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Peter Dietrich, Silke Kuphal, Thilo Spruss, Claus Hellerbrand, Anja K Bosserhoff
The network of molecular players is similar when comparing neural crest-derived, actively migrating melanoblasts to melanoma cells. However, melanoblasts are sensitive to differentiation-initiating signals at their target site (epidermis), while melanoma cells maintain migratory and undifferentiated features. We aimed at identifying downregulated genes in melanoma that are particularly upregulated in melanoblasts. Loss of such genes could contribute to stabilization of a dedifferentiated, malignant phenotype in melanoma...
March 1, 2018: Pigment Cell & Melanoma Research
Zsuzsanna Gaál, Éva Oláh, László Rejtő, Bálint László Bálint, László Csernoch
Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124...
January 2017: Pathology Oncology Research: POR
Zsuzsanna Gaál, Éva Oláh, László Rejtő, Ferenc Erdődi, László Csernoch
Histone deacetylase enzymes, confirmed to have important role in the pathogenesis of leukemia, are promising targets of epigenetic treatment. However, in acute myeloid leukemia, our knowledge on their expression levels is limited, and controversial data have been published about their potential oncogenic or tumorsuppressor properties in solid tumors. In our study, the expression levels of HDAC4 and SIRT6 were evaluated via Western blot analysis in 45 bone marrow samples (2 uninfiltrated and 43 concerned by different kinds of hematological malignancies), including 32 specimens obtained from patients with newly diagnosed AML...
July 2017: Pathology Oncology Research: POR
Zhengzhi Zhu, Shengying Wang, Jinhai Zhu, Qifeng Yang, Huiming Dong, Jiankang Huang
Triple negative breast cancer lacking estrogen receptor (ER), progesterone receptor and Her2 account for account for the majority of the breast cancer deaths, due to the lack of specific gene targeted therapy. Our current study aimed to investigate the role of miR-544 in triple negative breast cancer. Endogenous levels of miR-544 were significantly lower in breast cancer cell lines than in human breast non-tumorigenic and mammary epithelial cell lines. We found that miR-544 directly targeted the 3'-untranslated region (UTR) on both Bcl6 and Stat3 mRNAs, and overexpression of miR-544 in triple negative breast cancer cells significantly down-regulated expressions of Bcl6 and Stat3, which in turn severely inhibited cancer cell proliferation, migration and invasion in vitro...
October 1, 2016: Biological Chemistry
Alexander I Damanakis, Sabine Eckhardt, Annette Wunderlich, Silvia Roth, Thaddeus T Wissniowski, Detlef K Bartsch, Pietro Di Fazio
PURPOSE: Thyroid cancer (TC), the most common endocrine malignancy, increases its incidence worldwide. MicroRNAs have been shown to be abnormally expressed in tumors and could represent valid diagnostic markers for patients affected by TC. Our aim was to analyze the expression of tumorsuppressor hsa-let7b-5p and hsa-let7f-5p, together with their predicted targets SLC5A5 (NIS) and HMGA2, in papillary (PTC), follicular (FTC) and anaplastic (ATC). METHODS: 8 FTC, 14 PTC, 12 ATC and three normal thyroid tissue samples were analyzed for the expression of pre-let7b, hsa-let7b-5p and hsa-let7f-5p as SLC5A5 and HMGA2 by RT-qPCR...
June 2016: Journal of Cancer Research and Clinical Oncology
Carina Fischer, Susanne Scheipl, Agnes Zopf, Norbert Niklas, Alexander Deutsch, Mette Jorgensen, Birgit Lohberger, Elke Verena Froehlich, Andreas Leithner, Christian Gabriel, Bernadette Liegl-Atzwanger, Beate Rinner
BACKGROUND: Chordoma is a rare primary malignant bone tumour. Treatment options are mainly restricted to surgical excision, since chordomas are largely resistant to conventional ionising radiation and chemotherapy. Thus, there is a strong need to gain more thorough insights into the molecular biology and genetics of chordoma to allow for the development of new therapeutic options. We performed an ultra-deep sequencing analysis to find novel mutations in cancer associated genes in chordomas to date unseen with Sanger sequencing...
2015: Journal of Cancer
Rajesh Thangapazham, Francisco Saenz, Shilpa Katta, Ahmed A Mohamed, Shyh-Han Tan, Gyorgy Petrovics, Shiv Srivastava, Albert Dobi
BACKGROUND: In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context...
