Ultrasound-guided needle biopsy of large thyroid nodules: Core needle biopsy yields more reliable results than fine needle aspiration.

PURPOSE: The objective of this study was to compare the false negative rate, sensitivity and false positive rate of ultrasound (US)-guided fine needle aspiration (FNA) with those of US-guided core needle biopsy (CNB) for large thyroid nodules ≥2.0 cm, which reportedly have an increased risk of thyroid malignancy. METHODS: We retrospectively studied surgically confirmed thyroid nodules that had preoperative US-guided FNA or CNB between March 2005 and December 2013. We reviewed nodule size, sonographic features, cytohistologic results, and final surgical pathology. We assessed false negative rates, sensitivity, and false positive rates by biopsy method and nodule size for diagnosis of thyroid malignancy. We assessed complications for procedures. RESULTS: US-guided CNB showed better diagnostic performance, in terms of lower false negative rates and greater sensitivity, than US-guided FNA in large thyroid nodules. There was no significant difference in false positive rate according to biopsy methods in large thyroid nodules. The false negative rates of large thyroid nodules (≥2.0 cm) were higher than those of small nodules (<2.0 cm). There were no major complications, and no significant differences in complication according to biopsy methods. CONCLUSION: US-guided CNB improved the false negative rate and sensitivity for large nodules. Therefore, US-guided CNB can be considered a useful diagnostic method for large thyroid nodules that might reduce the risk of unnecessary diagnostic surgery.

Pulsed and color Doppler sonographic findings of penile Mondor's disease.

This report describes the color and pulsed Doppler US findings of penile Mondor's disease. The pulsed Doppler US findings of penile Mondor's disease have not been previously published, so we report here for the first time on the cavernosal arterial flow signal pattern of penile Mondor's disease. Penile Mondor's disease is rare disease that's characterized by thrombosis in the dorsal vein of the penis. The previous reports on penile Mondor's disease are concerned with the color Doppler US finding without the flow signals in this area, but these findings are insufficient to understand the hemodynamics in penile Mondor's disease. We report for the first time on a cavernosal artery flow signal pattern of low peak systolic velocity and high-resistance.

The Flavonoid Jaceosidin from Artemisia princeps Induces Apoptotic Cell Death and Inhibits the Akt Pathway in Oral Cancer Cells.

Jaceosidin is a single compound from the Japanese mugwort Artemisia princeps, which is used as a food and a traditional medicinal herb. A. princeps extracts and flavonoid components have been shown to have antihyperglycaemic, antioxidant, and anti-inflammatory properties. Although the anticancer properties of these extracts were recently demonstrated, the related mechanisms have not been characterised. In this study, we investigated the effects of jaceosidin in oral squamous cell carcinoma (OSCC) cells and initially showed selective suppression of proliferation (IC50 = 82.1 µM in HSC-3 cells and 97.5 µM in Ca9.22 cells) and accumulation of cells at the sub-G1 stage of the cell cycle. In addition, jaceosidin increased cleavage of caspase-9 and caspase-3 in OSCC cells, although caspase-8 was not detected. In further experiments, jaceosidin downregulated Akt phosphorylation and ectopic activation of Akt blocked the antiproliferative effects of jaceosidin. Finally, we showed that jaceosidin has no effects on HaCaT normal epithelial cell viability, indicating selective chemotherapeutic potential of jaceosidin and that tumour-specific downregulation of Akt increases apoptosis and inhibits growth in OSCC cells.

Anti-inflammatory activity of Kochia scoparia fruit on contact dermatitis in mice.

The mature fruit of Kochia scoparia (L.) Schrad. is widely administered in China and Korea as a medicinal herb for treatment of skin diseases, diabetes mellitus and rheumatoid arthritis. The present study investigated the effects of methanol extracts of K. scoparia dried fruit (MEKS) on ear swelling, histopathological changes (such as epidermal acanthosis, spongiosis and immune cell infiltration) and cytokine production in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mice. Topical application of MEKS inhibited DNFB-induced ear thickness and weight increases, as well as DNFB-induced epidermal acanthosis, spongiosis and immune cell infiltration. In addition, treatment with MEKS significantly decreased the levels of tumor necrosis factor-α, interferon-γ and monocyte chemotactic protein-1 in inflamed tissues. These data indicate that the mature fruit of K. scoparia has the potential to be administered for the treatment of inflammatory skin diseases and that the anti-inflammatory action of K. scoparia is involved in the inhibition of type 1 T helper cell skewing reactions.

Kochia scoparia induces apoptosis of oral cancer cells in vitro and in heterotopic tumors.

