• Title/Summary/Keyword: Small cell melanoma

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Expression of Nuclear Factor Erythroid 2 Protein in Malignant Cutaneous Tumors

  • Choi, Chang Yong;Kim, Jin Young;Wee, Seo Yeong;Lee, Jang Hyun;Nam, Doo Hyun;Kim, Chul Han;Cho, Moon Kyun;Lee, Yoon Jin;Nam, Hae Seon;Lee, Sang Han;Ch, Sung Woo
    • Archives of Plastic Surgery
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    • v.41 no.6
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    • pp.654-660
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    • 2014
  • Background Reactive oxygen species (ROS) damages cell molecules, and modifies cell signaling. The nuclear factor E2-related factor (Nrf2) is a critical transcription regulator, which protects cells against oxidative damage. Nrf2 expression is increased in a large number of cancers. However, little information has been reported regarding the expression of Nrf2 in skin cancers. Hence, we explored the expression of Nrf2 protein in skin cancers. Methods The Nrf2 protein expression in 24 specimens, including 6 malignant melanomas (MM), 6 squamous cell carcinomas (SCC), 6 basal cell carcinomas (BCC), and 6 normal skin tissues, was evaluated by western blotting. Immunohistochemical staining was performed. The expression of Kelch-like ECH-associated protein 1 (Keap1), the key regulator of Nrf2, was also analyzed by western blotting. Results Small interfering RNA transfection to the melanoma cell line G361 confirmed that an approximately 66 kDa band was the true Nrf2 band. The western blot revealed that the Nrf2 protein was definitely expressed in normal skin tissues, but the Nrf2 expression was decreased in MM, SCC, and BCC. Immunohistochemical examination showed that expression of Nrf2 was decreased in all skin cancer tissues compared to the normal skin tissues. Keap1 was not expressed in all malignant skin tumors and normal skin tissues by western blot. Conclusions ROS was increased in various types of cancers which proteins were highly expressed or underexpressed. This study demonstrated that the expression of Nrf2 protein was down-regulated in human malignant skin tumors. We suggest that decreased expression of Nrf2 is related to skin cancers.

Changes of Serum soluble ICAM-1 levels in Patients with Lung Cancer (폐암 환자에서 혈청 soluble ICAM-1농도의 변화)

  • Yoo, Wan Hee;Lee, Yong Chul;Rhee, Yang Keun
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.527-535
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    • 1996
  • Background : Cell adhesion molecules knave been Implicated In the various stages of tumor progression and metastasis. ICAM-1 plays a important roles in cell-cell interactions in inflammatory and immune response of several diseases. Recently, elevated levels of sICAM-1 in circulation was reported as association with liver metastasis in gastric, Colonic, gall bladder and pancreatic cancer, with reduced survival in malignant melanoma. This study was performed to measure the sICAM-1 in patients with lung cancer and to evaluate the relations between staging of lung cancer and level of sICAM-1. Methods : Serum sICAM-1 was measured in 36 patients with lung cancer according to the pathologic types and clinical staging before therapy and in 8 controls with ICAM-1 ELISA kit. Results : Serum sICAM-1 levels were elevated in patients with lung cancer except small cell type. Also progression and metastasis of lung cancer associated with elevation of sICAM-1 levels. Conclusion : These results suggest that higher levels of serum ICAM-1 reflect the progression and metastasis of lung cancer and it may be used as a marker with diagnostic and prognostic significance.

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Relation between ERCC1 Expression in Sputum and Survival after Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (비소세포 폐암환자의 객담 내 ERCC1 발현정도와 cisplatin 복합화학요법 후 치료반응)

