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Protective effects of baicalein against the initiation and promotion of carcinogenesis by ultraviolet B radiation in mice
P2308
P2310
PROTECTIVE EFFECTS OF BAICALEIN AGAINST THE INITIATION AND PROMOTION OF CARCINOGENESIS BY ULTRAVIOLET B RADIATION IN MICE Arash Akhavan, MD, Huachen Wei, MD, PhD, The Mount Sinai School of Medicine, New York, NY, United States Baicalein, a flavonoid isolated from the plant Scutellaria baicalensis, has been shown to have anticancer properties in cultured cell and animal models. We used two doses of baicalein in an animal model of Skh-1 hairless mice to investigate the inhibition of ultraviolet B (UVB)-generated tumor initiation and promotion. To study protection against UVB initiation of tumors, mice were first treated with either low-dose (5 nmol/L) or high-dose (20 nmol/L) baicalein, followed by a previously established tumor-initiating dose of UVB. Tumorigenesis was then promoted with a course of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Application of baicalein caused a dose-dependent decrease in UVB-induced tumor initiation. Application of low-dose baicalein reduced tumor incidence and multiplicity by 63.2% (P \ .05) and 79.7% (P \ .05), respectively, as compared with positive controls. There was no incidence of tumor formation at the 20 nmol/L concentration of baicalein. To examine protection against UVB-induced tumor promotion by baicalein, tumors were first initiated in mice using the chemical 7,12-dimethylbenz[a]anthracene (DMBA). Tumors were then promoted over the study period with a previously established tumor-promoting dose of UVB, administered after application of low- or high-dose baicalein. Baicalein exhibited a dose-dependent protective effect against UVB-induced tumor promotion, with low-dose baicalein, decreasing tumor incidence by 45% (P \.05) and tumor multiplicity by 82.3% (P \.05) and high-dose baicalein decreasing tumor incidence and multiplicity by 60% (P \.05) and 92.2% (P \.05), respectively, as compared with positive controls.
SIMULTANEOUS APPEARANCE OF LEG GIANT SQUAMOUS CELL CARCINOMA AND ECTOPIC PHEOCHROMOCYTOMA Anto´nio Luı´s Santos, MD, Marta Pereira, MD, Dermatology and Venereology Department, S. Joa˜o Hospital, Oporto, Portugal; Jesus Ventura, MD, Cirurgia A Department, S. Joa˜o Hospital, Oporto, Portugal; Teresa Baudrier, MD, Dermatology and Venereology Department, S. Joa˜o Hospital, Oporto, Portugal A 36-year-old male patient presented with a tumoral exophytic ulcerated lesion on the right leg of 1 month’s duration. The patient had had recurrent leg ulceration since 18 years of age when he was diagnosed with psoriasiformis dermatitis. At initial observation, the patient had a wasting syndrome, acute hypertension, and bilateral inguinal lymph node enlargement.
Our results suggest that topical application of baicalein protects against both UVBinduced tumor initiation and promotion.
Hematological study showed hypochromic microcytic anemia requiring several blood transfusions. In the 24-hour urine collection elevated norepinephrine and metanephrine were found. Bacteriological examination of the swab from the ulcer’s surface revealed Pseudomonas aeruginosa. Several samples of tissue from different locations were collected. Polymerase chain reaction analysis for Mycobacterium tuberculosis DNA was negative. One of the samples revealed squamous cell carcinoma (SCC) with moderate differentiation. Findings of renal ultrasonography, computed tomography of the thoracic and abdominal-pelvic area, and adrenal magnetic resonance imaging were normal. The patient underwent amputation of the right leg proximal to the knee and bilateral inguinal lymph node dissection. No metastasis was found. After surgery, blood pressure and urinary catecholamine levels returned to normal, which may, in our opinion, suggest local tumoral endocrine production. During the past 6 months the patient recovered very well; both clinical and laboratory parameters normalized. Historically, SCC has been associated with chronic ulcers and/or infections. In our case the giant aspect of the lesion, along with the rapid evolution and endocrine abnormalities, make it an atypical case. Nothing to disclose.
Nothing to disclose.
