Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the past 5 years, research has increasingly addressed molecular alterations in prostate cancer (CaP). Mutations of tumor suppressor gene p53 have been found in a variety of cancers, including urologic neoplasms. Several studies have been conducted on CaP specimens, citing frequencies of p53 alterations in localized cancers ranging from 4 to 60% and with more advanced hormone refractory disease, as high as 94%. The majority of studies have revealed a low percentage of p53 abnormalities in early-stage (clinically organ-confined) CaP. The overwhelming bulk of evidence suggests that the frequency of p53 abnormalities does increase with disease progression and is highest in tissues from patients with hormone-refractory prostate cancer. More recently, our group and others have found that focal p53 expression in the primary tumor by immunohistochemistry is predictive of cancer recurrence after radical prostatectomy. bcl-2 is an oncogene critically involved in the apoptosis, or programmed cell death. Overexpression of bcl-2 protein by immunohistochemistry has been commonly detected in advanced hormone refractory CaP. Our group recently has also shown that bcl-2 protein expression in primary CaP is a predictor of cancer recurrence after radical prostatectomy. Furthermore, the combination of p53 and bcl-2 protein expression were both independent predictors of recurrence after surgery. Most recently, we have shown that even though p53 and bcl-2 are predictive biomarkers when sampling the radical prostatectomy specimen, they are not useful to predict postoperative recurrence when sampling the pretreatment needle biopsy. Ki-67 is an antigen of cellular proliferation. Immunohistochemical staining for Ki-67 in archival material can be performed using the MIB-1 antibody. Unlike our results with p53 and bcl-2, Ki-67 protein expression by immunohistochemistry using MIB-1 was not an independent prognostic marker for cancer recurrence after radical prostatectomy although it may have clinical utility in subsets of patients. Assessment of MIB-1 staining in CaP needle biopsy samples is underway. Tumor neovascularity, or angiogenesis, is necessary for cancers to grow and metastasize. Angiogenesis in CaP as a prognostic marker has received recent attention. Most studies have used factor VIII immunohistochemical staining and increased angiogenesis has been suggested as a staging and prognostic marker. Our group has recently conducted a large study of radical prostatectomy patients and used CD34 antigen immunohistochemistry to assess neovascularity. We did not find that this biomarker assessment was an independent prognostic marker of cancer recurrence after radical prostatectomy. Further work is being conducted in needle biopsy samples. More research is needed to assess new biomarkers and, most importantly, to standardize the methodology for sampling and assaying biomarkers in heterogeneous and multifocal prostate cancer.
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PMID:Angiogenesis, p53, bcl-2 and Ki-67 in the progression of prostate cancer after radical prostatectomy. 1032 96

Between 1995 and 1998, we treated 5 patients with anti-factor VIII antibodies and spontaneous bleeding. All patients had underlying malignant conditions. Initial control of the bleeding episodes and reduction in inhibitor titer was achieved in all patients. Disappearance of factor VIII inhibitor occurred in 3 patients after either resection of the tumor or chemotherapy. Immunosuppression therapy failed to eradicate the antibody in 2 patients with metastatic disease. Antibodies against factor VIII appearing in certain patients may be directly associated with the underlying malignancy, rather than a coincidental finding. Attempts to reduce the titer or eradicate the inhibitor may fail if recognition of the underlying condition is not sought, or an appropriate treatment of cancer is not offered.
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PMID:Antibodies against factor VIII in patients with solid tumors: successful treatment of cancer may suppress inhibitor formation. 1042 73

With the use of antibodies against factor VIII, vascular bed (number, surface and caliber of vessels) was studied in 64 cases of invasive ductal carcinoma and in normal breast tissue. The trend to a decrease of the vessels number with growing size of the tumor and emergence of lymph node metastases was observed. No difference was found in the development of vascular bed depending on the degree of malignancy, clinical course, tumor or normal breast tissue.
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PMID:[Stromal vessels of invasive ductal mammary gland carcinoma]. 1047 46

