Thyroid status as prognostic marker in oncology

2015 ◽  
Vol 6 (3) ◽  
pp. 112-117
Author(s):  
Ruslan Ivanovich Glushakov ◽  
Olga Valerievna Vlaseva ◽  
Ivan Viktorovich Sobolev ◽  
Sergei Nikolaevich Proshin ◽  
Natalya Igorevna Tapil’skaya
Keyword(s):  
Clinical Oncology ◽  
Malignant Tumors ◽  
Clinical Stage ◽  
Integrin Αvβ3 ◽  
Mitogen Activated Protein Kinase ◽  
Response To Treatment ◽  
Stage Of Disease ◽  
Nongenomic Action ◽  
Mitogen Activated Protein ◽  
Elevated Expression

In spite of advances in the treatment of malignant tumors of various localizations, in general, the survival rate for a variety of clinical entities remains unsatisfactory. There is no doubt that the predictive value of clinical stage of disease is very valuable. However in each particular case the correlation between the stage of disease and its outcome is rather probable than absolute. The current laboratory and pathological methods of risk assessment of course and recurrence of tumor in patients suffered from malignancies are not always sufficient, adequate and in most cases are able to ascertain a certain degree of risk without dosage adjustment possibilities. In the middle of the last century hypothyroidism was recognized as a risk factor for the development of certain malignancies, such as breast cancer, that has for several decades thesis conclusive clinical oncology. However at the turn of the century advances in molecular biology have called into question many of the existing dogma of experimental and clinical oncology. The review presents data about nongenomic properties of thyroid hormones (TH). Extracellular domains of integrin αVβ3, which is cell adhesion protein, are entrance for nongenomic way of TH. Binding of TH to αVβ3 results in activation of mitogen-activated protein kinase (fosfatidil-inositol-3-kinase). The finale effects of TH nongenomic action are cell proliferation, angiogenesis, migration of cells and elevated expression of tissue specific inflammatory genes. The clinical studies presented here trace pattern between increase in response to treatment and increase in survival of cancer patients with hypothyroid condition.

scholarly journals Elevated Expression of Mitogen-Activated Protein Kinase Phosphatase 3 in Breast Tumors: A Mechanism of Tamoxifen Resistance

2006 ◽  
Vol 66 (11) ◽  
pp. 5950-5959 ◽  
Author(s):  
Yukun Cui ◽  
Irma Parra ◽  
Mao Zhang ◽  
Susan G. Hilsenbeck ◽  
Anna Tsimelzon ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tamoxifen Resistance ◽  
Breast Tumors ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Elevated Expression

scholarly journals Correlation of P38 Mitogen-Activated Protein Kinase Expression to Clinical Stage in Nasopharyngeal Carcinoma

2018 ◽  
Vol 6 (11) ◽  
pp. 1982-1985 ◽  
Author(s):  
Farhat Farhat ◽  
Elvita Rahmi Daulay ◽  
Jessy Chrestella ◽  
Rizalina Arwinati Asnir ◽  
Ashri Yudhistira ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Kinase ◽  
Nasopharyngeal Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Stage ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Keratinizing Squamous Cell Carcinoma ◽  
Kinase Expression

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon and usually diagnosed at the advanced stage. A subfamily of mitogen-activated protein kinase which is called p38 mitogen-activated protein kinase (MAPK) involved in response to stress, and plays an important role in cell regulation. There is a suggestion that p38 mitogen-activated protein kinase could be a potential biomarker to determine the clinical stage of nasopharyngeal carcinoma. AIM: The aim of this study is for observing and analysing the correlation of p38 mitogen-activated protein kinase expression in regards to nasopharyngeal carcinoma patient’s clinical stage. METHODS: This study involved 126 nasopharyngeal carcinoma patients admitted to Haji Adam Malik General Hospital. RESULTS: The result of this study indicates that nasopharyngeal carcinoma mostly found in the age group 41-60 years, male, non-keratinizing squamous cell carcinoma, and stage IV group. In immunohistochemistry evaluation, most of p38 mitogen-activated protein kinase overexpressed in non-keratinizing squamous cell carcinoma, T3-T4, N2-N3 and clinical stage III-IV. Spearman’s test for categorical correlation yield p-value of < 0.001. CONCLUSION: In conclusion, there is a significant correlation between p38 mitogen-activated protein kinase expression and the clinical stage of nasopharyngeal carcinoma.