ETHNOPHARMACOLOGICAL RELEVANCE: Kochia scoparia grows commonly in China, Japan, and Korea and its mature fruit has been used throughout the area in traditional medicine to treat diseases including skin problems and inflammatory and allergic disease. More importantly, Kochia scoparia has been prescribed to treat the malignant tumor of head and neck region and breast mass. Although it has been proposed as an anti-cancer agent for several cancers, its exact in vivo anti-cancer properties and the molecular mechanisms underlying its effects are poorly understood. AIM OF THE STUDY: To evaluate the anti-cancer activity of the methanol extract of K. scoparia, mature fruit (MEKS) on oral squamous cell carcinoma (OSCC) and to explore its mode of action. MATERIALS AND METHODS: To assess proliferation inhibition and apoptosis induction by MEKS, MTT assays, cell analysis, ANNEXIN V and PI double staining, and Hoechst 33342 staining were performed. The activation of caspases and the MAP kinase p38 was evaluated using Western blot analysis. The anti-cancer properties of MEKS in vivo were elucidated in a heterotopic OSCC animal model. RESULTS: After OSCC cells were treated with MEKS, the numbers of sub-G1 accumulated cells and apoptotic bodies increased, indicating that MEKS inhibited OSCC cell proliferation selectively through induction of apoptosis. Apoptosis of MEKS-treated OSCC cells was induced in a dose-dependent manner by caspase-3 and -9 activation. In addition, pretreatment with p38 inhibitor SB203580 in combination with MEKS significantly prevented MEKS-induced apoptosis in OSCC cells and also decreased cleaved capase 3, 9, and cleaved PARP activity in western blotting. MEKS treatment significantly increased the apoptosis of OSCC and inhibited tumour growth in our animal model. CONCLUSION: Taken together, these results indicated that MEKS induced apoptosis of OSCC cells through caspase activation involving the p38 MAPK pathway. MEKS could be a promising anti-cancer candidate for OSCC treatment.

Poncirus trifoliata Rafin. induces the apoptosis of triple-negative breast cancer cells via activation of the c-Jun NH(2)-terminal kinase and extracellular signal-regulated kinase pathways.

BACKGROUND: Poncirus trifoliata Rafin. is a traditional medicine with known anti-inflammatory and anti-cancer properties. Traditionally, it is used to control chronic inflammation, allergy and gastrointestinal diseases such as digestive ulcers gastritis in China, Japan, and Korea. OBJECTIVES: To evaluate the apoptosis-inducing activity of a P. trifoliata methanol extract (MEPT) and elucidate the molecular mechanisms. MATERIALS AND METHODS: The anti-cancer effect of MEPT and its underlying mechanisms were investigated in breast cancer cells using 3,4,5-dimethyl N-methylthiazol-2-yl-2, 5-d-phenyl tetrazolium bromide assay, cell cycle analysis, and western blotting. RESULTS: MEPT suppressed the proliferation of MDA-MB-231 cells with inhibition dose 50% value of 119.44 µg/mL at 24 h, which have features typical of triple-negative breast cancer cells. MEPT also altered the characteristic features of the MDA-MB-231 cells and increased the proportion of cells undergoing sub-G1 arrest. In addition, MEPT increased levels of caspase 8 and 3 in MDA-MB-231 cells, whereas caspase 9 was not detected. In addition, MEPT-induced tumor necrosis factor receptor (TNFR) and TNFR type 1-associated death domain (TRADD) protein and the activations of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK). CONCLUSION: Our results indicate that MEPT has chemotherapeutic potential in triple-negative breast cancer and that at the molecular level its effects are derived from the activations of TNFR and of the mitogen-activated protein kinase pathway.

