Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Naturally occurring liver disease in dogs resemble human liver disease in great detail; including the activation of liver progenitor cells (LPC) in acute and chronic liver disease. The aim of the present study was to isolate, culture, and characterize progenitor cells derived from healthy mature dog livers. A nonparenchymal cell fraction enriched with small hepatocytes was isolated and cultured in Hepatozyme-serum-free media (SFM) to stimulate the growth of colony-forming small epithelial cells. After 2 weeks of culturing, clonal expansion of keratin 7 (K7) immunopositive small cells with a large nucleus/cytoplasm ratio emerged in the hepatocyte monolayer. These colonies expressed genes of several hepatocyte (CYP1A1, ALB, and KRT18), cholangiocyte/LPC (KRT7 and KRT19), and progenitor cell markers (alpha-fetoprotein, CD44, prominin1, KIT, THY1, and neural cell adhesion molecule 1), indicating their immature and bipotential nature. Gene-expression profiles indicated a more pronounced hepatic differentiation in Hepatozyme-SFM compared to William's Medium E (WME). Furthermore, colony-forming cells differentiated toward intermediate hepatocyte-like cells with a more pronounced membranous K7 immunostaining. In conclusion, colony-forming small epithelial cells in long-term canine liver cell cultures express LPC markers and have differentiating capacities. These cells may therefore be considered as progenitor cells of the liver.
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PMID:In vitro differentiation of liver progenitor cells derived from healthy dog livers. 1845 98

Acute myeloid leukemia with t(8;21)(q22;q22) is a distinct type of leukemia considered to have a favorable prognosis. However, some patients rapidly succumb to disease despite chemotherapy. We studied 56 patients with acute myeloid leukemia associated with t(8;21) and correlated clinicopathologic, cytogenetic and molecular findings with outcome to identify markers of prognosis. In a subset of patients, we also assessed the status of the c-KIT, FLT3 and RAS genes. There were 31 men and 25 women, with a median age of 38 years (range 4-76). The follow-up period ranged from 17 to 104 months (median 52). At the last follow-up, 29 patients had died, 25 patients were in complete remission and two patients were alive with disease. The median survial was 38 months. The 5-year overall survival rate of newly diagnosed patients was 56%. Most patients (39/56, 70%) had chromosomal aberrations in addition to t(8;21), with loss of a sex chromosome (39%) being most common followed by del(9q)(q21-22) (11%) and trisomy 8 (7%). These aberrations, however, did not predict survival. C-KIT (D816V or D816Y), FLT3 (ITD or D835) and RAS mutations were detected in 26, 10 and 7%, respectively, of cases assessed. The 5-year overall survival rate of patients with mutated leukemia was 20%. No mutations were observed in three patients who died within 7 months of diagnosis. Leukocytosis or CD56 expression did not correlate with a poor survival nor did the levels of CD19 expression predict c-KIT mutation status. We conclude that acute myeloid leukemia associated with t(8;21) is a heterogeneous disease with poor survival in a subset of patients unrelated to common secondary cytogenetic aberrations.
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PMID:Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogenetic aberrations. 1853 54

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader to the basic information about the field. We describe selected stem cell isolation techniques and stem cell markers for various stem cell populations. These include makers for endothelial progenitor cells (CD146/MCAM/MUC18/S-endo-1, CD34, CD133/prominin, Tie-2, Flk1/KD/VEGFR2), hematopoietic stem cells (CD34, CD117/c-Kit, Sca1), mesenchymal stem cells (CD146/MCAM/MUC18/S-endo-1, STRO-1, Thy-1), neural stem cells (CD133/prominin, nestin, NCAM), mammary stem cells (CD24, CD29, Sca1), and intestinal stem cells (NCAM, CD34, Thy-1, CD117/c-Kit, Flt-3). Separate section provides a concise summary of recent clinical trials involving stem cells directed towards improvement of a damaged myocardium. In the last part of the review, we reflect on the field and on future developments.
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PMID:Adult stem cells and their trans-differentiation potential--perspectives and therapeutic applications. 1862 66

