Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activating mutations in the K-ras gene are genetic alterations frequently found in human carcinomas, particularly in pancreatic adenocarcinomas. Mutation of the K-ras gene is thought to be an early and important event in pancreatic tumor initiation, but the precise role of the mutant K-Ras proteins in neoplastic progression is still unknown. In the present study, we have characterized the influence of oncogenic K-Ras on the phenotype and on the signal transduction of epitheloid PANC-1 pancreatic carcinoma cells by generating PANC-1 cell clones, which stably express EGFP(enhanced green fluorescent protein)-K-Ras (V12). EGFP-K-Ras (V12)-expressing cells exhibited a more fibroblastoid cellular phenotype with irregular cell shape and disorganized cytokeratin filaments. Moreover, these cells showed a marked enhancement of their migratory and invasive properties. Stable expression of EGFP-K-Ras (V12) down-regulated the activity of Rac1 and RhoA, resulting in reduced subcortical actin filaments and stress fibers, which might contribute to the epithelial dedifferentiation. Characterization of the activity of mitogen-activated protein kinases revealed that EGFP-K-Ras (V12) enhanced the activity of p38, but did not affect the activities of the Raf/MEK/ERK cascade and JNK. While inhibition of either MEK or JNK activity had no effect on EGFP-K-Ras (V12)-induced migration, inhibition of p38 activity markedly reduced EGFP-K-Ras (V12)-induced migration. Collectively, the results suggest that oncogenic K-Ras enhances the malignant phenotype and identify the mitogen-activated protein kinase p38 as a target to inhibit oncogenic K-Ras-induced pancreatic tumor cell migration.
 ...
PMID:Oncogenic K-Ras down-regulates Rac1 and RhoA activity and enhances migration and invasion of pancreatic carcinoma cells through activation of p38. 1625 81

Gene P504S is considered as the most specific for prostatic carcinoma and its protein (alpha-methylacyl coenzyme A racemaze (AMACR/P504S) is higly sensitive and specific marker not only for adenocarcinoma cells but also for preceding changes - prostatic intraepithelial neoplasm (PIN). AMACR/P504S seems to be the first marker of malignant transformation and tumor progression. Use of immunohistochemical method for revealing this marker together with methods of basal prostatic cells observation (cytokeratin of a high molecular weight, cytokeratin 5/6, p63) improves morphological diagnosis of prostatic carcinoma, particularly on the material of needle biopsies. This combination allows one to identify neoplastic nature of some difficult lesions.
 ...
PMID:[Achievements in morphological diagnosis of prostatic cancer: alpha-methylacyl-coenzyme-A-racemase--a new marker of malignant cell transformation]. 1632 73

Patients undergoing resection of hepatic metastases of colorectal cancer have a high risk of extrahepatic recurrence, most likely caused by early tumor cell dissemination or the manipulation of liver tumors during surgical resection. Using immunocytochemistry, we studied 47 patients for cytokeratin (CK)-positive (+) cells in: a) bone marrow (BM) samples to determine whether tumor cell dissemination had already occurred before surgery; and b) blood samples directly taken from the hepatic vein before and during surgery of liver metastases. In addition, normal and malignant liver tissues were evaluated for markers known to be involved in tumor progression and metastasis [urokinase plasminogen activator (uPA), Her-2/neu, epidermal growth factor receptor (EGF-R)] using sandwich enzyme immunoassays. CK+ cells were detected in the BM of 26/47 patients (55%), in blood samples of 14/47 patients (30%) before surgery and 11/47 patients (23%) during surgery with a median detection rate of 1 (range, 1-14) CK+ cell per 4x10(6) MNC. No CK+ cells were found in 15/47 patients (32%) in any sample studied. Tumor tissue was obtained from 32/47 patients and normal liver tissue from 24/32 patients. While no differences were found for EGF-R and Her-2/neu, a 9-fold higher expression of uPA could be demonstrated in tumor tissue of 20/32 patients (63%) compared to normal liver tissue. When all obtained results were correlated with clinical outcome, neither the detection of CK+ cells nor the expression pattern in the tumor tissue, or the combination of both, was predictive for extrahepatic recurrence or overall survival after a mean observation time of 43 months (range, 26-54 months). Although uPa is overexpressed in liver metastases of colorectal cancer, and dissemination of CK+ cells during surgery of these metastases is a frequent event in colon cancer, these findings do not predict extrahepatic recurrence. Further characterization of single cells, especially those spread during surgery, will help to identify those patients with an increased risk of later relapse.
 ...
PMID:Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases. 1639 68