January 13, 2014: BMC Cancer
Masanao Nakamura, Yoshiki Hirooka, Takeshi Yamamura, Koji Yamada, Asuka Nagura, Toru Yoshimura, Naoki Ohmiya, Keisuke Uehara, Yuichiro Yoshioka, Masato Nagino, Hidemi Goto
To our knowledge, this is the first report of Cowden syndrome complicated by a gastrointestinal stromal tumor (GIST) of the small bowel. A 42-year-old female patient was found to have an abdominal mass that was diagnosed as the cause of anemia and was surgically extracted. The surgical specimen was found to be a GIST. During the same period, the patient underwent an endoscopic examination of the entire gastrointestinal tract. She was also diagnosed as having Cowden syndrome based on gastrointestinal polyps and skin, thyroid and breast lesions...
September 2014: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
Jörg Fahrer, Johannes Rausch, Holger Barth
Genetically engineered bacterial protein toxins are attractive systems for delivery of exogenous proteins into the cytosol of mammalian cells. The binary C2 toxin from C. botulinum has emerged as powerful delivery vehicle, which rests on its binding/translocation component C2IIa and the genetically modified adaptor domain C2IN that act in concert to trigger cell uptake. The p53 tumor suppressor protein has a crucial function in suppressing carcinogenesis and is frequently inactivated by diverse mechanisms in human tumor cells...
2013: PloS One
The cells of the malignant clone of plasmacell myeloma have cytogenetic aberrations in a substantial number of cases. Many of these abnormal karyotypes are predictive for an unfavorable outcome. Gene mutations and abnormal gene expression, particularly of oncogenes and tumorsuppressor genes, are often observed in myeloma cells. The cross talk between the myeloma cells and the bone marrow microenvironment plays an important role for growth and survival of the tumor cells. As a consequence of this cell-to-cell-interaction, several cytokines are secreted...
April 1, 2006: Therapeutische Umschau. Revue Thérapeutique
Hung-Wei Pan, Sung-Chou Li, Kuo-Wang Tsai
Gastric carcinogenesis is a complex multistep process involving genetic dysregulation of proto-oncogenes and tumorsuppressor genes, and has recently entered the era of microRNAs (miRNAs), a class of small non-coding RNAs that posttranscriptionally regulate gene expression and control various cellular functions. MicroRNAs are small (approximately 22 nucleotides) non-coding RNAs that play fundamental roles in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis, and carcinogenesis...
2013: Current Pharmaceutical Design
Mir Farshid Alemdehy, Stefan J Erkeland
MicroRNAs (miRNAs) belong to an abundant class of highly conserved small (22nt) non-coding RNAs. MiRNA profiling studies indicate that their expression is highly cell type-dependent. DICER1 is an essential RNase III endoribonuclease for miRNA processing. Hematopoietic cell type- and developmental stage-specific Dicer1 deletion models show that miRNAs are essential regulators of cellular survival, differentiation and function. For instance, miRNA deficiency in hematopoietic stem cells and progenitors of different origins results in decreased cell survival, dramatic developmental aberrations or dysfunctions in mice...
August 1, 2012: Cell Cycle
Pietro Di Fazio, Roberta Montalbano, Daniel Neureiter, Beate Alinger, Ansgar Schmidt, Anna Lena Merkel, Karl Quint, Matthias Ocker
Inhibitors of protein deacetylases represent a novel therapeutic option for cancer diseases due to their effects on transcriptional regulation by interfering with histones acetylation and on several other cellular pathways. Recently, their ability to modulate several transcription factors and, interestingly, also co-factors, which actively participate in formation and modulation of transcription complexes was shown. We here investigate whether HMGA2 (High Mobility Group AT-2 hook), a nuclear non-histone transcriptional co-factor with known oncogenic properties, can be influenced by the novel pan-deacetylase inhibitor panobinostat (LBH589) in human hepatocellular carcinoma models...
September 10, 2012: Experimental Cell Research
Margherita Gigante, Loreto Gesualdo, Elena Ranieri
The capacity of the immune system to distinguish foreign from self-antigen, and to subsequently eliminate the threat of disease without injuring the host is crucial for survival. It also serves to defend against tumor formation and progression via a process termed cancer immunosurveillance. Innate and adaptive immune cell types and effector molecules collectively function as extrinsic tumorsuppressor mechanisms. However, tumors may escape immunesurveillance through a variety of mechanisms that create a local microenvironment that is unfavorable for effective tumor immunity...