Mutations of the receptor tyrosine kinase (RTK) are frequently reported in acute myeloid leukemia (AML) with a normal karyotype. In this study, Southeast Asian AML patients with a favorable karyotype including t(8;21)/AML-ETO, inv(16)(CBF beta/SMMHC), and t(15;17)/PML-RAR alpha were genotyped for KIT and FLT3 RTK mutations by PCR and sequencing. The combined frequency of KIT/FLT3 mutations in patients with t(8;21), inv(16) and t(15;17) was 35%, 18% and 41%. KIT mutations were mainly detected in patients with t(8;21) (23%) and undetectable in patients with t(15;17). Two novel KIT mutations were identified. FLT3 mutations were preferentially found in patients with t(15;17) (41%). Patients with inv(16) had a strikingly low frequency of both KIT and FLT3 mutations (9% each). KIT-mutated patients were older than FLT3-mutated patients and demonstrated a high expression of myeloid antigens and CD56 lymphoid antigen. FLT3 mutation was coexistent with PML-RAR alpha with markedly low or no CD11c and HLA-DR expression. KIT and FLT3 mutations preferentially exist in distinct clinical and genetic AML subtypes, reflecting unique leukemogenetic mechanisms. Targeting therapy with specific RTK inhibitors should provide benefits for a subgroup of AML patients with favorable chromosomes who also carry selective types of RTK mutations.
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PMID:KIT and FLT3 receptor tyrosine kinase mutations in acute myeloid leukemia with favorable cytogenetics: two novel mutations and selective occurrence in leukemia subtypes and age groups. 1897 45

The author reports herein an extremely rare case of primary small cell carcinoma of the mediastinum with an emphasis on KIT and PDGFRA genes. A 66-year-old man was found to have a mediastinal tumor on a routine chest X-ray examination, and was admitted to our hospital. Imaging modalities revealed a 5 x 4 cm tumor in the middle mediastinum near the bronchial carina. No other tumors were detected in the body including the lungs. Video-assisted thoracoscopy confirmed the mediastinal tumor, and a large incisional biopsy was performed. The tumor was histologically small cell carcinoma. An immunohistochemical study revealed positive reactions for cytokeratins (AE1/3, polyclonal), synaptophysin, neuron-specific enolase, CD56, KIT, and PDGFRA, and negative reactions for chromogranin, CEA, CD45, CD20, and CD3. Ki-67 labeling showed a value of 80%. A molecular genetic analysis using PCR-direct sequencing identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The patient received radiation and chemotherapy, and the tumor was fully resolved. The patient has remained free of recurrence for 6 years after the first presentation. The present case is the first reported case of primary small cell carcinoma of the mediastinum with an examination of KIT and PDGFRA expressions and KIT and PDFGRA gene mutations.
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PMID:Primary small cell carcinoma of the mediastinum: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes. 1898 97