P2309 SCLEROTIC BASAL CELL CARCINOMA TREATED WITH IMIQUIMOD 5% CREAM Nicole Pace, MD, Joanne Brown, M. Shane Chapman, MD, DartmouthHitchocock Medical Center, Lebanon, NH, United States Introduction: Imiquimod 5% cream has been shown to eradicate superficial basal cell carcinoma and nodular basal cell carcinoma. These rates may vary depending on frequency and duration of treatment. Most case reports and studies excluded the more aggressive histologic subtypes, such as morpheaform and sclerotic basal cell carcinoma. The rate of clearance of these tumors with imiquimod is unclear. We report 3 cases of sclerotic basal cell carcinoma treated with imiquimod 5% cream. Methods: We chose 3 patients with sclerotic basal cell carcinoma to undergo therapy with imiquimod 5% cream daily for up to 12 weeks. A 3-mm punch biopsy followed at 4 weeks after the final dose. Results: In 2 of the 3 patients (cases 1 and 2) sclerotic basal cell carcinoma cleared clinically and histologically (3-mm punch biopsy) after daily treatment for 12 weeks. One of these 2 patients required a 3- to 4-day rest period because of intense inflammation. In the patient in case 3, sclerotic basal cell carcinoma failed to clear. Discussion: Imiquimod is an imidazoquinoline immune response modifier, originally intended to treat external genital warts. The drug acts through the Toll-like receptor 7, which is followed by the stimulation of the NF-kB and the Jnk signal transduction pathway. This causes release of various Th1 cytokines, including interleukin 12, interferon alfa, interferon-g, tumor necrosis factor-a, and many others. This collection of cytokines seems to stimulate the cellular immune response, augmenting the eradication of warts, molluscum, actinic keratosis, and superficial and nodular basal cell carcinoma. Sclerotic basal cell carcinoma poses a special problem in that these tumors can be more aggressive and more difficult to eradicate. For these reasons, Mohs micrographic surgery is the standard of care. However, there are patients who do not want Mohs surgery or are poor surgical candidates. Since imiquimod has been successful at eradicating a majority of superficial and nodular basal cell carcinomas, we thought it might also be effective for sclerotic basal cell carcinoma. Conclusion: Mohs micrographic surgery remains the standard of care for sclerotic basal cell carcinoma. However, in poor surgical candidates, it is possible to eradicate some (but not all) sclerotic basal cell carcinomas with imiquimod 5% cream. In our opinion, imiquimod is a reasonable secondary, nonsurgical option for sclerotic basal cell carcinoma. Dr. Chapman is a consultant and speaker and has performed clinical trials for 3M Pharmaceuticals.
MARCH 2005
P2311 STUDY OF THE CORRELATION AMONG P53 EXPRESSION, EPIDERMAL HYPERPLASIA, DERMAL INFLAMMATION, P21 EXPRESSION, AND KI-67 EXPRESSION IN ACTINIC KERATOSIS Young Hyun Joo, In Ho Kwon, MD, Kwang Hyun Cho, MD, Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Background: Actinic keratosis is a proliferation of transformed neoplastic keratinocytes that are confined to the epidermis; it is induced by exposure to UV radiation in sunlight. The neoplastic transformation is primarily due to p53 gene mutation. Objective: Our purposes were to study the correlation among p53 expression, epidermal hyperplasia, dermal inflammation, Ki-67 expression, and p21 expression in actinic keratosis. Methods: We reviewed histopathologic slides of 21 cases of actinic keratosis. We performed immunoperoxidase staining using monoclonal antibody to p53 protein, Ki-67 antigen, and p21 protein on the specimen. We statistically analyzed the correlation among p53 expression, epidermal hyperplasia, and dermal inflammation, Ki-67 expression, and p21 expression. Results: We found higher expression of p53 in the actinic keratosis with a hyperplastic epidermis, but this finding was not statistically significant (P = .233). There was no correlation between the expression level of p53 and the severity of dermal inflammation (P = .755). The expression level of p53 had significant positive correlation with the expression level of Ki-67 (P = .001). There was no correlation between the expression level of p53 and that of p21 (P = .116). Conclusion: We observed that p53 expression had significant positive correlation to only Ki-67 expression. We suggested that further study would be needed on the correlation among p53 expression, epidermal hyperplasia, dermal inflammation, and p21 expression in actinic keratosis. Nothing to disclose.
