Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Anticancer Activity of Indeno1,2-b-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.

Kikuchi Disease Manifesting as Multifocal Lymphadenopathy and Splenomegaly: Ultrasonography, CT, and 18F-FDG PET/CT Findings Mimicking Lymphoma

Kikuchi disease is a type of benign, self-limiting necrotizing lymphadenitis that occurs most commonly in young women and usually manifests as palpable cervical lymph nodes and fever. Patients with an unusual location of lymph node involvement can be misdiagnosed with malignant disease. Here, we report a case of Kikuchi disease in a 15-year-old girl presenting with persistent fever for 2 weeks. Imaging studies, including ultrasonography, CT, and 18F-fluorodeoxyglucose PET/CT, revealed splenomegaly and enlarged lymph nodes in the neck, axilla, abdomen, retroperitoneum, and inguinal region. Laparoscopic excision of the celiac lymph nodes confirmed histiocytic necrotizing lymphadenitis, also known as Kikuchi disease. Conservative treatment with corticosteroids improved the patient's condition.

YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.

HIFU: Effects and Clinical Effectiveness of Non-surgical Therapy for Uterine Fibroids

No abstract available.

Erratum to: HIFU: Effects and Clinical Effectiveness of Non-surgical Therapy for Uterine Fibroids

Author's list and affiliation correction.

Inhibitory Effect of 3-(4-Hydroxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one, a Chalcone Derivative on MCP-1 Expression in Macrophages via Inhibition of ROS and Akt Signaling

Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-kappaB (NF-kappaB) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.

Ewing's Sarcoma/Primitive Neuroectodermal Tumor of the Uterine Corpus

No abstract available.

Metastatic malignant melanoma with peritoneal seeding in a young woman: A case report

Malignant melanomas of the uterus, either primary or metastatic, are extremely rare. They can be mistaken as other tumors, such as uterine sarcomas during diagnosis. We describe here the first case of a metastatic melanoma of the uterus with peritoneal seeding in a young woman. It was first diagnosed as a uterine sarcoma from a frozen-section biopsy.

TI-I-174, a Synthetic Chalcone Derivative, Suppresses Nitric Oxide Production in Murine Macrophages via Heme Oxygenase-1 Induction and Inhibition of AP-1

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-alpha), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-kappaB (NF-kappaB) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.

Impact of Chemoradiation on Prognosis in Stage IVB Cervical Cancer with Distant Lymphatic Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to determine whether chemoradiation (CCR) is efficient for improving prognosis, compared with systemic chemotherapy (SC), in patients with stage IVB cervical cancer who have distant lymphatic metastasis. MATERIALS AND METHODS: Among 2,322 patients with cervical cancer between January 2000 and March 2010, 43 patients (1.9%) had stage IVB disease. After exclusion of 19 patients due to insufficient data and hematogenous metastasis, 24 patients (1%) who received CCR (n=10) or SC (n=14) were enrolled. We compared tumor response, progression-free survival (PFS) and overall survival (OS), and disease recurrence between CCR and SC. RESULTS: Complete response rates were 60% and 0% after CCR and SC (p<0.01). Grade 3 or 4 leukopenia was more common in patients treated with CCR (24.4% vs. 9.1%, p=0.03), whereas grade 3 or 4 neuropenia was more frequent in those treated with SC (28.4% vs. 11.1%, p=0.03). Development of grade 3 proctitis occurred as a late radiotherapy (RT)-related toxicity in only one patient (10%) treated with CCR. In addition, squamous cell carcinoma and CCR were favorable prognostic factors for improvement of PFS (adjusted hazard ratios [HRs], 0.17 and 0.12; 95% confidence intervals [CIs], 0.04 to 0.80 and 0.03 to 0.61), and only CCR was significant for improvement of OS (adjusted HR, 0.15; 95% CI, 0.02 to 0.90). However, no differences in the rate and pattern of disease recurrence were observed between CCR and SC. CONCLUSION: CCR may be more effective than SC for improving survival, and can be regarded as a feasible method with some caution regarding late RT-related toxicity for treatment of stage IVB cervical cancer with distant lymphatic metastasis.

A case of secondary syphilis presenting as multiple pulmonary nodules

Syphilis is a sexually transmitted disease caused by Treponema pallidum. The prevalence of this disease has recently increased worldwide. However, pulmonary involvement in secondary syphilis is extremely rare. A 51-year-old heterosexual male patient presented with multiple pulmonary nodules with reactive serology from the Venereal Disease Research Laboratory test and positive fluorescent treponemal antibody absorption testing. A hematogenous metastatic malignancy was suspected and an excisional lung biopsy was performed. Histopathological examination showed only central necrosis with abscess and plasma cell infiltration, but no malignant cells. The patient reported sexual contact with a prostitute 8 weeks previously and a penile lesion 6 weeks earlier. Physical examination revealed an erythematous papular rash on the trunk. Secondary syphilis with pulmonary nodules was suspected, and benzathine penicillin G, 2.4 million units, was administered. Subsequently, the clinical signs of syphilis improved and the pulmonary nodules resolved. The final diagnosis was secondary syphilis with pulmonary nodular involvement.

Small Bowel Carcinoma in Young Patient Detected by Double-balloon Enteroscopy / 대한소화기학회지

A 17-year old female presented with a chief complaint of melena and epigastric pain. She had a family history of colon cancer, her mother having been diagnosed with hereditary nonpolyposis colorectal carcinoma (HNPCC). After close examination including double-balloon enteroscopy, the patient was diagnosed with small bowel carcinoma, in spite of her young age. Here we report this rare case of small bowel carcinoma in a young patient with a family history of HNPCC.

