Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The difficult cancer development and the insufficient knowledge of the biology of the existing cancers lead for the constant search for the new techniques of diagnosis. The aim of this study was to analyze the selected prognostic factors such as p53, Ki67 and cyclin D1 in patients with head and neck cancer in connection with histological differentiation (G), TNM classification and the clinical advancement of the disease (S). The material comprised of the tissue specimens from 32 patients with squamous cell carcinomas of head and neck, who underwent the primary surgery. The immunohistochemical study was performed with avidin-biothin method. A 5-point grading system was adopted to assess the level of the immunohistochemical staining of the carcinoma cells. Through our study we found a statistically significant correlation between the staining intensity of carcinoma cells for p53, Ki67, cyclin D1 and the TNM classification and the clinical advancement of the disease (S). Such correlation for the histological differentiation (G) has not been observed. We think that the immunohistochemical techniques may constitute an important supplement of evaluation of the malignancy in the squamous cell carcinomas of head and neck.
Otolaryngol Pol 2004
PMID:[Ki67, p53 and cyclin D1 in the squamous cell carcinoma of head and neck]. 1560 89

We report a case of a simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of a papillary carcinoma to the cervical lymph nodes and a concurrent small B-cell lymphocytic lymphoma revealed in the lymph nodes examined in a 71-year-old woman. The diagnosis was based on microscopic examination of surgical specimens and supported by immunohistochemistry. Additionally, P53 and RET mutation analysis was performed. In this case, the coincidence of medullary and papillary carcinomas of the thyroid gland may account for a true composite tumor. The coexistence of a small B-cell lymphoma in our patient may be explained by irradiation treatment undergone during the adolescence.
Pol J Pathol 2004
PMID:Simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of papillary carcinoma to the cervical lymph nodes and the coinciding small B-cell lymphocytic lymphoma of the lymph nodes--a case report. 1561 77

A case of malignant tumor developing from myoepithelial cells (malignant myoepithelioma) is presented. The primary focus was located in the region of the left submandibular salivary gland. A relapse and metastases were disclosed in the same salivary gland, in the lung and the left breast. Immunohistochemical studies demonstrated positive reactions for S-100 protein, cytokeratins, smooth muscle actin, vimentin, GFAP protein, p53 protein and Ki-67 antigen, and allowed for establishing the final histopathological diagnosis of malignant myoepithelioma.
Pol J Pathol 2004
PMID:Malignant myoepithelioma of the salivary gland--an untypical clinical course. 1561 79

The expression of P53 and P21WAF1 proteins was analyzed immunohistochemically in archival material derived from 12 cases of follicular thyroid carcinoma, 57 cases of follicular adenoma and 17 cases of nodular goiter. In the follicular carcinoma group 6 out of 12 cases (50%) were positive for P53 protein and 4 out of 12 cases (33.3%) were positive for P21WAF1 protein. In the follicular adenoma group, 18 out of 57 cases (31.6%) were positive for P53 and 16 out of 57 cases (28.1%) were positive for P21WAF1 protein. No positive cases of P53 or P21WAF1 proteins presence were found in the nodular goiter group. Positive correlation between the expression of P53 and P21WAF1 proteins was found for follicular carcinoma and adenoma groups (p = 0.034 and p = 0.002, respectively). The obtained results demonstrate that simultaneous immunohistochemical detection of P53 and P21WAF1 proteins expression may be useful in determining functional status of P53 protein, helping to interpret expression of P53 protein in thyroid follicular carcinoma cells.
Pol J Pathol 2004
PMID:Analysis of P53 and P21WAF1 proteins expression in follicular thyroid tumors. 1575

The p53 tumor suppressor plays the role of a cellular hub which gathers stress signals such as damage to DNA or hypoxia and translates them into a complex response. p53 exerts its action mainly as a potent transcription factor. The two major outcomes of p53 activity are highlighted: cell cycle arrest and apoptosis. During malignant transformation p53 or p53-pathway related molecules are disabled extremely often. Mutations in p53 gene are present in every second human tumor. A mutant form of p53 may not only negate the wild type p53 function but may play additional role in tumor progression. Therefore p53 represents a relatively unique and specific target for anticancer drug design. Current approaches include several different molecules able to restore p53 wild-type conformation and activity. Such small molecule drugs hold great promise in treating human tumors with dysfunction of p53 pathway in the near future.
Acta Biochim Pol 2005
PMID:Prospects for p53-based cancer therapy. 1599 Sep 17

Apoptosis is a physiological programmed cell death. The molecular regulation of this process is very complex and still unknown. Disregulation in the mechanisms controlling apoptosis are thought to be the cause of many diseases. Mutations in gene p53 lead to carcinous transformation, high expression of receptor Fas increases the cell elimination in chronic inflammatory processes. Wrong balance between apoptosis regulatory proteins Bcl-2/Bax is the reason for low mortality, radioresistance and chemoresistance. Studies of mechanisms controlling interactions between apoptotic proteins will let us find new diagnostic and therapeutic methods.
Pol Merkur Lekarski 2005 Mar
PMID:[Apoptosis--molecular basis in pathogenesis of selected chronic inflammatory and neoplastic diseases]. 1599 45