J AM ACAD DERMATOL
P149
P2310
PROTECTIVE EFFECTS OF BAICALEIN AGAINST THE INITIATION AND PROMOTION OF CARCINOGENESIS BY ULTRAVIOLET B RADIATION IN MICE Arash Akhavan, MD, Huachen Wei, MD, PhD, The Mount Sinai School of Medicine, New York, NY, United States Baicalein, a flavonoid isolated from the plant Scutellaria baicalensis, has been shown to have anticancer properties in cultured cell and animal models. We used two doses of baicalein in an animal model of Skh-1 hairless mice to investigate the inhibition of ultraviolet B (UVB)-generated tumor initiation and promotion. To study protection against UVB initiation of tumors, mice were first treated with either low-dose (5 nmol/L) or high-dose (20 nmol/L) baicalein, followed by a previously established tumor-initiating dose of UVB. Tumorigenesis was then promoted with a course of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Application of baicalein caused a dose-dependent decrease in UVB-induced tumor initiation. Application of low-dose baicalein reduced tumor incidence and multiplicity by 63.2% (P \ .05) and 79.7% (P \ .05), respectively, as compared with positive controls. There was no incidence of tumor formation at the 20 nmol/L concentration of baicalein. To examine protection against UVB-induced tumor promotion by baicalein, tumors were first initiated in mice using the chemical 7,12-dimethylbenz[a]anthracene (DMBA). Tumors were then promoted over the study period with a previously established tumor-promoting dose of UVB, administered after application of low- or high-dose baicalein. Baicalein exhibited a dose-dependent protective effect against UVB-induced tumor promotion, with low-dose baicalein, decreasing tumor incidence by 45% (P \.05) and tumor multiplicity by 82.3% (P \.05) and high-dose baicalein decreasing tumor incidence and multiplicity by 60% (P \.05) and 92.2% (P \.05), respectively, as compared with positive controls.
SIMULTANEOUS APPEARANCE OF LEG GIANT SQUAMOUS CELL CARCINOMA AND ECTOPIC PHEOCHROMOCYTOMA Anto´nio Luı´s Santos, MD, Marta Pereira, MD, Dermatology and Venereology Department, S. Joa˜o Hospital, Oporto, Portugal; Jesus Ventura, MD, Cirurgia A Department, S. Joa˜o Hospital, Oporto, Portugal; Teresa Baudrier, MD, Dermatology and Venereology Department, S. Joa˜o Hospital, Oporto, Portugal A 36-year-old male patient presented with a tumoral exophytic ulcerated lesion on the right leg of 1 month’s duration. The patient had had recurrent leg ulceration since 18 years of age when he was diagnosed with psoriasiformis dermatitis. At initial observation, the patient had a wasting syndrome, acute hypertension, and bilateral inguinal lymph node enlargement.
Our results suggest that topical application of baicalein protects against both UVBinduced tumor initiation and promotion.
Hematological study showed hypochromic microcytic anemia requiring several blood transfusions. In the 24-hour urine collection elevated norepinephrine and metanephrine were found. Bacteriological examination of the swab from the ulcer’s surface revealed Pseudomonas aeruginosa. Several samples of tissue from different locations were collected. Polymerase chain reaction analysis for Mycobacterium tuberculosis DNA was negative. One of the samples revealed squamous cell carcinoma (SCC) with moderate differentiation. Findings of renal ultrasonography, computed tomography of the thoracic and abdominal-pelvic area, and adrenal magnetic resonance imaging were normal. The patient underwent amputation of the right leg proximal to the knee and bilateral inguinal lymph node dissection. No metastasis was found. After surgery, blood pressure and urinary catecholamine levels returned to normal, which may, in our opinion, suggest local tumoral endocrine production. During the past 6 months the patient recovered very well; both clinical and laboratory parameters normalized. Historically, SCC has been associated with chronic ulcers and/or infections. In our case the giant aspect of the lesion, along with the rapid evolution and endocrine abnormalities, make it an atypical case. Nothing to disclose.
Nothing to disclose.