scholarly journals Dentine sialophosphoprotein signal in dentineogenesis and dentine regeneration

2021 ◽  
Vol 42 ◽  
pp. 43-62
Author(s):  
MM Liu ◽  
WT Li ◽  
XM Xia ◽  
F Wang ◽  
M MacDougall ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Dental Pulp ◽  
Integrin Αvβ3 ◽  
Cellular Membrane ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Rgd Motif ◽  
Mitogen Activated Protein ◽  
Rgd Site

Dentineogenesis starts on odontoblasts, which synthesise and secrete non-collagenous proteins (NCPs) and collagen. When dentine is injured, dental pulp progenitors/mesenchymal stem cells (MSCs) can migrate to the injured area, differentiate into odontoblasts and facilitate formation of reactionary dentine. Dental pulp progenitor cell/MSC differentiation is controlled at given niches. Among dental NCPs, dentine sialophosphoprotein (DSPP) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, whose members share common biochemical characteristics such as an Arg-Gly-Asp (RGD) motif. DSPP expression is cell- and tissue-specific and highly seen in odontoblasts and dentine. DSPP mutations cause hereditary dentine diseases. DSPP is catalysed into dentine glycoprotein (DGP)/sialoprotein (DSP) and phosphoprotein (DPP) by proteolysis. DSP is further processed towards active molecules. DPP contains an RGD motif and abundant Ser-Asp/Asp-Ser repeat regions. DPP-RGD motif binds to integrin αVβ3 and activates intracellular signalling via mitogen-activated protein kinase (MAPK) and focal adhesion kinase (FAK)-ERK pathways. Unlike other SIBLING proteins, DPP lacks the RGD motif in some species. However, DPP Ser-Asp/Asp-Ser repeat regions bind to calcium-phosphate deposits and promote hydroxyapatite crystal growth and mineralisation via calmodulin-dependent protein kinase II (CaMKII) cascades. DSP lacks the RGD site but contains signal peptides. The tripeptides of the signal domains interact with cargo receptors within the endoplasmic reticulum that facilitate transport of DSPP from the endoplasmic reticulum to the extracellular matrix. Furthermore, the middle- and COOH-terminal regions of DSP bind to cellular membrane receptors, integrin β6 and occludin, inducing cell differentiation. The present review may shed light on DSPP roles during odontogenesis.

scholarly journals NFB-05. AN UNUSUAL PRESENTATION OF RECURRENT LANGERHANS CELL HISTIOCYTOSIS OF THE CRANIOFACIAL BONES IN A PATIENT WITH NEUROFIBROMATOSIS TYPE I

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii418-iii418
Author(s):  
Blake Chaffee ◽  
Alexis Judd ◽  
Sarah Rush ◽  
Erin Wright
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Malignant Tumors ◽  
Neurofibromatosis Type ◽  
Mapk Signaling ◽  
Langerhans Cell ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Braf Mutations ◽  
Surveillance Imaging ◽  
Mitogen Activated Protein

Abstract Neurofibromatosis type 1 (NF1), predisposes patients to benign and malignant tumors due to lack of suppression of the mitogen activated protein kinase (MAPK) signaling pathway. Langerhans cell histiocytosis (LCH) manifests in numerous ways, from localized lesions to multisystem organ involvement secondary to a constitutively active MAPK signaling cascade often driven by BRAF mutations. While both LCH and NF1 are characterized by overactive MAPK signaling, there are few reports of the two diseases occurring simultaneously. We report a novel case of a patient with underlying NF1 and recurrent LCH without a BRAFV600E mutation. She initially presented at 2 years of age with an aggressive appearing mass of the left temporal bone found on surveillance imaging. Pathology was consistent with Langerhans histiocytosis and she was treated with the LCH-III protocol for patients with high-risk LCH due to the location of her lesion. Five years after completion of therapy, MRI demonstrated development of a calvarial mass consistent with relapsed LCH in a new risk site. Lesional curettage was performed and pathology confirmed recurrence of LCH with juvenile xanthogranulomatous features. BRAF testing of blood and the lesion were negative for any BRAF alterations. Further genomic evaluation of the tumor is in progress at this time to evaluate for other known mutations associated with LCH. The patient is currently receiving monthly cytarabine treatment which she has tolerated to date. Our patient represents a unique presentation of recurrent LCH in a patient with NF1 and further molecular evaluation may help identify other drivers of LCH activation.

