SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

A Novel Long-Acting Glucagon-Like Peptide-1 Agonist with Improved Efficacy in Insulin Secretion and beta-Cell Growth

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by cleavage of proglucagon in intestinal L-cells. In the pancreas, GLP-1 stimulates post-prandial insulin secretion, promotes insulin biosynthesis, and improves insulin sensitivity. Because of its insulinotropic activity, GLP-1 has been considered a good candidate drug for treatment of diabetes mellitus. However, clinical use of GLP-1 has been limited by its short half-life, as a result of rapid degradation by dipeptidyl peptidase-IV (DPP-IV). METHODS: We designed a novel GLP-1 analog, Xenopus GLP-1 (xGLP)-E4. The Ala residue in the second position of xGLP was replaced with a Ser residue to increase the half-life in the body. The C-terminal tail of exendin-4 was added to enhance the binding affinity for the GLP-1 receptor (GLP1R). The potency of GLP-1 and its analogs was determined by luciferase assay. The stability of GLP1R agonists was evaluated by determining the activity of agonists that had been preincubated in the presence of fetal bovine serum, which contains innate DPP-IV activity. The effects of xGLP-E4 on insulin secretion and beta-cell growth were investigated using insulin enzyme-linked immunosorbent assay and cell counting. RESULTS: xGLP-E4 exhibited improved stability against DPP-IV activity and increased potency to GLP1R, compared with GLP-1. An increase in glucose-dependent insulin secretion was observed in xGLP-E4-treated pancreatic beta-cells. The effect of xGLP-E4 on beta-cell growth was greater than that of GLP-1. CONCLUSION: We developed a novel GLP-1 analog, xGLP-E4, that shows prolonged longevity and improved efficacy. This analog is a potential candidate for treatment of type 2 diabetes.

A Statistical Survey of Major Cutaneous Malignant Tumors for the Last 10 Years (2000~2010, North-east Gyeonggido Province) / 대한피부과학회지

BACKGROUND: Major cutaneous malignant tumors (MCMT) including squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and malignant melanoma (MM) result from multifactorial causes such as environmental and host factors. In particular, ultraviolet radiation (UVR) comprised of environmental factors is estimated to be one of the most important risk factors for MCMT. OBJECTIVE: The purpose of this study was to analyze recent changes in the incidence of MCMT in patients from the north-east area of gyeonggido, and compare that incidence with data previously reported. METHODS: We retrospectively reviewed the medical records of 212 patients diagnosed as MCMT at the Department of Dermatology at the Uijeongbu St. Mary's Hospital during the last 10 years. RESULTS: The average annual incidence of MCMT was 0.3% and it seemed to increase. Among the 212 cases of malignant tumors, the most common malignant tumor was BCC (62.7%). The incidence of SCC and MM were 25% and 12.3%, respectively. The mean age of patients was 68.4+/-14.15 years for those with MCMT; 66.8 y in BCC, 74.5 y in SCC and 64.5 y in MM. The ratio of men to women was 0.72:1. Compared with the incidence of MCMT in other provinces, the north-east portion of Gyeonggido (0.3%) had a high incidence of MCMT. CONCLUSION: High altitude may increase the amount of UVR exposure and influence the development of cutaneous malignant tumors. Individual behaviors including outdoor activity and use of sun blocks are important to the development of major cutaneous tumors and should not be ignored.

Aquagenic Urticaria: A Report of Two Cases

Aquagenic urticaria is a rare form of physical urticaria, in which contact with water evokes wheals. A 19-year-old man and a 4-year-old boy complained of recurrent episodes of urticaria. Urticaria appeared while taking a bath or a shower, in the rain, or in a swimming pool. Well-defined pin head to small pea-sized wheals surrounded by variable sized erythema were provoked by contact with water on the face, neck, and trunk, regardless of its temperature or source. Results from a physical examination and a baseline laboratory evaluation were within normal limits. Treatment of the 19-year-old man with 180 mg fexofenadine daily was successful to prevent the wheals and erythema. Treatment with 5 ml ketotifen syrup bid per day resulted in improvement of symptoms in the 4-year-old boy.

Primary Granulocytic Sarcoma of the Face

Myeloid sarcoma is a tumor which consists of myeloblasts or immature myeloid cells. This tumor presents in the lymphoid organs, bone, skin, soft tissue, various mucosae and organs, and the central nervous system. Granulocytic sarcoma, an extramedullary acute myeloid leukemia, is also referred to as chloroma (GS) because of its greenish surface color. Granulocytic sarcoma is rare and difficult to diagnose. We can easily misdiagnose this tumor as lymphoma or sarcoma, especially when there is no evidence of hematologic disorders. Immunohistochemical studies are helpful in determining the correct diagnosis. Antibodies to myeloperoxidase, lysozyme, and chloroacetate esterase are used for the diagnosis of granulocytic sarcoma. In addition, detection of cell surface markers such as CD 33, CD 34, CD 68, CD 99, and HLA-DR may be useful. We describe a case of GS that presented with bluish nodules on the right cheek of a 54-year-old woman with immunohistochemical findings for correct diagnosis.

A Case of Mucinous Eccrine Carcinoma of the Skin / 대한피부과학회지

Mucinous eccrine carcinoma of the skin is a rare skin adnexal malignant tumor that origins from mucin-secreting dark cells, and it arises from the deepest portion of eccrine ducts. It usually affects people in their fifth to seventh decades of life and it predominantly occurs in men. It appears to exhibit a predilection for the head and neck. The histopathologic characteristics are a large mucinous pool with fibrous septae and clusters of tumor cells. The treatment of choice is surgical removal. We present here the case of a patient with a mucinoous eccrine carcinoma on the infraorbital area of the right side of his face and we review the related literature

A Case of Granular Cell Tumor of the Scalp / 대한피부과학회지

Granular cell tumors are rare disease can be which found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen on the scalp. We report here on a rare case of granular cell tumor on the scalp. A 55-year-old woman presented with a non-tender, firm papule on the scalp. We removed the papule with excisional biopsy. Histopathologic examination showed well-circumscribed, non-capsulated nodule that consisted of large polygonal cells with abundant eosinophilic granular cytoplasms. The tumor cells were positive for S-100 protein staining. We diagnosed this case as granular cell tumor.

Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice

Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.