• Title, Summary, Keyword: tumor immunotherapy

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The long-term prognostic impact of sentinel lymph node biopsy in patients with primary cutaneous melanoma: a prospective study with 10-year follow-up

  • Portinari, Mattia;Baldini, Gabriele;Guidoboni, Massimo;Borghi, Alessandro;Panareo, Stefano;Bonazza, Simona;Dionigi, Gianlorenzo;Carcoforo, Paolo
    • Annals of Surgical Treatment and Research
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    • v.95 no.5
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    • pp.286-296
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    • 2018
  • Purpose: Sentinel lymph node (SLN) biopsy (SLNB) is widely accepted for staging of melanoma patients. It has been shown that clinico-pathological features such as Breslow thickness, ulceration, age, and sex are better predictors of relapse and survival than SLN status alone. The aims of this study were to evaluate the long-term (10-year) prognostic impact of SLNB and to determine predictive factors associated with SLN metastasis, relapse, and melanoma specific mortality (MSM). Methods: This was a prospective observational study on 289 consecutive patients with primary cutaneous melanoma who underwent SLNB from January 2000 to December 2007, and followed until January 2014, at an Italian academic hospital. Results: SLN was positive in 64 patients (22.1%). The median follow-up was 116 months (79-147 months). Tenyear disease-free survival and melanoma specific survival were poor in patients with positive SLN (58.7% and 66.4%, respectively). Only the increasing Breslow thickness resulted independently associated to an increased risk of SLN metastasis. Cox regression analysis showed that a Breslow thickness >2 mm was an independent predictor of relapse, and male sex and Breslow thickness >2 mm was a predictor of MSM. At 10 years, SLN metastasis was not significantly associated to either relapse or MSM. Conclusion: After the fifth year of follow-up, SLN metastasis is not an independent predictive factor of relapse or mortality which are mainly influenced by the characteristics of the primary tumor and of the patient. Patients with a Breslow thickness >2 mm regardless of the SLN status should be considered at high risk for 10-year relapse and mortality.

miR-195/miR-497 Regulate CD274 Expression of Immune Regulatory Ligands in Triple-Negative Breast Cancer

  • Yang, Lianzhou;Cai, Yuchen;Zhang, Dongsheng;Sun, Jian;Xu, Chenyu;Zhao, Wenli;Jiang, Wenqi;Pan, Chunhua
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.371-381
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    • 2018
  • Purpose: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. Methods: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. Results: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3' untranslated region. Conclusion: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.

Diagnostic Utility of MAGE Expression in Exudative Pleural Effusion (삼출성 흉수에서 악성 감별을 위한 MAGE 유전자 검출의 의의)

  • Kim, Kyung Chan;Seo, Chang Gyun;Park, Sun Hyo;Choi, Won-Il;Han, Seung Beom;Jeon, Young June;Park, Jong-Wook;Jeon, Chang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.2
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    • pp.159-168
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    • 2004
  • Background : In recent years, numerous human tumor specific antigens such as melanoma antigen gene(MAGE) that is recognized by autologous cytotoxic T lymphocytes have been identified. MAGE is expressed in many human malignancies in various organs, such as lung, breast, stomach, esophagus and leukemia. Therefore MAGE has been studied widely for tumor diagnosis and immunotherapy. But, so far there were no clinical studies evaluating the role of MAGE in pleural effusion. We investigated the expression of MAGE in the patients with exudative pleural effusion for it's diagnostic utility and the results were compared with those of cytologic examinations. Methods : Diagnostic thoracentesis was performed in 44 consecutive patients with exudative pleural effusion during 6 months. We examined the expression of MAGE and cytology with the obtained pleural effusion. Expression of MAGE was interpreted by means of a commercial kit using RT-PCR method. Enrolled patients were divided into two groups such as malignant and benign and we analyzed its' sensitivity and specificity. Results : There were no significant differences between two groups in age, sex, white blood cell counts in pleural fluid, pleural fluid/serum protein ratio and pleural fluid/serum LDH ratio. The sensitivity and specificity of MAGE were 72.2% and 96.2% respectively and the positive predictive value and negative predictive value of MAGE were also 92.9% and 83.3% respectively. The sensitivity and negative predictive value of cytologic examinations were 66.7% and 81.3% respectively. There were no significant differences between sensitivities of MAGE and cytologic examinations but false positive result of MAGE was found in 1 case of tuberculous pleurisy. Conclusion : MAGE is a sensitive and specific marker for the differential diagnosis between benign and malignant effusion in patients with exudative pleural effusion. And MAGE would provide the equal sensitivity compared with that of cytologic examination in patients with malignant pleural effusion if 5mL of the pleural fluid is examined.