scholarly journals Expression of tripartite motif‑containing 44 and its prognostic and clinicopathological value in human malignancies：a meta-analysis

2020 ◽  
Author(s):  
Guoliang Xiao ◽  
Qiuxi Yang ◽  
Ziwei Bao ◽  
Haixia Mao ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Meta Analysis ◽  
Clinical Stage ◽  
Mrna Level ◽  
Disease Free Survival ◽  
Expression Level ◽  
Advanced Clinical Stage ◽  
Normal Tissues ◽  
Tripartite Motif ◽  
Elevated Expression

Abstract Background: Previous researches have reported that tripartite motif-containing 44 (TRIM44) is related to the prognosis of multiple human tumors. This study was designed to systematically assess the prognostic value of TRIM44 in human malignancies and summarize its possible tumor-related mechanisms.Methods: The available databases were searched for eligible studies that evaluated the clinicopathological and prognostic roles of TRIM44 in patients with malignancies. The hazard ratios (HR) and odds ratios (OR) were combined to assess the predictive role of TRIM44 using Stata/SE 14.1 software.Results: A total of 1,740 patients from thirteen original studies were finally included in this study. The results of the combined analysis showed that over-expression of TRIM44 protein was significantly correlated with shorter overall survival (OS) (HR = 1.94, 95% CI: 1.60-2.35) and worse disease-free survival (DFS) (HR= 2.13, 95% CI: 1.24-3.65) in cancer patients. Additionally, the combined ORs indicated that elevated expression level of TRIM44 protein was significantly associated with lymph node metastasis (OR=2.69, 95% CI: 1.71-4.24), distant metastasis (OR=10.35, 95% CI: 1.01-106.24), poor tumor differentiation (OR=1.78, 95% CI: 1.03-3.09), increased depth of tumor invasion (OR=2.72, 95% CI: 1.73-4.30), advanced clinical stage (OR=2.75, 95% CI: 2.04-3.71), and recurrence (OR=2.30, 95% CI: 1.34-3.95). Furthermore, analysis results using Gene Expression Profiling Interactive Analysis (GEPIA) showed that the expression level of TRIM44 mRNA was higher in most tumor tissues than in the corresponding normal tissues, and the relationship between TRIM44 mRNA level and prognosis in various malignant tumors also explored in GEPIA and OS analysis webservers.Conclusions: TRIM44 may serve as a valuable prognostic biomarker and a potential therapeutic target for patients with malignancies.

scholarly journals Thyroid diseases and risk of non-thyroidal pathology

2017 ◽  
Vol 98 (1) ◽  
pp. 77-84 ◽  
Author(s):  
R I Glushakov ◽  
E V Kozyrko ◽  
I V Sobolev ◽  
S A Ermolova ◽  
O V Vlaseva ◽  
...  
Keyword(s):  
Integrin Αvβ3 ◽  
Epidemiological Data ◽  
Epidemiological Studies ◽  
Population Based ◽  
Thyroid Diseases ◽  
Tissue Response ◽  
Mitogen Activated Protein Kinase ◽  
Malignant Neoplasms ◽  
Thyroid Pathology ◽  
Mitogen Activated Protein

The review presents generalized epidemiological data on the prevalence of non-neoplastic thyroid pathology in developed and developing countries, in particular in regions with iodine deficiency and the influence of mass iodine prophylaxis on reducing the incidence and prevalence of thyroid diseases in these regions. The data on the prevalence of subclinical hypo- and hyperthyroidism are presented, where according to the averaged data 1 clinical manifestation of thyroid insufficiency accounted for 20 cases of unregistered subclinical hypothyroidism, and 1 case of identified thyroid hyperfunction accounted for 15 cases of subclinical hyperthyroidism. Methodological, clinical and social difficulties in studying the prevalence of thyroid pathology are described. The main nongenomic actions of thyroid hormones, which originated from extracellular domains of cell adhesion protein - integrin αVβ3, resulting in activation of mitogen-activated protein kinase, phosphatidylinositol-3 kinase and serine-threonine-protein kinases, are presented. The ultimate cell and tissue response to this stimulation is the activation of cell proliferation, angiogenesis, cell migration, and increased expression of tissue-specific proinflammatory genes, which ultimately lead to acceleration of the «cancer development and its natural history». Data from epidemiological studies, which established a correlation between thyroid status and incidence (prevalence) of malignant neoplasms, are given. As a result of population-based studies analysis it was demonstrated that long term hyperthyroidism increases the risk of developing malignant neoplasms of different localizations, in particular breast, ovarian, prostate and lung cancer.