Adnexal Clear Cell Carcinoma with Comedonecrosis: A Case Report

Adnexal clear cell carcinoma with comedonecrosis (ACCCC) is a very rare malignancy of the skin with an aggressive clinical course and a predilection for the scalp. This is the first reported case of ACCCC in Korea. A 79-year-old male presented with left abdominal masses that proved to be two subcutaneous nodules. The tumors histologically consisted of epithelial nests that showed a distinctive zonal arrangement. The centrally located clear cell areas with comedonecroses were merged with the peripheral squamoid cells, often exhibiting retraction artifacts and an infiltrating border. Nuclear pleomorphism and frequent mitoses were prominent. The clear cells were immunopositive for carcinoembryonic antigen and epithelial membrane antigen. We report here on a case of ACCCC involving the abdominal skin, and this tumor should be distinguished from the more indolent squamous cell and tricholemmal carcinomas.

Expression of p16, Rb and FHIT Proteins in Urothelial Carcinoma of the Urinary Bladder

BACKGROUND: The goal of this study was to investigate the expression of p16, retinoblastoma (Rb) and fragile histidine triad (FHIT) proteins in urothelial carcinomas of the urinary bladder, and to evaluate the relationship between clinicopathlogic parameters and each protein expression level. METHODS: The expression of p16, Rb, and FHIT proteins were studied in 176 patients with urothelial carcinoma of the urinary bladder by immunohistochemistry. RESULTS: The diffuse positive expression of the p16 protein was significantly associated with high grade and advanced tumor depth (p=0.007 and p=0.020). The loss of the Rb protein was significantly associated with old age and disease recurrence (p=0.020 and 0.037). The loss of the FHIT protein was significantly associated with advanced tumor depth (p=0.002). CONCLUSION: Our data suggest that p16 and FHIT proteins may be involved in the progression of urothelial carcinoma. In addition, p16 may be a useful prognostic marker for individual urothelial carcinoma patients.

Comparison of Sporadic Sclerotic Fibroma and Solitary Fibrous Tumor in the Oral Cavity

Sporadic sclerotic fibroma (SF) and solitary fibrous tumor (SFT) arising in the oral cavity are very rare. In this report, we describe two cases of oral pathology, one involving SF and the other involving SFT. Both cases presented with well- circumscribed, firm nodules with similar gross findings. However, the histologic findings of the SF and SFT showed rather distinct features. The SF was composed of hyalinized sclerotic collagen bundles arranged in a whorled pattern, whereas the SFT was formed by spindles cells arranged in hypo- and hypercellular areas. The immunohistochemical findings were similar in both cases; there was positivity for vimentin, CD34, and CD99, but bcl-2 positivity was only seen in the SFT. Although their histopathologies are similar, SF and SFT should be considered in the differential diagnosis of soft tissue tumors in the oral cavity.

Sclerosing Mucoepidermoid Carcinoma of the Parotid Gland: A Case Report

Sclerosing mucoepidermoid carcinoma (SMEC) is a very rare tumor of the salivary gland. There have been eight cases of SMEC reported in the medical literature; this is the first reported case in Korea. A 51-year-old woman presented with a right infra-auricular mass that she had for 3 years. We performed superficial parotidectomy. Grossly, the resected parotid gland showed a well-circumscribed firm mass. Histologically, the tumor consisted of central solid or ductal tumor nests within a dense fibrous stroma surrounded by peripheral lymphoid infiltration. The tumor nests were composed of squamous, intermediate and mucin-secreting cells. However, the tumor cells lacked mitosis and nuclear anaplasia. The lymphoid cells were mostly composed of lymphocytes and plasma cells with occasional eosinophils and neutrophils. Immunohistochemically, the tumor cells were positive for high- and low- molecular weight cytokeratins, cytokeratin 7, p16INK4A, Bcl-2 and cyclin D1. The patient also underwent radiation therapy. We report here on a case of SMEC of the parotid gland along with the immunohistochemical characteristics, and we review the relevant literature.

Granular Cell Tumors of the Abdominal Wall

Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non-tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm.

Granular Cell Tumors of the Abdominal Wall

Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non-tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm.

Usefulness of High-Frequency Compound Spatial Sonography in the Assessment of Hepatitis B Virus Related Chronic Liver Disease

PURPOSE: To evaluate the liver parenchyma according to the echo patterns of CSS (compound spatial sonography), and to correlate them with the extent of hepatic fibrosis and the serum aminotransferase level. MATERIALS AND METHODS: The CSS images were classified into the following three echo patterns: type I, a normallooking echo; type II, hyperechoic or hypoechoic nodules scattered in a normal-looking echo; type III, a severely heterogeneous echogenic or hypoechoic honeycomb-like echo. The CSS findings were correlated with the histopathology findings in 63 patients with HBV. The serum aminotransferase levels and the occurrence of acute exacerbation in 168 patients with HBV, with and without a progressed parenchymal echo pattern, and who were followed up more than 1-year period, were compared. The interobserver agreement between the two radiologists for assessing the parenchymal echo pattern was scored. RESULTS: The correlation between the CSS pattern and hepatic fibrosis was statistically significant (correlation coefficient = 0.58, p < 0.05). The baseline serum aminotransferase level was not significantly different between the patients with and without a progressed parenchymal echo pattern. However, the rate of acute exacerbation was higher in patients with a progressed parenchymal echo pattern (p < 0.05). The interobserver agreement was good (k statistic = 0.63, 0.78). CONCLUSION: The liver parenchymal pattern based on the 5-12 MHz CSS is a useful and objective tool for diagnosing and monitoring HBV related chronic liver disease.