We report a rare case of basaloid squamous cell carcinoma of the lung in a young Japanese woman. An 18-year-old woman presented with productive cough. Chest radiogram and computed tomography (CT) revealed a tumor in the left hilum accompanied by partial atelectasis of the left upper lobe and pleural effusion. Transbronchial fine-needle aspiration cytology supported a tentative diagnosis of primary squamous-cell carcinoma of the lung. The clinical stage was T4N2M1, with multiple bone metastases. Despite a transient response to chemotherapy consisting of carboplatin and paclitaxel, the patient died because of tumor progression 2 months after the start of the chemotherapy. Necropsy established the diagnosis of basaloid squamous-cell carcinoma of the lung. Immunohistochemical studies of the necropsy specimen indicated that the tumor was positive for keratin, vimentin, and S100, and negative for chromogranin A, cytokeratin CAM5.2, and bcl-2. Besides the rarity of the disease itself, the present case seemed to have additional uniqueness in that the patient was 18 years old and female. This is the youngest patient with a case of basaloid squamous cell carcinoma of the lung ever reported.
 ...
PMID:Basaloid squamous-cell carcinoma of the lung in a young woman. 1650 33

Lymphatic metastasis to the regional lymph nodes through the lymphatic vessels is an important indicator of poor prognosis in many types of malignant tumors. Recently, much attention has been paid to lymphangiogenesis for its possible role on tumor progression in various carcinomas. However, morphological evidence that lymphatic vessels actively proliferate in colorectal carcinoma has not been reported. Here, we first devised a triple immunostaining method to detect proliferating lymphatic vessels utilizing antibody to Ki-67 antigen as a marker of cell proliferation, antibody to cytokeratin as an epithelial cell marker, and antibody to podoplanin as a lymphatic vessel-specific marker. Ki-67/podoplanin-immunoreactivity enabled us to identify proliferating lymphatic vessels, while cytokeratin immunoreactivity allowed us to distinguish proliferating lymphatic vessels from Ki-67/cytokeratin-positive carcinoma cells in lymphatic lumens. Analyzing 64 colorectal carcinoma patients' samples using this technique, we showed that both lymphatic vessel density and proliferating activity of lymphatic vessels were significantly increased in colorectal carcinoma tissues compared with their normal counterparts. We then examined the correlation between the degree of lymphangiogenesis and patients' prognosis or clinicopathological variables, but no statistically significant differences were obtained in these analyses. Thus, these results combined together indicate that extensive lymphangiogenesis occurs in colorectal carcinoma, but that the degree of lymphangiogenesis alone is not an independent prognostic factor for this disease.
 ...
PMID:Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance. 1657 16

The prevailing models of cancer metastasis postulate that, after a series of accumulating genetic and epigenetic changes during transformation and invasive growth, the most advanced clone within a primary tumour acquires the critical cellular phenotype enabling dissemination and metastasis. This postulate is particularly based on observations that metastases usually display more genetic changes than the primary tumour. The development of several novel techniques is now enabling experimental testing of the model: The detection of single disseminated cancer cells by epithelial specific antibodies directed against cytokeratin in mesenchymal tissues has become possible even before manifestation of metastasis. After their isolation by micromanipulation comprehensive amplification of the single cell genomes allows the application of several molecular genetic methods for further characterisation. Our first data from single cytokeratin-positive cells that were isolated from the bone marrow of breast cancer patients indicate that the model of cancer progression should be revised. Cancer cells already disseminate in an early stage of genomic development and still have to acquire the critical chromosomal aberrations needed for metastatic outgrowth and full malignant potential. These observations apparently imply consequences for the development of novel adjuvant therapies. The early diversification of primary tumours and disseminated cancer cells precludes a simple extrapolation from local to systemic disease eventually necessitating increasing efforts for the direct analysis of single disseminated cancer cells as the cellular targets of adjuvant therapies.
 ...
PMID:[From single disseminated tumor cells to metastasis insights from molecular genetic analyses of single cells]. 1688 8

Intraductal carcinoma of the prostate (IDC-P) has been described in radical prostatectomies. However, there is limited information as to its histologic features and clinical significance when seen on prostate biopsy. A total of 27 cases of prostate biopsies with only IDC-P (ie no infiltrating cancer anywhere on the biopsy) were studied from the consult files of one of the authors. IDC-P was defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells forming either: (1) solid or dense cribriform patterns or; (2) loose cribriform or micropapillary patterns with either marked nuclear atypia (nuclear size 6 x normal or larger) or comedonecrosis. The numbers of cores involved by IDC-P in the biopsies ranged from 1 to 7, with >1 core involved in 17 cases. The architectural patterns of IDC-P were solid (12), dense cribriform (19), loose cribriform (17), and micropapillary (5). More than one pattern was present in 24 of 27 cases. The cytological features frequently observed in IDC-P were marked pleomorphism (18), non-focal comedonecrosis (22), and mitoses (20). Basal cells were observed on regular hematoxylin and eosin stained slides in 14 cases; in all the cases, basal cells were confirmed by immunohistochemical stains for high molecular weight cytokeratin (n=25) and/or p63 (n = 4). After the diagnosis of IDC-P on prostate biopsies, patients were treated by radical prostatectomy (6), radiation (7), hormone (5), combined radiation and hormone (1), or watchful waiting (2). The follow-up information was not available for six patients. The follow-up times ranged up to 4 years with an average of 2.1 years. In all six radical prostatectomy specimens, high-grade infiltrating carcinoma with Gleason score 8 or 9 was present with five cases also revealing prominent IDC-P. Non-focal extraprostatic extension of carcinoma was observed in five of the six prostatectomy cases with two cases also demonstrating vascular invasion. Three of 16 patients who did not receive radical prostatectomy developed bone metastases. Our study indicates that IDC-P on prostate biopsies is frequently associated with high-grade cancer and poor prognostic parameters at radical prostatectomy as well as potentially advanced disease following other therapies. These findings support prior studies that IDC-P represents an advanced stage of tumor progression with intraductal spread of tumor. Consideration should be given to treat patients with IDC-P on biopsy aggressively even in the absence of documented infiltrating cancer.
 ...
PMID:Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance. 1698 Sep 40

