased PGE2 levels by 50~80% ? Significant down-regulation of inflammatory genes (COX2 and iNOS) was also observed through RT-PCR, Western Blot, etc ? Regulation of other genes are in question 32 - 32 -32 COX-2/iNOS activity COX-2/iNOS Gene Expression! Chemoprevention and Support Program, Division of Hematology and Oncology, Dept. of Internal Medicine, College of Medicine and Public Health, Ohio State University The results of this study provide evidence that PC- ECE possesses excellent anti-photo carcinogenesis effect, which may be associated with the prevention of UVB-mediated oxidative stress, an inflammation pathway in the skin.The study also indicates potential for chemoprevention of other types of cancer.8 Another outcome of the study was the finding that PC- ECE affords strong protection against UVB-induced iNOS suppression and inflammatory damage in the skin. Chronic exposure to UVB induced substantial increase in iNOS expression! together with severe damage in the skin. However PC- ECE significantly inhibited the production of iNOS by 48-78% depending upon dosage level and delivery method (dietary or topical). 9
8.ALLERGIES 8 H. Hwang, T. Chen, R. Nines, H-C Shin, G. Stoner. Photochemoprevention of UVB ? induced skin carcinogenesis in SKH-1 mice by brown algae polyphenols. International Journal of Cancer: 119, 2742-2749 (2006). 9 H. Hwang, T. Chen, G. Stoner, K-B Lee, Y-C Yoo, H-C Shin. Suppression of iNOS Expression! by Phlorotannins in Chronic Exposure of Skin to UVB Radiation. Laboratory Animal Research 2005; 21(4), 385-389. 33 - 33 -33 PC- ECE has been shown to dramatically relieve allergic reactions without any drowsiness, dizziness and other side effect of anti-histamine drugs. Its effectiveness has been demonstrated by allergen-induced murine asthma model by Dr. Chi, Dept. of Histopathology, University of Washington. Effect of PC- ECE on Allergen-induced murine asthma model Airway infiltration and remodeling in chronic asthma is characterized by eosinophils, mucus cell hyperplasia with mucus hypersecretion accumulation of mononuclear cells in airway interstitium and sub-epithelial fibrosis of the airway wall. PC- ECE (“KLS” in test results) was tested in a mouse model of allergen induced chronic lung inflammation and fibrosis. BALB/c mice, after I.P. OVA sensitization on day 0 and day 14, gave intranasal (i.n.) inhalation of OVA weekly about day 14-60. The OVA-treated and challenged mice developed an extensive eosinophil and mononuclear cell inflammatory response, mucus cell hyperplasia and mucus occlusion of the airway striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated control mice. PC- ECE was tested and found effective in reducing allergic reaction in inflammation. By feeding at a concentration of 5.4 mg/ml in the drinking water for 12 days, PC- ECE reduced the airway mucus plugging, and sub-epithelial fibrosis in the OVA-sensitized/ challenged mice. The reduced BAL fluid eosinophil indicated that PC- ECE is effective in improving the asthmatic lung structures. 12 days of feeding, PC- ECE demonstrated no pathological alterations in the liver, kidney, spleen, or small intestine. Summary of results: - Eosinophil migration in the lung reduced by 75% - Cellular infiltration (CD4+4 T Cells, resultant cytokines Il-4, 5, 13) reduced by 50% - Mucus plug in airways reduced by 75% - Airway epithelial hyperplasia reduced by 75% - Collagen in lung interstitium (fibrosis, airway remodeling) and smooth muscle cell thickness reduced by 20% and 32%, respectively