2012: Current Pharmaceutical Design
Gerben Duns, Robert M W Hofstra, Jantine G Sietzema, Harry Hollema, Inge van Duivenbode, Angela Kuik, Cor Giezen, Osinga Jan, Jelkje J Bergsma, Harrie Bijnen, Pieter van der Vlies, Eva van den Berg, Klaas Kok
Clear cell renal cell carcinomas are characterized by 3p loss, and by inactivation of Von Hippel Lindau (VHL), a tumorsuppressor gene located at 3p25. Recently, SETD2, located at 3p21, was identified as a new candidate ccRCC tumor-suppressor gene. The combined mutational frequency in ccRCC tumors of VHL and SETD2 suggests that there are still undiscovered tumor-suppressor genes on 3p. We screened all genes on 3p for mutations in 10 primary ccRCC tumors using exome-sequencing. We identified inactivating mutations in VHL, PBRM1, and BAP1...
July 2012: Human Mutation
Christian R Loehberg, Pamela L Strissel, Ralf Dittrich, Reiner Strick, Juergen Dittmer, Angela Dittmer, Ben Fabry, Willi A Kalender, Thorsten Koch, David L Wachter, Nicole Groh, Astrid Polier, Ina Brandt, Laura Lotz, Inge Hoffmann, Florentine Koppitz, Sonja Oeser, Andreas Mueller, Peter A Fasching, Michael P Lux, Matthias W Beckmann, Michael G Schrauder
PI3K/Akt/mTOR and p53 signaling pathways are frequently deregulated in tumors. The anticancer drug RAD001 (everolimus) is a known mTOR-inhibitor, but mTOR-inhibition leads to phosphorylation of Akt inducing resistance against RAD001 treatment. There is growing evidence that conflicting signals transduced by the oncogene Akt and the tumorsuppressor p53 are integrated via negative feedback between the two pathways. We previously showed that the anti-malarial Chloroquine, a 4-alkylamino substituted quinoline, is a p53 activator and reduced the incidence of breast tumors in animal models...
February 15, 2012: Biochemical Pharmacology
Nehad M R Abd El-Maqsoud, Ehab Rifat Tawfiek
BACKGROUND AND PURPOSE: Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily of protease inhibitors and is known to have tumorsuppressor function in breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of Maspin in squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of urinary bladder. PATIENTS AND METHODS: We have evaluated the immunohistochemical expression of Maspin and p53 in a series of 134 bladder cancer patients (56 SCC and 78 TCC) and the interrelationship between clinicopathological features and Maspin and p53 expression...
March 2010: Journal of the Egyptian National Cancer Institute
P S Obermiller, J T Holt
The human breast and ovarian cancer susceptibility gene BRCA1 is a tumorsuppressor gene which is mutated and lost in hereditary breast and ovarian cancer, and has both alleles mutated in approximately 10-15% of cases of sporadic ovarian cancer. Studies of chromosome loss in ovarian cancer show that at least one allele of the BRCA1 gene is lost or mutated in up to 70% of sporadic ovarian cancers. Although no sporadic breast cancers contain BRCA1 mutations, our published study shows that expression of the mRNA is decreased suggesting that the BRCA1 gene is altered quantitatively in sporadic cancer and qualitatively in hereditary cancer...
2000: Methods in Molecular Medicine
J A Macoska
Allelic loss of human chromosome sequences contributes to tumorigenesis through the inactivation of putative tumor-suppressor genes. The Knudson hypothesis proposes that deletion or mutation must affect both alleles of the gene in order to disable tumor suppression (1). As might be expected, the effect of "two hits" on tumor-suppressor gene integrity-e.g., deletion of one allele and mutation of the remaining allele-would disable the gene from encoding gene product. The von Hippel-Lindau (VHL) gene is an example of a tumorsuppressor gene that fulfills the Knudson hypothesis-e...
2001: Methods in Molecular Medicine
Christopher Ungerer, Kai Doberstein, Claudia Bürger, Katja Hardt, Wolf-Henning Boehncke, Beate Böhm, Josef Pfeilschifter, Reinhard Dummer, Daniela Mihic-Probst, Paul Gutwein
In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma...
October 22, 2010: Biochemical and Biophysical Research Communications
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