Vulvar carcinoma accounts for 3-5% of all genital cancers. The most common histology of vulvar cancer is squamous cell carcinoma. It has been suggested that vulvar cancer exists as two separate diseases--HPV-positive, occurring in young women, and p53-positive, that occurs in older women. As extensive surgery resection is gold standard of treatment, it is important to play attention for all symptoms, suggesting the beginning of disease. Understanding of the anatomy and the mechanism of lymphatic spread have made modifications in surgical technique possible, allowing less radical excisions.
Pol Merkur Lekarski 2005 Mar
PMID:[Can vulvar carcinoma be a danger in the 21st century?]. 1599 47

PTEN is a tumor suppressor whose function is frequently lost in human cancer. It possesses a lipid phosphatase activity that represses the activation of PI3 kinase/Akt signaling, leading to decreased cell growth, proliferation, and survival. The potential for PTEN to regulate transcription of the large rRNAs by RNA polymerase I (RNA Pol I) was investigated. As increased synthesis of rRNAs is a hallmark of neoplastic transformation, the ability of PTEN to control the transcription of rRNAs might be crucial for its tumor suppressor function. The expression of PTEN in PTEN-deficient cells represses RNA Pol I transcription, while decreasing PTEN expression enhances transcription. PTEN-mediated repression requires its lipid phosphatase activity and is independent of the p53 status of the cell. This event can be uncoupled from PTEN's ability to regulate the cell cycle. RNA Pol I is regulated through PI3 kinase/Akt/mammalian target of rapamycin/S6 kinase, and the expression of constitutively activated S6 kinase is able to abrogate transcription repression by PTEN. No change in the expression of the RNA Pol I transcription components, upstream binding factor or SL1, was observed upon PTEN expression. However, chromatin immunoprecipitation assays demonstrate that PTEN differentially reduces the occupancy of the SL1 subunits on the rRNA gene promoter. Furthermore, PTEN induces dissociation of the SL1 subunits. Together, these results demonstrate that PTEN represses RNA Pol I transcription through a novel mechanism that involves disruption of the SL1 complex.
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PMID:PTEN represses RNA Polymerase I transcription by disrupting the SL1 complex. 1605 4

We recently observed an interaction between poly(ADP-ribose) polymerase-1 (PARP-1) and the tumor suppressor p53 protein. However, more extensive studies on both proteins, especially those on characterization of their domains involved in the interaction were difficult due to very low expression levels of p53 in mammalian cells. Therefore, we generated recombinant proteins for such studies. To clarify which domains of human PARP-1 and of human wild-type (wt) p53 were involved in this protein-protein interaction, we generated baculoviral constructs encoding full length or distinct functional domains of both proteins. Full length PARP-1 was simultaneously coexpressed in insect cells with full length wt p53 protein or its distinct truncated fragments and vice versa. Reciprocal immunoprecipitation of Sf9 cell lysates revealed that the central and carboxy-terminal fragments of p53 each were sufficient to confer binding to PARP-1, whereas the amino-terminal part harbouring the transactivation functional domain was dispensable. On the other hand, the amino-terminal and central fragments of PARP-1 were both necessary for complex formation with p53 protein. Since the most important features of p53 protein are regulated by phosphorylation, we addressed the question whether its phosphorylation is essential for the binding between the two proteins. Baculovirally expressed wt p53 was post-translationally modified. At least six distinct p53 isomers were resolved by immunoblotting following two-dimensional separation of baculovirally expressed wt p53 protein. Using specific phospho-serine antibodies, we identified phosphorylation of baculovirally expressed p53 protein at five distinct sites. To define the role of p53 phosphorylation, pull-down assays using untreated and dephosphorylated p53 protein were performed. Dephosphorylated p53 failed to bind PARP-1, indicating that complex formation between the two proteins was regulated by phosphorylation of p53. The marked phosphorylation of p53 at Ser392 observed in unstressed cells suggests that the phosphorylated carboxy-terminal part of p53 undergoes complex formation with PARP-1 resulting in masking of the NES and thereby preventing its export.
Acta Biochim Pol 2005
PMID:Advantage of a baculovirus expression system for protein-protein interaction studies. Involvement of posttranslational phosphorylation in the interaction between wt p53 protein and poly(ADP-ribose) polymerase-1. 1608 9

All organisms sense and respond to conditions that stress their homeostatic mechanisms. Here we review current studies showing that the nucleolus, long regarded as a mere ribosome producing factory, plays a key role in monitoring and responding to cellular stress. After exposure to extra- or intracellular stress, cells rapidly down-regulate the synthesis of ribosomal RNA. Impairment of nucleolar function in response to stress is accompanied by perturbation of nucleolar structure, cell cycle arrest and stabilization of p53. The nucleolar target for down-regulation of rDNA transcription is TIF-IA, an essential transcription factor that modulates the activity of RNA polymerase I (Pol I). Upon stress, TIF-IA is phosphorylated by c-Jun N-terminal kinase 2 (JNK2). Phosphorylation prevents TIF-IA from interaction with Pol I, thereby impairing transcription complex formation and rRNA synthesis. Furthermore, stress-induced inactivation of TIF-IA is accompanied by translocation of TIF-IA from the nucleolus to the nucleoplasm. These findings, together with other data showing stress-induced release of nucleolar proteins to carry out other regulatory functions, reinforce the growing realization that nucleoli orchestrate the chain of events the cell uses to properly respond to stress signals.
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PMID:Cellular stress and nucleolar function. 1620 20


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