Primary pure neuroendocrine breast carcinomas (NEBC) have been considered special features within conventional breast carcinomas until recently. Indeed, the actual incidence of NEBC in BC populations has remained largely unknown due to the lack of unambiguous diagnostic criteria. In 2003, the World Health Organization (WHO) classification of breast tumors definitely established that the immunohistochemical expression of NE markers in more than 50% of the tumor cell population is the unique requisite for NEBC diagnosis. Herein, we sought to determine the incidence, the clinico-pathological features and the immunohistochemical profile of NEBC in a large series of 1368 infiltrating breast tumors collected from 1989 to 2008 in our institution (Dr Josep Trueta University Hospital, Girona, Catalonia). Twelve cases were initially selected to fulfil histopathological patterns compatible with NEBC. Clinical data along with histological and immunohistochemical profiles were collected in all cases. The criterion inclusion was the presence of more than 50% tumor immunoreactivity for one of NE markers including chromogranin, synaptophysin and CD56. Only 7 tumors fully satisfied the NEBC criteria established by the WHO (0.5% prevalence). All the NECB were grade 2 ductal carcinoma infiltrating (DCI) with tumor sizes ranging from 7 to 55 mm. Lymphovascular tumoral emboli was present in 4 cases (57.1% of NEBC) and mucinous features occurred in 2 cases (28.5% of NEBC). Axillary lymph nodes were metastatic in 3 cases (42.8% of NEBC). A positive status for estrogen receptor (ER), progesterone receptor (PR) and synaptophysin was observed in 7 cases (100% of NEBC). None of the NEBC displayed HER2 overexpression. All the patients bearing NECB received hormone therapy and 4 of them underwent radiotherapy and/or chemotherapy. Of note, none of the NEBC patients died from BC-related causes after a median follow-up of 51 months. These findings revealed that: a) Pure solid NEBC do not significantly differ from other breast carcinomas in terms of general clinical features; b) NEBC do not exhibit an aggressive behavior despite the presence of adverse prognostic factors; and c) NEBC immunohistochemical profile mainly corresponds to that of the Luminal A BC subtype. Although it remains to be elucidated whether the good prognosis of NEBC relates to the intrinsic nature of the tumor and/or to a high rate of treatment responses, their immunohistochemical profile strongly suggest that NEBC belong to the Luminal A BC subtype. Forthcoming studies should definitely determine if the clinico-pathological features of NEBC indeed represent an independent good-prognosis subgroup of BC gene signature.
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PMID:Solid neuroendocrine breast carcinomas: incidence, clinico-pathological features and immunohistochemical profiling. 1902 Jul 16

A case of CD30-positive microvillous lymphoma (MVL) in an 87-year-old man who was encountered generalised lymphadenopathy is presented. Histopathologically, the tumour showed a morphological mimic of anaplastic large cell lymphoma (ALCL) with sinusoidal growth pattern. Immunohistochemically (IHC), the tumour cells were CD30(+), CD20(+), CD45(+), BCL-2(+), BCL-6(+), MUM1(+), Ki-67(+), CD45RO(-), CD3(-), CD10(-), CD15(-), CD56(-), EMA(-), TIA-1(-) and ALK(-). Flow cytometry confirmed the IHC. In situ hybridisation for Epstein-Barr virus RNA was negative. Electron microscopically, the tumour cells were similar to large transformed lymphocytes and had circumferentially profuse microvillous projections resembling those of epithelial mesothelioma cells. In conclusion, CD30-positive MVLs are indistinguishable from ALCLs that have ultrastructural microvillous projections by morphology alone. However, the lack of EMA, TIA-1 and ALK expression in this MVL case facilitated a definite distinction from ALCLs. The results of a panel of three markers (CD10(-), Bcl-6(+) and MUM1(+)) suggested that the present case of CD30-positive MVLs has an activated non-germinal centre B-cell origin.
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PMID:CD30-positive diffuse large B-cell lymphoma with microvillous features: so-called microvillous lymphoma. 1912 65

The decidual microenvironment is characterized by a unique population of leukocytes composed primarily of CD56(bright) NK cells and macrophages. The latter are situated near trophoblast cells at the fetal-maternal interface and there is evidence that trophoblast cells are capable of recruiting macrophages to this site. This study sought to determine the role of tumour necrosis factor alpha (TNF) in the trophoblast-mediated recruitment of monocyte-derived macrophages to the fetal-maternal interface. The human first trimester extravillous trophoblast cell line HTR-8/SVneo was shown to express TNFR1 and to secrete the monocyte-attracting chemokines CCL2 and CCL5 after exposure to TNF in a dose-dependent manner. TNF-mediated stimulation of CCL2 secretion was completely inhibited by incubating the trophoblast cells with the p38-MAPK inhibitor SB203580, whereas CCL5 secretion was inhibited by treating the trophoblast cells with inhibitors specific for JNK (SP600125) and ERK kinase (U0126). Media conditioned by TNF-treated trophoblast cells significantly enhanced the ability of the monocyte cell line THP-1 to invade through Matrigel, and this effect was inhibited using antibodies specific for CCL2 and CCL5. These results support a role for TNF at the fetal-maternal interface as a regulator of macrophage recruitment by trophoblast cells.
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PMID:Tumour necrosis factor alpha stimulates the production of monocyte chemoattractants by extravillous trophoblast cells via differential activation of MAPK pathways. 1920 63