scholarly journals Akt Phosphorylation Is Not Sufficient for Insulin-Like Growth Factor-Stimulated Myogenin Expression but Must Be Accompanied by Down-Regulation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Phosphorylation

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4991-4996 ◽  
Author(s):  
Nicki Tiffin ◽  
Saleh Adi ◽  
David Stokoe ◽  
Nan-Yan Wu ◽  
Stephen M. Rosenthal
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Myogenic Differentiation ◽  
Mitogen Activated Protein Kinase ◽  
Response To Treatment ◽  
Akt Phosphorylation ◽  
Extracellular Signal ◽  
Phosphorylated Akt ◽  
Igf I ◽  
Mitogen Activated Protein

Abstract IGF-I has a unique biphasic effect on skeletal muscle differentiation. Initially, IGF-I inhibits expression of myogenin, a skeletal muscle-specific regulatory factor essential for myogenesis. Subsequently, IGF-I switches to stimulating expression of myogenin. The mechanisms that mediate this switch in IGF action are incompletely understood. Several laboratories have demonstrated that the phosphatidylinositol-3-kinase/Akt signaling pathway is essential for myogenic differentiation and have suggested that this pathway mediates IGF-I stimulation of myogenin mRNA expression, an early critical step in the differentiation process. These studies, however, did not address concurrent Akt and MAPK/ERK1/2 phosphorylation, the latter of which is also known to regulate myogenic differentiation. In the present study in rat L6E9 muscle cells, we have manipulated ERK1/2 phosphorylation with either an upstream inhibitor or activator and examined concurrent levels of Akt and ERK1/2 phosphorylation and of myogenin mRNA expression in response to treatment with IGF-I. We find that even in the presence of phosphorylated Akt, it is only when ERK1/2 phosphorylation is inhibited that IGF-I can stimulate myogenin mRNA expression. Thus, although Akt phosphorylation may be necessary, it is not sufficient for induction of myogenic differentiation by IGF-I and must be accompanied by a decrease in ERK1/2 phosphorylation.

scholarly journals JAMP, a Jun N-Terminal Kinase 1 (JNK1)-Associated Membrane Protein, Regulates Duration of JNK Activity

2005 ◽  
Vol 25 (19) ◽  
pp. 8619-8630 ◽  
Author(s):  
Takayuki Kadoya ◽  
Ashwani Khurana ◽  
Marianna Tcherpakov ◽  
Kenneth D. Bromberg ◽  
Christine Didier ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Mitogen Activated Protein Kinase ◽  
Treatment Results ◽  
Apoptosis Inhibition ◽  
Mitogen Activated Protein ◽  
Elevated Expression ◽  
Induced Apoptosis ◽  
Jnk Activation ◽  
Identification And Characterization

ABSTRACT We report the identification and characterization of JAMP (JNK1 [Jun N-terminal kinase 1]-associated membrane protein), a predicted seven-transmembrane protein that is localized primarily within the plasma membrane and associates with JNK1 through its C-terminal domain. JAMP association with JNK1 outcompetes JNK1 association with mitogen-activated protein kinase phosphatase 5, resulting in increased and prolonged JNK1 activity following stress. Elevated expression of JAMP following UV or tunicamycin treatment results in sustained JNK activity and a higher level of JNK-dependent apoptosis. Inhibition of JAMP expression by RNA interference reduces the degree and duration of JNK activation and concomitantly the level of stress-induced apoptosis. Through its regulation of JNK1 activity, JAMP emerges as a membrane-anchored regulator of the duration of JNK1 activity in response to diverse stress stimuli.

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