Archives

  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • br Predictive or prognostic biomarkers that test for express

    2020-08-30


    Predictive or prognostic biomarkers that test for EPZ 31686 of a gene that is regulated at the level of transcriptional control can be challenging, as they can often result in patchy variable expression detected on immunohistochemistry and do not al-low for testing for genetic changes in equivocal cases. To ad-dress this challenge, we studied a panel of 6 immunohistochemistry markers involved in colonic differenti-ation. We found that CDX2 status in isolation may have lim-ited utility in routine practice to assess for risk in colon cancer. However, Muc2 was identified as a potential marker for prognostication in CRC in our cohort and in gene expres-sion data obtained from the TCGA; the combination of both CDX2 and Muc2 gene expression status was able to identify patients with a worse overall survival and increased rate of dis-ease recurrence from the TCGA database.
    A reproducible but small effect of CDX2 status has been identified in stage II colon cancer patients [6,15,42]; however, our work suggests that Muc2 may be a more effective means of prognostication. Instead of focusing on the expression of one marker by immunohistochemistry, it may be more accu-rate and reproducible to assess gene expression signatures to identify cases of CRC with a more undifferentiated phenotype as reported initially EPZ 31686 [5]. As next-generation sequencing and RNA-based testing become more prevalent in routine surgical pathology, there may be opportunities to capitalize on this technology to design further trials revising and better defining our prognostic and predictive tools in CRC.
    References
    [3] Benson AB, Schrag D, Somerfield MR, et al. American Society of Clin-ical Oncology recommendations on adjuvant chemotherapy for stage II 
    [5] Merlos-Suárez A, Barriga FM, Jung P, et al. The intestinal stem cell sig-
    CDX2 and Muc2 in stage II colon cancer 79
    [24] Minoo P, Zlobec I, Peterson M, Terracciano L, Lugli A. Characteriza-tion of rectal, proximal and distal colon cancers based on clinico- pathological, molecular and protein profiles. Int J Oncol 2010;37: 707-18.
    [25] Okoń K, Zazula M, Rudzki Z, Papla B, Osuch C, Stachura J. CDX-2 ex-pression is reduced in colorectal carcinomas with solid growth pattern and proximal location, but is largely independent of MSI status. Pol J Pathol 2004;55:9-14.
    [31] Byrd JC, Bresalier RS. Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev nd;23:77–99.
    [35] Kirsch R, Messenger DE, Riddell RH, et al. Venous invasion in colorectal cancer: impact of an elastin stain on detection and interob-server agreement among gastrointestinal and nongastrointestinal pathol-ogists. Am J Surg Pathol 2013;37:200-10. https://doi.org/10.1097/PAS. 0b013e31826a92cd.
    Contents lists available at ScienceDirect
    European Journal of Pharmacology
    journal homepage: www.elsevier.com/locate/ejphar r> Molecular and cellular pharmacology
    Celastrol strongly inhibits proliferation, migration and cancer stem cell T
    properties through suppression of Pin1 in ovarian cancer cells
    Xiaojing Lia, ,1, Hongmin Wanga,1, Jie Dingb, Shaozhen Niea, Li Wangc, Lili Zhangc, Shaoda Renb,d,
    a School of Pharmacy, Liaocheng University, Shandong 252000, PR China
    b Central Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong 252000, PR China
    c Department of Gynecology and Obstetrics, Liaocheng People's Hospital, Liaocheng, Shandong 252000, PR China
    d State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, PR China
    Keywords:
    Ovarian cancer
    Celastrol
    Cancer stem cell
    Ovarian cancer is one of the most serious diseases worldwide and the fifth-most common cancer among women. Celastrol, extracted from Thunder God Vine, exerts anti-cancer effects on various cancers; however, the me-chanism underlying these anti-cancer effects in ovarian cancer needs further investigation. Herein, we in-vestigated the anti-cancer efficacy of celastrol and its underlying mechanism in human ovarian cancer cell lines A2780, OVCAR3, and SKOV3. Celastrol significantly suppressed cell proliferation and migration in a dose-de-pendent manner. Celastrol resulted in a G2/M cell cycle arrest, accompanied with the down-regulation of Cyclin D1, CDK2, and CDK4. Celastrol induced apoptosis primarily via up-regulation of caspase-3, caspase-8, and Bax, and down-regulation of Bcl-2. Celastrol treatment inhibited the expression of stem cell marker CD44, Nanog, Klf4, and Oct4, and reduced a portion of the CD44highCD24low cell population. To further understand the cancer therapeutic target, we assessed the effect of celastrol on expression of Pin1, which is reportedly overexpressed in many human cancers and activates more than 40 oncogenes or inactivates more than 20 tumor suppressor genes. We report that celastrol particularly suppressed Pin1 expression, thereby inhibiting Akt, STAT3, P38, JNK, P65, and IL-6 expression. Taken together, these findings indicate that celastrol is a potential therapeutic agent for ovarian cancer in humans via inhibition of Pin1 expression.