No Evidence of Abnormal Expression of Beta-Catenin and Bcl-2 Proteins in Pilomatricoma as One Clinical Feature of Tetrasomy 9p Syndrome.

BACKGROUND: Little is currently known about the genetics of pilomatricoma. A number of studies have reported some evidence that this disease may have a genetic association with mutations of CTNNB1 gene or expression of the beta-catenin protein. In this study, we reviewed literatures involving 30 patients with various genetic syndromes that have been linked to pilomatricoma and found that somatic mutations of the CTNNB1 gene were reported in 67% of patients. Pilomatricoma has been reported in patients with chromosome 9 rearrangements, including 4 patients with tetrasomy 9p syndrome and one patient with partial trisomy 9. In addition to beta-catenin, the expression of bcl2 was observed in pilomatricoma. OBJECTIVES: To report an additional case of tetrasomy 9p syndrome with concurrent pilomatricoma and to examine whether abnormal protein expressions of the CTNNB1 and/or BCL2 genes were present. METHODS: Cytogenetic analysis was carried out on peripheral blood, biopsied skin, and pilomatricoma tissue obtained from a patient with tetrasomy 9p syndrome. Immunohistochemical staining was performed on the pilomatricoma tissue, using beta-catenin and bcl2 monoclonal antibodies. RESULTS: SNP microarray revealed nonmosaic gain of the short arm of chromosome 9. A nonmosaic isodicentric chromosome 9 was identified in the peripheral blood but this rearranged chromosome was detected in only 8.3% of the skin fibroblasts. Chromosomal abnormalities were not detected in the pilomatricoma nor expression of beta-catenin or bcl2 proteins in our patient. CONCLUSION: Pilomatricoma could be a new clinical feature associated with tetrasomy 9p syndrome; however, we found no evidence of tetrasomy 9p or abnormal beta-catenin or bcl2 proteins of the CTNNB1 and BCL2 genes in our pilomatricoma patient.

Comparative Inhibitory Efficacy on the iNOS/NO System of Curcuminand Tetrahydrocurcumin-Self-Microemulsifying Liquid Formulation in Chronic Gastric Ulcer Model.

BACKGROUND: Curcumin was found to accelerate gastric ulcer healing by the main mechanism, i.e., the suppression of iNOS mediated inflammation. Although Tetrahydrocurcumin (THC) is claimed to be an active antioxidant element of curcumin, its antiulcer activity has not been systematically examined. The utility of Self-Microemulsifying Drug Delivery Systems (SMEDDSs) for curcumin and THC formulations in the liquid form was also found to increase the rate and extent of release of curcumin- and THC-SMEDDS. Nevertheless, the beneficial antiulcer effect of these nanoproducts has not yet been evaluated. OBJECTIVE: This study aimed to evaluate and compare the antiulcer efficacy of curcumin- and THCSMEDDS through the inhibition of the iNOS/NO system in the rat model. METHODS: Antiulcer efficacy was compared in terms of the ability to accelerate healing of gastric ulcer including the efficient inhibitory action on inflammatory NO production in activated macrophages and iNOS mRNA expression at the ulcerated area. RESULTS: THC was found to have less ulcer healing capacity than curcumin with a lack of significant inhibitory effect on the iNOS/NO system. The SMEDDS used in the study significantly increased the inhibitory efficacy of THC on iNOS/NO production and iNOS mRNA expression compared to the inhibitory potency of curcumin. An oral administration of curcumin- or THC-SMEDDS once a day was appropriate for exerting a comparable curative efficacy to a twice-daily oral administration of curcumin or THC. CONCLUSION: The SMEDDS used in the study was observed to enhance the inhibitory efficacy of the antiulcer drug on the iNOS/NO system, leading to a reduction of daily dosing and dosing frequency.

Clonal relationship of synchronous head and neck cancer and esophageal cancer assessed by single nucleotide polymorphism-based loss of heterozygosity analysis.

BACKGROUND: The prognoses of head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC) are poor, especially when both tumors occur at the same time. We examined the clonal relatedness of HNSCCs with synchronous ESCCs to confirm whether the second tumors were metastasis or separate second primary malignancies (SPMs) using loss of heterozygosity (LOH) analysis. METHODS: Twenty-one pairs of formalin-fixed paraffin-embedded tissue from HNSCC patients with synchronous esophageal cancer were analyzed by single nucleotide polymorphism (SNP) array using the Illumina HumanCytoSNP FFPE-12 BeadChip (San Diego, CA), which contains approximately 300,000 probes. LOH was identified using Nexus Copy Number software (El Segundo, CA). RESULTS: Comparing the LOH pattern between HNSCC and paired ESCC, we found that 20 out of 21 paired tissues had a high number of discordant LOHs (LOH identified solely in the primary HNSCC but not in synchronous ESCC at the same genomic location) and a low number of concordant LOHs (LOH at the same genomic location in both HNSCC and ESCC). Only one case fell into the undetermined category. Therefore, these 20 ESCCs were classified as SPMs or second field tumors (SFTs). Moreover, the HNSCC patients with molecularly confirmed esophageal SPM had significantly poorer survival than the other patients. CONCLUSIONS: We propose the use of a genome-wide SNP array as a tool to differentiate metastatic tumors from SPM/SFT. The SNP array offers genome-wide LOH information that earlier microsatellite analysis studies lack. The ability to accurately identify SPM should contribute to a better treatment plan and follow-up care of these patients.