Glioblastoma multiforme (GBM) represents an extremely chemoresistant tumour type. Here, authors analysed the immunophenotype of GBM tumours by flow cytometry and correlated the immunophenotypic characteristics with sensitivity to chemotherapy. The expression of selected neural and non-neural differentiation markers including A2B5, CD34, CD45, CD56, CD117, CD133, EGFR, GFAP, Her-2/neu, LIFR, nestin, NGFR, Pgp and vimentin was analysed by flow cytometry in eleven GBM (WHO gr.IV) patients. The sensitivity of tumour cells to a panel of chemotherapeutic agents was tested by the MTT assay. All tumours were positive for A2B5, CD56, nestin and vimentin. CD133, EGFR, LIFR, NGFR and Pgp were expressed only by minor tumour cell subpopulations. CD34, CD45, CD117, GFAP and Her-2/neu were constantly negative. Direct correlations were found between the immunophenotypic markers and chemosensitivity: A2B5 vs lomustine (r(2) = 0.642, P = 0.033), CD56 vs cisplatin (r(2) = 0.745, P = 0.013), %Pgp(+) vs vincristine (r(2) = 0.846, P = 0.008), and %NGFR(+) vs daunorubicine (r(2) = 0.672, P = 0.047) and topotecan (r(2) = 0.792, P = 0.011). In contrast, inverse correlations were observed between: EGFR vs paclitaxel (r(2) = -0.676, P = 0.046), CD133 vs dacarbazine (r(2) = -0.636, P = 0.048) and LIFR vs daunorubicine (r(2) = -0.878, P = 0.004). Finally, significant associations were also found among sensitivities to different chemotherapeutic agents and among different immunophenotypic markers. In conclusion, histopathologically identical GBM tumours displayed a marked immunophenotypic heterogeneity. The expression of A2B5, CD56, NGFR and Pgp appeared to be associated with chemoresistance whereas CD133, EGFR and LIFR expression was characteristic of chemosensitive tumours. We suggest that flow cytometric imunophenotypic analysis of GBM may predict chemoresponsiveness and help to identify patients who could potentially benefit from chemotherapy.
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PMID:Flow cytometry analysis of neural differentiation markers expression in human glioblastomas may predict their response to chemotherapy. 1928 88

The author reports a rare autopsy case of primary small cell carcinoma of the urinary bladder with an emphasis on KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. An 81-year-old man was admitted to Shizuoka City Shimizu Hospital because of dysuria. Cytology of the urine showed small carcinoma cells. Transurethral bladder tumorectomy indicated small cell carcinoma, and the patient was treated by radiation and chemotherapy. The patient died, however, of systemic metastasis 2 months after the first presentation. An autopsy showed a bladder small cell carcinoma and it systemic metastasis. Immunohistochemistry of the tumorectomy and autopsy specimens was positive for cytokeratins, neuron-specific enolase, synaptophysin, CD56, KIT and PDGFRA, and negative for chromogranin and thyroid transcriptional factor-1. Polymerase chain reaction-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) or PDGFRA (exons 12 and 18) genes in the tumorectomy specimens and was non-contributory due to DNA damage in autopsy specimens. The present case is the first case of primary small cell carcinoma of the urinary bladder involving examination of KIT and PDGFRA expression and KIT and PDGFRA gene mutations.
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PMID:Autopsy case of primary small cell carcinoma of the urinary bladder: KIT and PDGFRA expression and mutations. 1935 68


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