Effects of Dictamnus dasycarpus Turcz., root bark on ICAM-1 expression and chemokine productions in vivo and vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: The root bark of Dictamnus dasycarpus Turcz., family Rutaceae is a well known anti-inflammatory agent for skin diseases such as eczema, pruritus and urticaria in Eastern countries. MATERIALS AND METHODS: We investigated the effects of methanol extract of Dictamnus dasycarpus root bark (MEDD) on Intercellular Adhesion Molecule-1 (ICAM-1) expression, epidermal hyperplasia and immune cell infiltration in 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis (CD) mice. We also investigated its effects on the expression of ICAM-1, binding capacity to THP-1 cells, cytokine and chemokine production, and phosphorylation of NF-κB in human keratinocytes (HaCaT cells). RESULTS: Topical application of MEDD effectively inhibited ICAM-1 expression and epidermal hyperplasia in inflamed tissues. MEDD treatment also inhibited immune cell infiltration induced by DNFB. In addition, treatment with MEDD reduced surface expression and total amount of ICAM-1in HaCaT cells and effectively lowered the capacity to bind to THP-1 cells. MEDD also lowered the levels of IL-6, IL-8, monokine induced by gamma interferon (MIG), monocyte chemotactic protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES). Finally, MEDD treatment prevented activation of the NF-κB pathway induced by TNF-α in HaCaT cells. CONCLUSIONS: These data indicate that root bark of Dictamnus dasycarpus has the potential for treatment of inflammatory skin diseases as a complementary or alternative medicine to corticosteroids. In addition, they suggest that the anti-inflammatory effects of Dictamnus dasycarpus on CD are involved in the regulation of ICAM-1 expression and cytokine and chemokine secretion through down-regulation of the NF-κB signaling pathway in keratinocytes.

Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental Medicine, in Human Oral Cancer HSC-4 Cells.

Poncirus trifoliata Rafin. has long been used as anti-inflammatory and antiallergic agent to treat gastrointestinal disorders and pulmonary diseases such as indigestion, constipation, chest fullness, chest pain, bronchitis, and sputum in Korea. P. trifoliata extract has recently been reported to possess anticancer properties; however, its mechanisms of action remain unclear. In this study, its antiproliferative effects and possible mechanisms were investigated in HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 µg/mL) in a dose-dependent manner. While there were no significant changes observed upon cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated groups, the intensity of acidic vesicular organelle (AVO) staining and microtubule-associated protein 1 light chain (LC) 3-II protein expression increased in response to MEPT treatment. Furthermore, 3-methyladenine (3-MA, autophagy inhibitor) effectively blocked the MEPT-induced cytotoxicity of HSC-4 cells and triggered the activation of p38 and extracellular signal-regulated kinases (ERK) proteins. Taken together, our results indicate that MEPT is a potent autophagy agonist in oral cancer cells with antitumor therapeutic potential that acts through the mitogen-activated protein kinase (MAPK) pathway.

Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells.

BACKGROUND: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. OBJECTIVE: To investigate the anti-cancer effect of K. scoparia on breast cancer. MATERIALS AND METHODS: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS) in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS) generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. RESULTS: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC50 value of 36.2 µg/ml. MEKS at 25 µg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose) polymerase (PARP). CONCLUSION: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

Sulfasalazine induces autophagic cell death in oral cancer cells via Akt and ERK pathways.

Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1- LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.

Risk prediction for malignant conversion of oral epithelial dysplasia by hypoxia related protein expression.

AIMS: Increased aerobic glycolysis is a unique finding in cancers and hypoxia-related proteins are associated with aerobic glycolysis. Therefore, we aimed to investigate whether hypoxia-related proteins can be predictive markers for malignant conversion of oral premalignant lesions with epithelial dysplasia (OED). METHODS: Expression of HIF-1α, Glut-1 and CA9 were detected in clinical samples of eight normal oral mucosa, 85 transitional areas of oral squamous cell carcinoma (OSCC) and 28 OED with or without malignant conversion using immunohistochemistry and were also comparatively detected in immortalised human oral keratinocyte (IHOK) and OSCC cell lines under hypoxia using immunoblotting. RESULTS: Sequential expression of HIF-1α, Glut-1 and CA9 was found both in transitional areas of OSCC and cell lines of IHOK and OSCC under hypoxia, supporting hypoxia-aerobic glycolysis-acidosis axis. Expression of all proteins showed significant association with malignant conversion of OED and CA9 was an independent risk factor of malignant transformation of OED. But the predictability of malignant transformation was improved when all three proteins were applied together. CONCLUSION: High expression of CA9 was an independent predictive marker of malignant conversion. Moreover, the combined application of these three proteins may be useful to assess the risk of malignant conversion of OED.

Epigenetic alteration of PRKCDBP in colorectal cancers and its implication in tumor cell resistance to TNFα-induced apoptosis.

PURPOSE: PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis. EXPERIMENTAL DESIGN: Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-κB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays. RESULTS: PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G(1) cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFα, and its level correlated with tumor cell sensitivity to TNFα-induced apoptosis. PRKCDBP induction by TNFα was disrupted by blocking NF-κB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFα, and this response was abolished by disruption of a κB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFα-induced apoptosis. CONCLUSIONS: PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-κB in response to TNFα. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFα and other stresses, particularly under chronic inflammatory microenvironment.