  • Yang, Sung Woo;Choi, Pyoung Rak;You, Hong Jun;Kim, Jin Gu;Oak, Chul Ho;Jang, Tae Won;Jung, Maan Hong
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.151-159
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    • 2006
  • Background : Excision repair cross complementing gene 1 (ERCC1) not only has a protective role against carcinogens, but plays an important role in cisplatin-resistance via the repair of cisplatin-DNA adducts. This study investigated the association between the ERCC1 expression levels in sputum and survival after cisplatin-based chemotherapy in patients with inoperable non-small cell lung cancer (NSCLC). Methods : Using the sputum collected from 67 inoperable (stage IIIa-IV) NSCLC patients treated with either taxanes (33 cases) or gemcitabine (34 cases) plus cisplatin, the relative expression levels of ERCC1 and the expression of the tumor specific antigen, MAGE, were examined by the quantitative RT-PCR and RT-PCR, respectively. The response and survival were compared with the relative level of ERCC1 or MAGE expression and the treatment modality. Results : In the sputum, ERCC1 and MAGE was detected in 74.6% and 40.2% of patients, respectively. Using the median ERCC1 level, the patients were classified as having high or low ERCC1 expression. The median overall survival (MST) was significantly longer in patients with a high ERCC1 expression level than those with a low expression level (84 weeks vs. 44 weeks respectively, P=0.017). In the taxene-based treatment group, the MST was longer than the gemcitabine group (79 weeks vs. 47 weeks, respectively, P=0.03). The levels of ERCC1 were significantly higher in patients who were MAGE-positive (P=0.003). In the MAGE-negative patients, the MST was longer in the high ERCC1 group (103 weeks vs. 43 weeks, P=0.008), but not in the MAGE-positive patients (62 weeks vs. 44 weeks, P=0.348). Conclusion : ERCC1 expression in the sputum can be a prognostic factor for survival after chemotherapy in patients with inoperable NSCLC.

Potentiality of Anti-idiotypic Antibodies Mimicking GD2 to Induce Cellular Immunity (GD2 유사 항이디오타입 항체의 세포면역 유발 잠재성)

  • Park, Yoon-Sun;Shin, Woon-Seob
    • IMMUNE NETWORK
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    • v.4 no.4
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    • pp.229-236
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    • 2004
  • Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma, small cell lung carcinoma and neuroblastoma. Immunity against GD2 has anti-tumor activities, but GD2 is poorly immunogenic. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In our previous study, we produced anti-idiotypic antibodies mimicking GD2 (3A4 and 3H9), which induced humoral immunity. However, cellular immunity is essential to eradicate tumor cells in vivo as well as humoral immunity. In the present study, we investigated whether these anti-idiotypic antibodies 3A4 and 3H9 could induce cellular immunes responses. Methods: BALB/C mice were immunized with anti-idiotypic antibody 3A4 or 3H9, or normal mouse IgG as a negative control. Lymphoproliferative responses, cytokine production responses, and delayed-type hypersensitivity reactions were measured in mice immunized with the anti-idiotypic antibodies. Results: Both the anti-idiotypic antibody 3A4 and 3H9 induced GD2-specific lymphoproliferative responses and $IFN-{\gamma}$ production of lymph node lymphocytes in BALB/C mice. Only anti-idiotypic antibody 3H9 induced significant GD2-specific delayed-type hypersensitivity in the mice. Conclusion: These results show that anti-idiotypic antibodies 3A4 and 3H9 have the potentiality of inducing GD2-specific cellular immune responses that cannot be induced by the native antigen GD2 itself.

Production of Lignin Peroxidase by Phellinus igniarius and Cytotoxic Effects of Lignin Hydrolysates Derived from Wood Biomass on Cancer Cells

  • Lee, Jae-Sung;Lee, Jong-Suk;Yoon, Jae-Don;Beak, Sung-Mok;Bosire, Kefa-O.;Lee, Yong-Soo;Kim, Jung-Ae
    • Biomolecules & Therapeutics
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    • v.12 no.3
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    • pp.189-193
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    • 2004
  • Over the past several years, research efforts have been directed both at economically producing valuable substances from the wood biomass and at producing lignolytic enzymes at a lower cost. In the present study, we found that Phellinus igniarius, the basidiomycetes, secreted lignin peroxidase as a main lignolytic enzyme, which was detected maximum activity at 16th day of culture and showed 37 kDa of molecular mass in identification by activity assay and purification by anion-exchange chromatography. The Phellinus igniarius-derived lignin peroxidase hydrolyzed steam-exploded wood (Quercus mongolica) powder into small molecules showing cytotoxicity against cancer cel1s (HepG2 hepatoma, SK-N-SH neuroblastoma, B16 melanoma, MBT-2 bladder cancer). In addition, the enzyme hydrlysates of lignins (ELg) that were extracted from the steam-exploded oak showed more potent cytotoxic effects on the cancer cells than the enzyme hydrolysates of wood biomass (EWp), indicating that the cytotoxic effect of EWp may be due to the enzyme-degraded products of lignin among the lignocellulosics. Furthermore, the cytotoxic effect of ELg on Chang, normal liver cells, was much less potent than that of ELg on HepG2 and B16 cancer cells, indicating that the cytotoxic effect of ELg may be specific for cancer cells. The present results suggest that Phellinus igniarius may be a useful resource for the large-scale production of lignin peroxidase and that the lignin peroxidase may be applied for the generation of valuable biodegradation products from wood lignocellulosics for medical use.