We investigated the effect of VIP on the liver metastases and angiogenesis by Colon 26-L5 carcinoma cells in mice. Daily systemic administration of VIP, beginning 3 days after tumor inoculation into a portal vein of mice, inhibited significantly the development of their liver metastases. Immunohistochemical staining for factor VIII-related antigen in the sections of liver metastases showed that the systemic administration of VIP caused significant prevention of angiogenesis within tumor masses. VIP (10-(10) to 10(-6) M) inhibited the invasion of reconstituted basement membrane (Matrigel) by hepatic sinusoidal endothelial (HSE) cells in a concentration-dependent manner in a Transwell chamber assay in vitro and achieved approximately 50% reduction of control at 10(-6) M. VIP (10(-6) M) also significantly suppressed the haptotactic migration of HSE cells to fibronectin, laminin or type I collagen substrates with a similar inhibition rate to the invasion assay. Exposure of VIP to HSE cells induced accumulation of intracellular cAMP in a concentration-dependent manner. The inhibitory effect of VIP (10(-6) M) on HSE cell migration was significantly abrogated in the presence of 3 x 10(-6) M H-89, a cAMP-dependent protein kinase inhibitor. VIP (10(-6) M) inhibited the morphogenesis of HSE cells into capillary-like structures on Matrigel-coated wells. VIP did not affect the proliferation of HSE cells and the production of gelatinases in HSE cells in vitro at the concentrations used in the invasion assay. These observations suggest that the anti-metastatic effect of VIP on liver metastases by Colon 26-L5 carcinoma cells in mice is partly due to the prevention of tumor angiogenesis probably through suppression of the motility of endothelial cells.
Clin Exp Metastasis 1999 Jun
PMID:Inhibition by vasoactive intestinal polypeptide (VIP) of angiogenesis induced by murine Colon 26-L5 carcinoma cells metastasized in liver. 1054 14

A primary angiosarcoma of the femur arose in continuity with a bone infarct in a 74-year-old man. The tumor, resected by amputation, had pleomorphic polygonal and spindle cells in solid and cystic patterns with focal vasoformative features. The immunohistochemical stains CD31, CD34, factor VIII-related antigen, and Ulex europeus corroborated the endothelial differentiation of the tumor. The patient died after developing pulmonary metastases. This is the oldest reported patient with a well-documented angiosarcoma associated with a bone infarct.
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PMID:Angiosarcoma arising in a bone infarct. 1059 89

In a patient with gastric cancer (GC) associated with one synchronous and three metachronous hepatic metastases (HM), who underwent four hepatectomies, we carried out histochemical investigations regarding cell proliferation, apoptosis, and angiogenesis in the GC and HM. Tissue samples were taken from the primary GC and four HM. Ki-67 immunostaining was performed to evaluate cell proliferation and determine the labeling index (Ki-67 LI; ie, the percentage of cancer cells with nuclei stained for Ki-67). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) was performed to evaluate apoptosis and determine the apoptotic index (ie, the percentage of TUNEL-positive cells), and immunostaining for factor VIII-related antigen was performed to evaluate angiogenesis and measure microvessel density (MVD). The Ki-67 LI was 43.2% in the primary GC and 39.9% in the synchronous HM, and the LI increased with the number of resections of metachronous HM. The apoptotic index was 3.36% in the primary GC, and 5.30% in the synchronous HM, and the index decreased after further resections of the metachronous HM. The MVD was 35 in the primary GC, and 22 in the synchronous HM, and it increased with the number of resections of metachronous HM. The primary GC in this patient may have strongly influenced the growth of HM through effects on cell proliferation, apoptosis, and angiogenesis.
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PMID:Four resections for hepatic metastasis from gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis. 1068 Jun 71

A retrospective study of surgically resectable esophageal cancers was undertaken to determine the relationship between angiogenesis score and growth factor expression with tumor size, histology, degree of differentiation, depth of invasion, nodal disease, and the presence of Barrett's esophagus. The office and hospital charts of 27 patients who had esophageal resection for carcinoma between 1990 and 1995 at Rush-Presbyterian-St. Luke's Medical Center were reviewed. Data collection included patient demographics, survival, tumor size, histology, differentiation, depth of invasion, nodal metastases, and the presence of Barrett's esophagus. The pathology specimens were immunostained for von Willebrand factor (factor VIII-related antigen). Immunostaining was also performed for vascular endothelial growth factor and transforming growth factor alpha. Twenty normal esophageal specimens served as controls. Angiogenesis score was determined by counting vessels under conventional light microscopy at x200 magnification, and growth factor expression was graded on a scale of 1 to 4. Cancers had higher angiogenesis and growth factor expression than controls (P = 0.01). Patient age, tumor size, histology, differentiation, depth of invasion, and Barrett's esophagus did not correlate with angiogenesis score or tumor growth factor expression. Lymph node status did correlate with both angiogenesis score and growth factor expression (P < or = 0.02). We conclude that high angiogenesis score and growth factor expression correlate with the presence of lymph node metastases. This may help select patients for preoperative radiation and chemotherapy or determine the extent of surgery performed for esophageal carcinoma.
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PMID:Do angiogenesis and growth factor expression predict prognosis of esophageal cancer? 1077 79

