China
Africa
Explore chapters and articles related to this topic
Differential Genetic Diagnosis between Leiomyoma and Leiomyosarcoma
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Alba Machado-Lopez, Aymara Mas
At the molecular level, myometrial tumors show unbalanced karyotypes as well as non-specific and complex alterations, such as SNVs, small indels, amplifications, and gene fusions (36,37). Specifically, up to 50% of LM have cytogenetic abnormalities, mainly affecting 6p21, 7q, and 12q15 chromosome regions as the main drivers, whereas point mutations in gene MED12 are detected in up to 70% of tumors (38). Chromosomal rearrangements between HMGA1/HMGA2 and RAD51B, or between COL4A5 and COL4A6 are also frequent in LM, mainly resulting in overexpression of these genes or reduced expression of CUX1 or CUL1 due to 7q deletions (25). Furthermore, heterozygous mutations in the FH (fumarate hydratase) gene can cause Reed's syndrome, also known as hereditary leiomyomatosis, and renal cell cancer syndrome, which is characterized by multiple cutaneous and uterine leiomyomas (Figure 25.3).
Insulin Resistance and Glucose Regulation
Published in Awanish Kumar, Ashwini Kumar, Diabetes, 2020
Reduction in IR expression has further been stated in obese mice models with hepatic steatosis. Further, it has been found that saturated fatty acids reduce the mRNA and protein level of IR in cell lines of hepatocyte and skeletal muscle. Some reports also suggest that IR expression is inversely related to protein kinase C (PKCε isoform) in obese animal models. PKCε has been found to impair the HMGA1 which is the major transcription factor of the IR gene. In a breakthrough study, it was reported that lipids phosphorylate PKCε through palmitoylation. Phosphorylated PKCε in turn impairs HMGA1 which finally reduces the IR expression leading to a significant decrease in insulin sensitivity [17].
Familial Testicular Germ Cell Tumor
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Immunohistochemical markers for TGCT consist of PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C), LIN28, etc., which are expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells. Other diagnostic markers include HMGA1, HMGA2, kinase Aurora-B (which is present in IGCNU, seminomas, and embryonal carcinomas but not in teratomas and YST) [50,51].
Targeting the intrinsically disordered architectural High Mobility Group A (HMGA) oncoproteins in breast cancer: learning from the past to design future strategies
Published in Expert Opinion on Therapeutic Targets, 2020
Silvia Pegoraro, Gloria Ros, Michela Sgubin, Sara Petrosino, Alberto Zambelli, Riccardo Sgarra, Guidalberto Manfioletti
High mobility group A (HMGA) proteins are non-histone nuclear proteins involved in gene expression regulation during embryogenesis and neoplastic transformation, where they are highly expressed, although they are almost undetectable in most adult tissues [reviewed within [1–4]]. This family includes two paralogous functional members: the HMGA1 and the HMGA2 genes that encode the HMGA1a and HMGA1b proteins, produced through alternative splicing, and the highly related HMGA2 protein, respectively [5]. These proteins are characterized by three highly conserved palindromic motifs (Pro-Arg-Gly-Arg-Pro), defined as ‘AT-hooks’, that bind to the minor groove of A/T rich B-form DNA sequences and an acidic C-terminal tail involved in the modulation of HMGA protein activities [reviewed within [1,3,6]]. Although these factors have no transcriptional activity per se, they contribute to gene expression regulation as chromatin architectural factors, altering the general chromatin status, competing with histone H1, interacting with transcription factors (TFs), and the transcription machinery [reviewed within [4]]. HMGA proteins bind to DNA and TFs, leading to the formation of stereospecific macromolecular complexes called ‘enhanceosomes’, which are crucial in transcription activation [7]. In addition to the role of HMGA proteins in gene transcription regulation, their involvement in other molecular processes, such as DNA repair [reviewed within [8]], DNA replication [9,10], chromatin structure [8,11], and RNA processing [12], is well established.
Effect of Doxorubicin on Squamous Cell Carcinoma of Skin: Assessment by MRI Relaxometry at 4.7T
Published in Cancer Investigation, 2019
Ashok Sharma, Uma Sharma, N. R. Jagannathan, Ruma Ray, Moganty Raja Rajeswari
Skin cancer is the most common form of cancer and its incidence is increasing world-wide. Non-melanoma skin cancer (NMSC) is the most common skin cancer which comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). About 80% of all NMSC are BCC while SCC of skin is the second most prevalent non-melanoma skin cancer which represents about 20%. The World Health Organization (WHO) estimates 4.3 million case of BCC and 1 million case of SCC in the United States each year, resulting in more than 3000 and 15,000 deaths respectively (http://www.skincancer.org) (1,2). SCC is an uncontrolled growth of abnormal cells arising from the squamous cells in the epidermis which is the outermost layer of skin (3). Most SCCs are treated surgically, but surgical treatment is not appropriate because higher risk for developing the clinically aggressive SCC and recurrence (4). SCC can be responsive to various chemotherapeutic agents; however no standard regimen of metastatic disease has been formulated yet, resulting in recurrences and/or metastasis (5). Combinations of cisplatin with 5-fluorouracil (5-FU), bleomycin or doxorubicin have demonstrated some degree of efficacy (6). Doxorubicin, an anthracycline antibiotic has been the choice of anticancer therapeutic due to its broad spectrum of applications starting from hematopoietic malignancy to non-Hodgkin lymphomas to solid tumors (7). Doxorubicin provokes reactive oxygen species (ROS) that can damage cellular components, proteins, lipids, DNA etc.; causing cell damage and inducing apoptosis (7,8). We have reported that HMGA1 expression is regulated by doxorubicin via interaction with a promoter region (9). High Mobility Group protein A1 (HMGA1), a non-histone protein, acts as an architectural transcription factor and is responsible for cell cycle transition, cell motility, migration, and invasion (9,10). HMGA1 protein is highly expressed in number of cancers like colorectal, prostate, liver, breast and skin cancer etc. HMGA1 enhances the cellular reprograming from a somatic cell to a fully pluripotent stem cell by activating the transcriptional networks (11). Due to their role in neoplastic transformation and tumor progression, HMGA1 protein is considered as a tumor marker and could be exploited as novel therapeutic and useful prognostic marker for cancers (12,13). These days molecular imaging is rapidly gaining recognition as a tool with capacity to understand the molecular and cellular processes and thus helping in treatment response assessment, restaging after treatment and the prognosis of many cancers in every aspect of cancer care (14).