Findings from the Peutz-Jeghers syndrome registry of Uruguay
Name:
Article-PLoS_ONE-Findings_f-2013.pdf
Size:
1.642Mb
Format:
PDF
Description:
Article - Full Text
Type
ArticleAuthors
Tchekmedyian, AsadurAmos, Christopher I.
Bale, Sherri J.
Zhu, Dakai
Arold, Stefan T.
Berrueta, Joaquin
Nabon, Natalie
McGarrity, Thomas
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Structural Biology and Engineering
Date
2013-11-19Permanent link to this record
http://hdl.handle.net/10754/325328Metadata
Show full item recordAbstract
Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000. Conclusion: The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation. © 2013 Tchekmedyian et al.Citation
Tchekmedyian A, Amos CI, Bale SJ, Zhu D, Arold S, et al. (2013) Findings from the Peutz-Jeghers Syndrome Registry of Uruguay. PLoS ONE 8: e79639. doi:10.1371/journal.pone.0079639.Publisher
Public Library of Science (PLoS)Journal
PLoS ONEPubMed ID
24260271PubMed Central ID
PMC3834183Scopus Count
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Related items
Showing items related by title, author, creator and subject.
-
Cytotoxicity and apoptosis induced by a plumbagin derivative in estrogen positive MCF-7 breast cancer cells(Anti-Cancer Agents in Medicinal Chemistry, Bentham Science Publishers Ltd., 2014-01-14) [Article]Plumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anticancer lead compound. Several efforts have been made to synthesize its analogs and derivatives in order to increase its anticancer potential. In the present study, plumbagin and its five derivatives have been evaluated for their antiproliferative potential in one normal and four human cancer cell lines. Treatment with derivatives resulted in dose- and time-dependent inhibition of growth of various cancer cell lines. Prescreening of compounds led us to focus our further investigations on acetyl plumbagin, which showed remarkably low toxicity towards normal BJ cells and HepG2 cells. The mechanisms of apoptosis induction were determined by APOPercentage staining, caspase-3/7 activation, reactive oxygen species production and cell cycle analysis. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7) was also measured using real time PCR. The positive staining using APOPercentage dye, increased caspase-3/7 activity, increased ROS production and enhanced mRNA expression of proapoptotic genes suggested that acetyl plumbagin exhibits anticancer effects on MCF-7 cells through its apoptosis-inducing property. A key highlighting point of the study is low toxicity of acetyl plumbagin towards normal BJ cells and negligible hepatotoxicity (data based on HepG2 cell line). Overall results showed that acetyl plumbagin with reduced toxicity might have the potential to be a new lead molecule for testing against estrogen positive breast cancer. 2014 Bentham Science Publishers.
-
A mechanically-induced colon cancer cell population shows increased metastatic potential(Molecular Cancer, Springer Nature, 2014-05-29) [Article]Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher's exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular, phenotypical, and mechanical signatures between the two cell types. To our knowledge, this is the first study that explores the molecular mechanism of E-R transition, which may greatly increase our understanding of the mechanisms of cancer mechanical microenvironment and initiation of cancer metastasis. 2014 Tang et al.; licensee BioMed Central Ltd.
-
Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment(Marine Drugs, MDPI AG, 2011-09-20) [Article]Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review. 2011 by the authors.