P2309 SCLEROTIC BASAL CELL CARCINOMA TREATED WITH IMIQUIMOD 5% CREAM Nicole Pace, MD, Joanne Brown, M. Shane Chapman, MD, DartmouthHitchocock Medical Center, Lebanon, NH, United States Introduction: Imiquimod 5% cream has been shown to eradicate superficial basal cell carcinoma and nodular basal cell carcinoma. These rates may vary depending on frequency and duration of treatment. Most case reports and studies excluded the more aggressive histologic subtypes, such as morpheaform and sclerotic basal cell carcinoma. The rate of clearance of these tumors with imiquimod is unclear. We report 3 cases of sclerotic basal cell carcinoma treated with imiquimod 5% cream. Methods: We chose 3 patients with sclerotic basal cell carcinoma to undergo therapy with imiquimod 5% cream daily for up to 12 weeks. A 3-mm punch biopsy followed at 4 weeks after the final dose. Results: In 2 of the 3 patients (cases 1 and 2) sclerotic basal cell carcinoma cleared clinically and histologically (3-mm punch biopsy) after daily treatment for 12 weeks. One of these 2 patients required a 3- to 4-day rest period because of intense inflammation. In the patient in case 3, sclerotic basal cell carcinoma failed to clear. Discussion: Imiquimod is an imidazoquinoline immune response modifier, originally intended to treat external genital warts. The drug acts through the Toll-like receptor 7, which is followed by the stimulation of the NF-kB and the Jnk signal transduction pathway. This causes release of various Th1 cytokines, including interleukin 12, interferon alfa, interferon-g, tumor necrosis factor-a, and many others. This collection of cytokines seems to stimulate the cellular immune response, augmenting the eradication of warts, molluscum, actinic keratosis, and superficial and nodular basal cell carcinoma. Sclerotic basal cell carcinoma poses a special problem in that these tumors can be more aggressive and more difficult to eradicate. For these reasons, Mohs micrographic surgery is the standard of care. However, there are patients who do not want Mohs surgery or are poor surgical candidates. Since imiquimod has been successful at eradicating a majority of superficial and nodular basal cell carcinomas, we thought it might also be effective for sclerotic basal cell carcinoma. Conclusion: Mohs micrographic surgery remains the standard of care for sclerotic basal cell carcinoma. However, in poor surgical candidates, it is possible to eradicate some (but not all) sclerotic basal cell carcinomas with imiquimod 5% cream. In our opinion, imiquimod is a reasonable secondary, nonsurgical option for sclerotic basal cell carcinoma. Dr. Chapman is a consultant and speaker and has performed clinical trials for 3M Pharmaceuticals.
MARCH 2005
P2311 STUDY OF THE CORRELATION AMONG P53 EXPRESSION, EPIDERMAL HYPERPLASIA, DERMAL INFLAMMATION, P21 EXPRESSION, AND KI-67 EXPRESSION IN ACTINIC KERATOSIS Young Hyun Joo, In Ho Kwon, MD, Kwang Hyun Cho, MD, Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Background: Actinic keratosis is a proliferation of transformed neoplastic keratinocytes that are confined to the epidermis; it is induced by exposure to UV radiation in sunlight. The neoplastic transformation is primarily due to p53 gene mutation. Objective: Our purposes were to study the correlation among p53 expression, epidermal hyperplasia, dermal inflammation, Ki-67 expression, and p21 expression in actinic keratosis. Methods: We reviewed histopathologic slides of 21 cases of actinic keratosis. We performed immunoperoxidase staining using monoclonal antibody to p53 protein, Ki-67 antigen, and p21 protein on the specimen. We statistically analyzed the correlation among p53 expression, epidermal hyperplasia, and dermal inflammation, Ki-67 expression, and p21 expression. Results: We found higher expression of p53 in the actinic keratosis with a hyperplastic epidermis, but this finding was not statistically significant (P = .233). There was no correlation between the expression level of p53 and the severity of dermal inflammation (P = .755). The expression level of p53 had significant positive correlation with the expression level of Ki-67 (P = .001). There was no correlation between the expression level of p53 and that of p21 (P = .116). Conclusion: We observed that p53 expression had significant positive correlation to only Ki-67 expression. We suggested that further study would be needed on the correlation among p53 expression, epidermal hyperplasia, dermal inflammation, and p21 expression in actinic keratosis. Nothing to disclose.
J AM ACAD DERMATOL
P149