Biotransformation of Intestinal Bacterial Metabolites of Ginseng Saponin to Biologically Active Fatty-acid Conjugates

  • Hasegawa Hideo;Saiki Ikuo
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.317-334
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    • 2002
  • Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.

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The Utility of MAGE Gene Detection in Bronchial Washing Fluid for Patients with Peripheral NSCLC (말초 비소세포폐암 환자에서 기관지 세척액 MAGE 유전자 진단의 유용성)

  • Kim, Suhyun;Kim, Hojoong;Kwon, O Jung;Chung, Man Pyo;Suh, Gee Young;Koh, Won-Jung;Ham, Cho Rom;Nam, Hae Seong;Um, Sang-Won;Kwon, Yong Soo;Park, Sung-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.1
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    • pp.15-21
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    • 2008
  • Background: The melanoma antigen-encoding (MAGE) genes are known to be expressed in various cancer cells, including non-small cell lung cancer (NSCLC), and are silent in all normal tissues except for the testis. In patients with peripheral NSCLC, bronchial washing fluid can be used to detect the MAGE genes, suggesting a diagnosis of lung cancer. In order to evaluate the diagnostic utility of the MAGE test in patients with peripheral NSCLC, bronchial washing fluid was investigated in patients with peripheral pulmonary nodules, which were invisible as detected by bronchoscopy. Methods: Bronchial washing fluid from 37 patients was used for cytological examinations and MAGE gene detection, using RT-nested-PCR of common A1-A6 mRNA. Results were compared to a final diagnosis of patients as confirmed by pathology. Results: Among the 37 subjects, NSCLC was diagnosed in 21 patients, and benign pulmonary diseases were diagnosed in 16 patients. MAGE mRNA was detected in 10 of 21 (47.6%) NSCLC patients, while conventional cytology examinations were positive for MAGE expression in 2 of 21 (9.5%) cases. MAGE expression was observed in 4 of 16 (25%) benign pulmonary disease patients. Conclusion: The MAGE test of bronchial washing fluid can be used as a sensitive predictor of peripheral NSCLC patients.

Preparation of Natural Compounds-tripeptides Derivatives and Their Melanogensis Inhibitory Activity (천연유래물질 펩타이드 유도체의 제조와 멜라닌 생성 저해 효과 탐색)

  • Shin, Kyong-Hoon;Lee, Jae-Ho;Ryu, Geun-Seok;Jee, Kyung-Yup;Park, Soo-Nam;Kim, Jae-Il;Cho, In-Shik;Kim, Han-Young
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.36 no.3
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    • pp.233-240
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    • 2010
  • Derivatives of a novel natural compunds, melanostatin (PLG-$NH_2$) were prepared by solid phase synthesis[1,2] and assayed to evaluate their melanogensis inhibitory activity. Also, a small library (natural compound-XLG-$NH_2$, natural compound-X LG-OH) was prepared with same method for increasing synthetic yield and cost-reduction. PLG-$NH_2$ (Proline-Leucine-Glycine-$NH_2$) was well-known tripeptide as its $\alpha$-MSH release-inhibiting activity and tyrosinase inhibitory activity[3-5]. In order to choose best candidate for peptide derivatization, various natural compounds were screened by their tyrosinase inhibitory activity. As a result, caffeic acid and coumaric acid were selected. Most of these derivatives showed better activities than the parent natural compound, melanostatin.

The Usefulness of $^{18}F-FDG $ PET as a Cancer Screening Test ($^{18}F-FDG $ PET의 암 선별검사로서의 유용성)