Epithelial-mesenchymal transition (EMT) refers to critical events occasionally observed during tumor progression, including invasion and metastasis, by which cancer cells acquire a fibroblast-like phenotype. Since the stromal cell-derived factor-1 (SDF-1)/CXCR4 system can facilitate lymph node metastasis in oral squamous cell carcinoma (SCC), we have explored the possibility that this system might be involved in EMT. Oral SCC cells, B88 and HNt, which have functional CXCR4 and lymph node metastatic potential, were found to lose their epithelial cell morphology due to SDF-1. In this context, the downregulation of epithelial markers, cytokeratin, E-cadherin and beta-catenin, and the upregulation of mesenchymal marker, vimentin and snail were detected. Furthermore, upregulation of vimentin by treatment with SDF-1 was impaired by phosphatidylinositol 3 kinase (PI3K) inhibitor Wortmannin, but not by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor U0126. In the type I collagen embedding culture, SDF-1-treated B88 cells formed protruding extensions, but the effect was impaired by treatment with Wortmannin. These results suggested that EMT induced by the SDF-1/CXCR4 system might be involved in the lymph node metastasis of oral SCCs via activation of PI3K-Akt/PKB pathway.
 ...
PMID:Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells. 1701 44

Bone marrow (BM) is a prognostically relevant indicator organ of micrometastasis; however, the clinical importance of BM micrometastasis in gastric cancer patients is not yet known. In the present study, the BM of 267 consecutive patients with primary gastric cancer was examined for tumor cells using immunocytochemical techniques. Real-time quantitative RT-PCR was used to ensure that the tumor cells were detected properly. Among the 267 cases analyzed, 30 cases (11.2%) had cytokeratin-positive cells in the bone marrow. Positive findings were related to the tumor stage (P<0.05) and to the prominent depth of invasion (P<0.05). All patients with liver metastasis at operation had cytokeratin-positive cells in the BM. Recurrence of the disease was confirmed in 50 cases (18.7%); 4 of 30 (13.3%) in the cytokeratin-positive group and 46 of 237 (19.4%) in the cytokeratin-negative group. There were no significant differences in the 5-year survival rates between the cytokeratin-positive and cytokeratin-negative groups. Our study shows that BM micrometastasis increases according to tumor progression; however, only a subset of cancer cells may survive in the BM and finally evolve to a clinically apparent disease. Therefore it does not accurately predict the prognosis or recurrence of the disease.
 ...
PMID:Clinical significance of cytokeratin positive cells in bone marrow of gastric cancer patients. 1758 73

Solid tumor metastasis often involves detachment of epithelial carcinoma cells into the vasculature or lymphatics. However, most studies of cytoskeletal rearrangement in solid tumors focus on attached cells. In this study, we report for the first time that human breast tumor cells produce unique tubulin-based protrusions when detached from extracellular matrix. Tumor cell lines of high metastatic potential show significantly increased extension and frequency of microtubule protrusions, which we have termed tubulin microtentacles. Our previous studies in nontumorigenic mammary epithelial cells showed that such detachment-induced microtentacles are enriched in detyrosinated alpha-tubulin. However, amounts of detyrosinated tubulin were similar in breast tumor cell lines despite varying microtentacle levels. Because detyrosinated alpha-tubulin associates strongly with intermediate filament proteins, we examined the contribution of cytokeratin and vimentin filaments to tumor cell microtentacles. Increased microtentacle frequency and extension correlated strongly with loss of cytokeratin expression and up-regulation of vimentin, as is often observed during tumor progression. Moreover, vimentin filaments coaligned with microtentacles, whereas cytokeratin did not. Disruption of vimentin with PP1/PP2A-specific inhibitors significantly reduced microtentacles and inhibited cell reattachment to extracellular matrix. Furthermore, expression of a dominant-negative vimentin mutant disrupted endogenous vimentin filaments and significantly reduced microtentacles, providing specific genetic evidence that vimentin supports microtentacles. Our results define a novel model in which coordination of vimentin and detyrosinated microtubules provides structural support for the extensive microtentacles observed in detached tumor cells and a possible mechanism to promote successful metastatic spread.
 ...
PMID:Vimentin filaments support extension of tubulin-based microtentacles in detached breast tumor cells. 1863 20


<< Previous 1 2 3 4 5 6 7 Next >>