7. CANCER PC- ECE anti-tumor effects currently tested only for dermatologic cancers in mice. No clinical studies of the anti-cancer potential of PC- ECE have been conducted to date, although a single murine dermatological cancer study performed on PC- ECE is summarized below: Chemoprevention of UVB-induced Skin Carcinogenesis by PC- ECE on SKH-1 Mice 1. Purpose of the Study: Chronic exposure of solar ultraviolet B (UVB) radiation to skin induces oxidative stress, which plays a crucial role in the induction of non-melanoma skin cancer. In this study, the research investigated the effect of oral feeding and topical application of PC- ECE on UVB radiation-induced skin carcinogenesis on SKH-1 mice. 2. Protocol: SKH-1 hairless mice (N=48) were treated orally or topically with PC- ECE and irradiated with UVB three times (160mJ/cm2) per week for 26 weeks. 3. Summary of Results - In both dietary and topical treatment of PC- ECE ? Significantly reduced tumor multiplicity by ~50% ? Significantly decreased PGE2 levels by 50~80% ? Significant down-regulation of inflammatory genes (COX2 and iNOS) was also observed through RT-PCR, Western Blot, etc ? Regulation of other genes are in question 32 - 32 -32 COX-2/iNOS activity COX-2/iNOS Gene Expression! Chemoprevention and Support Program, Division of Hematology and Oncology, Dept. of Internal Medicine, College of Medicine and Public Health, Ohio State University The results of this study provide evidence that PC- ECE possesses excellent anti-photo carcinogenesis effect, which may be associated with the prevention of UVB-mediated oxidative stress, an inflammation pathway in the skin.The study also indicates potential for chemoprevention of other types of cancer.8 Another outcome of the study was the finding that PC- ECE affords strong protection against UVB-induced iNOS suppression and inflammatory damage in the skin. Chronic exposure to UVB induced substantial increase in iNOS expression! together with severe damage in the skin. However PC- ECE significantly inhibited the production of iNOS by 48-78% depending upon dosage level and delivery method (dietary or topical). 9
8.ALLERGIES 8 H. Hwang, T. Chen, R. Nines, H-C Shin, G. Stoner. Photochemoprevention of UVB ? induced skin carcinogenesis in SKH-1 mice by brown algae polyphenols. International Journal of Cancer: 119, 2742-2749 (2006). 9 H. Hwang, T. Chen, G. Stoner, K-B Lee, Y-C Yoo, H-C Shin. Suppression of iNOS Expression! by Phlorotannins in Chronic Exposure of Skin to UVB Radiation. Laboratory Animal Research 2005; 21(4), 385-389. 33 - 33 -33 PC- ECE has been shown to dramatically relieve allergic reactions without any drowsiness, dizziness and other side effect of anti-histamine drugs. Its effectiveness has been demonstrated by allergen-induced murine asthma model by Dr. Chi, Dept. of Histopathology, University of Washington. Effect of PC- ECE on Allergen-induced murine asthma model Airway infiltration and remodeling in chronic asthma is characterized by eosinophils, mucus cell hyperplasia with mucus hypersecretion accumulation of mononuclear cells in airway interstitium and sub-epithelial fibrosis of the airway wall. PC- ECE (“KLS” in test results) was tested in a mouse model of allergen induced chronic lung inflammation and fibrosis. BALB/c mice, after I.P. OVA sensitization on day 0 and day 14, gave intranasal (i.n.) inhalation of OVA weekly about day 14-60. The OVA-treated and challenged mice developed an extensive eosinophil and mononuclear cell inflammatory response, mucus cell hyperplasia and mucus occlusion of the airway striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated control mice. PC- ECE was tested and found effective in reducing allergic reaction in inflammation. By feeding at a concentration of 5.4 mg/ml in the drinking water for 12 days, PC- ECE reduced the airway mucus plugging, and sub-epithelial fibrosis in the OVA-sensitized/ challenged mice. The reduced BAL fluid eosinophil indicated that PC- ECE is effective in improving the asthmatic lung structures. 12 days of feeding, PC- ECE demonstrated no pathological alterations in the liver, kidney, spleen, or small intestine. Summary of results: - Eosinophil migration in the lung reduced by 75% - Cellular infiltration (CD4+4 T Cells, resultant cytokines Il-4, 5, 13) reduced by 50% - Mucus plug in airways reduced by 75% - Airway epithelial hyperplasia reduced by 75% - Collagen in lung interstitium (fibrosis, airway remodeling) and smooth muscle cell thickness reduced by 20% and 32%, respectively