Members of the matrix metalloprotease (MMP) family are implicated in the progression of several malignancies including prostate cancer due to their ability to break down extracellular matrix (ECM) components. In this study, we have evaluated the ability of a synthetic MMP inhibitor (A-177430) to block tumor growth and metastases in a syngeneic model of rat prostate cancer. In an in vitro substrate assay, A-177430 exhibited nanomolar potency (IC(50) 2-6 nM) against the enzymatic activity of several MMPs. For in vivo studies, male Copenhagen rats were injected s.c. with Mat Ly Lu rat prostate cancer cells (1 x 10(6) cells ) into the right flank and animals were administered i.p.with different doses (10-100 mg/kg per day) of A-177430 for 16 days. Administration of A-177430 resulted in a dose-dependent decrease in tumor volume as compared to a control group of animals receiving vehicle alone. The maximum dose (100 mg/kg per day) of A-177430 exhibited complete arrest in tumor growth and prevented the development of macroscopic tumor metastases to lungs without exhibiting any noticeable side effects. Histologic examination of primary tumors from experimental animals showed extensive tumor necrosis and decreased tumor angiogenesis as determined by factor VIII staining of primary tumors following A-177430 treatment. These primary tumors from experimental animals also exhibited a significant increase in tumor cell DNA fragmentation as determined by TUNEL assay. Collectively, these results demonstrate the ability of MMP inhibitors to block tumor growth and metastases by blocking ECM degradation and by inhibiting tumor angiogenesis and promotion of prostate cancer cell apoptosis in vivo.
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PMID:Synthetic inhibitor of matrix metalloproteases decreases tumor growth and metastases in a syngeneic model of rat prostate cancer in vivo. 1086 87

Urokinase plasminogen activator (uPA) plays an important role in the progression of several malignancies including breast cancer. We have identified a noncompetitive antagonist of the uPA-uPAR interaction derived from a nonreceptor binding region of uPA (amino acids 136-143). This 8-mer capped peptide (A6) inhibited breast cancer cell invasion and endothelial cell migration in a dose-dependent manner in vitro without altering cell doubling time. Intraperitoneal administration of A6 resulted in a significant inhibition of tumor growth and suppressed the development of lymph node metastases in several models of breast cancer cell growth and metastasis. Large areas of tumor necrosis and extensive positive staining by TUNEL were observed on histological and immunohistochemical analysis of experimental tumor sections from A6-treated animals. A6 treatment also resulted in a decrease in factor VIII-positive tumor microvessel hot-spots. These results identify a new epitope in uPA that is involved in the uPA-uPAR interaction and indicate that an antagonist based on this epitope is able to inhibit tumor progression by modulating the tumor microenvironment in the absence of direct cytotoxic effects in vivo.
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PMID:A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo. 1087 33

The clinical and pathological features of four cases of feline intestinal haemangiosarcoma are described. All cases were in domestic shorthaired cats and the mean age of the animals (n=3) was 13 years. The tumours originated in the colon, small intestine, ileocaecocolic junction or rectum. The rectal tumour was juxtaposed with an adjacent mast cell neoplasm. Metastasis to mesenteric lymph node occurred in two cases, and in one of these cats there was also abdominal seeding. The histopathological appearance was of a spindle cell neoplasm with vascular differentiation in each case. Immunohistochemical staining for factor VIII-related antigen, an endothelial cell marker, confirmed all four tumours to be of endothelial origin. The neoplastic endothelial cells lining irregular vascular channels were more likely to express the antigen than those forming denser sheets without obvious vascular differentiation.
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PMID:Intestinal haemangiosarcoma in the cat: clinical and pathological features of four cases. 1102 28


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