  • Ko, Doo-Heun;Choi, Joon-Young;Song, Yun-Mi;Lee, Su-Jin;Kim, Young-Hwan;Lee, Kyung-Han;Kim, Byung-Tae;Lee, Moon-Kyu
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.6
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    • pp.444-450
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    • 2008
  • Purpose: The aim of this study was to evaluate the usefulness of whole body positron emission tomography (PET) using $^{18}F-fluorodeoxyglucose$ ($^{18}F-FDG$) for cancer screening in asymptomatic subjects. Materials and Methods: The subjects were 1,762 men and 259 women who voluntarily underwent $^{18}F-FDG$ PET for cancer screening as a part of a routine health examination. Final diagnosis was decided by other diagnostic studies, pathological results or clinical follow-up for 1 year. Results: Of 2,021 subjects, 40 (2.0%) were finally proved to have cancer. Abnormal focal $^{18}F-FDG$ uptake suggesting malignancy was found in 102 subjects (5.0%). Among them, 21 subjects (1.0%) were proved to have cancer. Other tests in the routine health examination could not find 9 of 21 cancers (42.9%) detected by PET. The sensitivity, specificity, positive predictive value, and negative predictive value of PET for cancer screening were 52.5%, 95.9%, 20.6%, and 99.0%, respectively. Pathologies of cancers missed on PET were adenocarcinoma (n = 9; 3 colon cancers, 3 prostate cancers, 2 stomach cancers, and 1 rectal cancer), differentiated thyroid carcinoma (n = 6), bronchioalveolar cell carcinoma (n = 2), urinary bladder cancer (n = 1), and melanoma (n = 1). More than half of cancers which were not detected by PET were smaller than 1 cm in diameter. Conclusion: $^{18}F-FDG$ PET might be useful for cancer screening in asymptomatic subjects due to its high specificity and negative predictive value and playa supplementary role to the conventional health check-up, but it could not replace due to limited sensitivity for urological cancers, small-sized tumors and some hypometaboic cancers.

Current Status and Future Perspective of PET (PET 이용 현황 및 전망)

  • Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.1-7
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    • 2002
  • Positron Emission Tomography (PET) is a nuclear medicine imaging modality that consists of systemic administration to a subject of a radiopharmaceutical labeled with a positron-emitting radionuclide. Following administration, its distribution in the organ or structure under study can be assessed as a function of time and space by (1) defecting the annihilation radiation resulting from the interaction of the positrons with matter, and (2) reconstructing the distribution of the radioactivity from a series of that used in computed tomography (CT). The nuclides most generally exhibit chemical properties that render them particularly desirable in physiological studies. The radionuclides most widely used in PET are F-18, C-11, O-15 and N-13. Regarding to the number of the current PET Centers worldwide (based on ICP data), more than 300 PET Centers were in operation in 2000. The use of PET technology grew rapidly compared to that in 1992 and 1996, particularly in the USA, which demonstrates a three-fold rise in PET installations. In 2001, 194 PET Centers were operating in the USA. In 1994, two clinical and research-oriented PET Centers at Seoul National University Hospital and Samsung Medical Center, was established as the first dedicated PET and Cyclotron machines in Korea, followed by two more PET facilities at the Korea Cancer Center Hospital, Ajou Medical Center, Yonsei University Medical Center, National Cancer Center and established their PET Center. Catholic Medical School and Pusan National University Hospital have finalized a plan to install PET machine in 2002, which results in total of nine PET Centers in Korea. Considering annual trends of PET application in four major PET centers in Korea in Asan Medical Center recent six years (from 1995 to 2000), a total of 11,564 patients have been studied every year and the number of PET studies has shown steep growth year upon year. We had 1,020 PET patients in 1995. This number increased to 1,196, 1,756, 2,379, 3,015 and 4,414 in 1996,1997,1998,1999 and 2000, respectively. The application in cardiac disorders is minimal, and among various neuropsychiatric diseases, patients with epilepsy or dementia can benefit from PET studios. Recently, we investigated brain mapping and neuroreceptor works. PET is not a key application for evaluation of the cardiac patients in Korea because of the relatively low incidence of cardiac disease and less costly procedures such as SPECT can now be performed. The changes in the application of PET studios indicate that, initially, brain PET occupied almost 60% in 1995, followed by a gradual decrease in brain application. However, overall PET use in the diagnosis and management of patients with cancer was up to 63% in 2000. The current medicare coverage policy in the USA is very important because reimbursement policy is critical for the promotion of PET. In May 1995, the Health Care Financing Administration (HCFA) began covering the PET perfusion study using Rubidium-82, evaluation of a solitary pulmonary nodule and pathologically proven non-small cell lung cancer. As of July 1999, Medicare's coverage policy expanded to include additional indications: evaluation of recurrent colorectal cancer with a rising CEA level, staging of lymphoma and detection of recurrent or metastatic melanoma. In December of 2001, National Coverage decided to expand Medicare reimbursement for broad use in 6 cancers: lung, colorecctal, lymphoma, melanoma, head and neck, and esophageal cancers; for determining revascularization in heart diseases; and for identifying epilepsy patients. In addition, PET coverage is expected to further expand to diseases affecting women, such as breast, ovarian, uterine and vaginal cancers as well as diseases like prostate cancer and Alzheimer's disease.