Correlation between Serum SCCA and CYFRA 2 1-1, Tissue Ki-67, and Clinicopathological Factors in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67) in ESCC patients. OBJECTIVE: To study the correlation between SCCA, CYFRA 21-1, Ki-67, and clinicopathological factors in ESCC patients. MATERIAL AND METHOD: Pretreatment SCCA and CYFRA 21-1 serum levels were measured, while the expression of Ki-67 was assessed on tumor tissue. The associations between these biomarkers, clinicopathological factors, and overall survival were analyzed. RESULTS: One hundred sixty six patients participated in this study. Elevated SCCA and CYFRA 21-1 were found in 78.9% and 50.0% of the patients, respectively, while 42.8% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p = 0.128) to each other nor to age, sex, T N, M location, grade, or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p = 0.010), M1 (p = 0.010), and poor grade (p = 0.015) but not to age, sex, N, or location. Levels of SCCA, CYFRA 21-1, and Ki-67, alone or in any combination, were not correlated to survival of patients. CONCLUSION: The authors showed that Ki-67 in tumor tissue is probably a more reliable marker than serum SCCA and CYFRA 21-1 in predicting the clinical course of ESCC.

Wound healing activities of standardized pomegranate rind extract and its major antioxidant ellagic acid in rat dermal wounds.

The in vivo wound healing potential of a standardized pomegranate rind extract (SPRE) and its major antioxidant constituent, ellagic acid (EA, 13 %, w/w), were investigated in three rat dermal wound models. It was found that both SPRE (5 and 2.5 %) and its equivalent amount of EA (0.65 and 0.325 %) increased the tensile strength of the incision wound by a maximum of 35.43 and 31.82 %, respectively. SPRE at 5 and 2.5 % accelerated wound contraction of the excision wound and the burn wound, while EA was effective only at 0.65 % in these two wound models. Further assays revealed that SPRE enhanced the synthesis of collagen by a maximum of 21.83 mg/g and inhibited neutrophil infiltration dose-dependently, while EA was not effective in increasing collagen accumulation and its inhibitory effect on neutrophil infiltration was milder. These results indicated that SPRE is a promising phytopharmaceutical effective in facilitating the healing of wounds and is superior to its marker compound EA.

Unusual presentation of giant cell tumor originating from a facet joint of the thoracic spine in a child: a case report and review of the literature.

INTRODUCTION: Giant cell tumor of the synovium is a common benign lesion that frequently occurs at the tendon sheaths in the hand; it is usually found in adults over 30 years old. It is related to pigmented villonodular synovitis. Giant cell tumor of the synovium or pigmented villonodular synovitis has been described rarely in the axial skeleton especially in the thoracic vertebrae of a child. CASE PRESENTATION: A previously healthy 7-year-old Thai girl presented with back pain and progressive paraparesis and was unable to walk for 1 month. She had weakness and hyperreflexia of both lower extremities. Magnetic resonance imaging showed a well-defined homogeneously and intensely enhanced extradural mass with cord compression at T4 to T7 levels. The patient underwent laminectomy at T4 through to T7 and total tumor removal. Permanent histopathologic sections and immunostains revealed a giant cell tumor of the synovium. Postoperative neurological status recovered to grade V. Magnetic resonance imaging at the 1-year follow-up showed no recurrence and there was no clinical recurrence at the 2-year follow-up. CONCLUSION: We report an extremely rare case of giant cell tumor in the epidural space that extended from a thoracic facet joint. The tumor was removed successfully through laminectomies. Although giant cell tumor of a facet joint of the thoracic spine is very rare, it must be considered in the differential diagnosis for masses occurring in the epidural space in a child. Total tumor removal is the best treatment. Careful monitoring of recurrence can achieve a good clinical outcome.

Topical anti-inflammatory and analgesic activities of standardized pomegranate rind extract in comparison with its marker compound ellagic acid in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: In Chinese traditional medicine, the peels of Punica granatum L. have been used to treat traumatic hemorrhage, burn, and ulcers. AIMS OF THE STUDY: This study aimed to assess the topical anti-inflammatory and analgesic activities of a standardized pomegranate rind extract (SPRE) of which ellagic acid (EA) was the major antioxidant constituent and the marker compound. MATERIAL AND METHODS: The topical anti-inflammatory effects of SPRE were evaluated against acute models (croton oil-induced mouse ear edema and carrageenan-induced rat paw edema) and chronic model (complete Freund's adjuvant (CFA)-induced polyarthritis). The topical analgesic activities of SPRE were investigated in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test. All studies of SPRE were carried out in parallel with its marker compound EA. RESULTS: SPRE (5%, 2.5%, and 1%, w/w) and the equivalent EA (0.65%, 0.325%, and 0.13%, w/w) dose-dependently reduced the croton oil-induced mouse ear edema with a maximal inhibition of 86.30% and 80.82%, respectively. SPRE dose-dependently attenuated the inflammatory responses in the carrageenan-induced rat paw edema and in the CFA-induced polyarthritis but the equivalent EA were effective only at the doses of 0.65% and 0.325%. Both SPRE (5%) and EA (0.65%) showed significant topical analgesic activities in the rat punctuate mechanical hyperalgesia test and in the mouse formalin test. CONCLUSIONS: SPRE was more active as an anti-inflammatory agent than EA. The anti-inflammatory and analgesic effects of SPRE were achieved through inhibiting the leukocyte infiltration and modulating the pro-inflammatory cytokines IL-ß and TNF-α. These results clearly demonstrated that SPRE is a promising phytomedicine that could find use in the treatment of inflammatory diseases.