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Biomedical subjects

T M Weiner

Publications and source records attributed to T M Weiner.

8 recordsLinked to original sources

Measuring advanced practice nursing outcomes.

The measurement of outcomes has become an important component of evaluating health care. Although it is clear that measuring outcomes is necessary to establish the effectiveness of advanced practicing nursing, which outcome measures to use and how to conduct an effective outcomes assessment remain unclear. The purpose of this article is to present an overview of advanced practice nursing outcomes research, review outcome measures important to advanced practice nurses (APNs), and discuss sources of outcome measures and instruments that can be used by APNs to establish the effectiveness of the role.

Acute Disease↗

Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors.

The focal adhesion kinase (FAK) gene encodes a tyrosine kinase (p125FAK) thought to be involved in signal transduction pathways used in cell adhesion, motility, and anchorage-independent growth. Because alterations in these cellular processes occur in tumor invasion and metastasis, we studied the protein expression of FAK in a variety of human tumors and found that in the 119 samples studied, increased levels of p125FAK correlated with the invasive potential of a tumor. By comparing FAK expression in tumors with normal tissue from the same patient, we found that p125FAK was significantly elevated in 17 (100%) of 17 invasive and metastatic colonic lesions and in 22 (88%) of 25 invasive and metastatic breast tumors. Additional studies of FAK expression in 13 high grade sarcomas showed high levels in all samples compared to benign, noninvasive mesenchymal specimens. Furthermore, FAK protein levels were elevated in preinvasive lesions, such as large (> 2 cm) colonic villous adenomas, whereas noninvasive, yet hypercellular, neoplastic tissues such as parathyroid and hepatocellular adenomas did not overexpress FAK. These data provide evidence that both epithelial and mesenchymal tumor progression are accompanied by increased p125FAK expression and suggest that the level of FAK expression might be a marker for the invasive potential of a tumor.

Adenofibroma↗

Receptor tyrosine kinases expressed in metastatic colon cancer.

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the alpha and the beta forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the alpha-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease.

Amino Acid Sequence↗

Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors.

BACKGROUND: The tyrosine kinases are a family of genes that includes many growth factor receptors and protooncogenes. They appear to have a role in many cancers, but have not been systematically studied in the pathogenesis and progression of human sarcomas. METHODS: To characterize the protein tyrosine kinases that are expressed in human sarcomas, we used a polymerase chain reaction (PCR)-based method to construct kinase-specific cDNA libraries from low-grade and high-grade primary tumors. Thereafter, individual tyrosine kinase gene expression was assessed in a panel of sarcoma cell lines and primary tumors using Northern blotting and PCR. RESULTS: We identified 19 species of tyrosine kinase genes, including many growth factor receptors, the human homolog of the focal adhesion kinase (FAK) gene, and a novel trk-related kinase designated HGK2. Messenger RNA expression analyses showed relative overexpression of the two forms of the platelet-derived growth factor receptors (PDGFRs) with expression of the alpha form restricted to a subgroup of high-grad and metastatic sarcomas. We were unable to demonstrate coexpression of the PDGF isoforms in primary tumors that overexpressed the receptors, suggesting that a PDGF/PDGFR autocrine pathway may not be a central mechanism in the malignant transformation of sarcomas in vivo. FAK expression was observed in a variety of sarcomas, with increased levels in several high-grade and metastatic leiomyosarcomas. CONCLUSIONS: When grouped together by histologic cell type and grade, the expression data of the 19 kinases in primary tumors described a greater degree of heterogeneity than is generally appreciated by clinicopathologic classification schemes. This diversity suggests that sarcomas, even those that appear to be clinically similar, arise through a variety of molecular pathways involving tyrosine kinases.

Amino Acid Sequence↗

Expression of focal adhesion kinase gene and invasive cancer.

The focal adhesion kinase (FAK) gene produces a tyrosine kinase that localises to contact points between cells and extracellular matrix. It is believed to be an important signal molecule in cell adhesion. We have isolated a human homologue of the FAK gene from primary sarcomas and looked for FAK mRNA in 49 human tissue samples, including paired normal and neoplastic samples. We found increased levels of FAK in 1 of 8 adenomatous tissues, in 17 of 20 invasive tumours, and in all 15 metastatic tumours. There was no detectable FAK mRNA in 6 normal tissue samples. These observations suggest that FAK overexpression may accompany changes in signal pathways involved in tumour cell invasion.

Breast Neoplasms↗

Novel protein kinases expressed in human breast cancer.

The family of protein kinases includes many oncogenes and growth-factor receptors, as well as genes that are involved in cell-cycle regulation. We have identified protein kinases expressed in a human breast-cancer cell line, 600PEI, and a primary human breast carcinoma, using PCR cloning techniques based on consensus sequences in the kinase domain. Twenty-five different protein kinases were isolated, including 3 novel putative tyrosine kinases (designated TK1, TK2, and TK5), and 2 novel putative cell-cycle-associated serine/threonine kinases (designated STK1 and STK2). TK1 is a new member of the src family of kinases that is expressed predominantly in epithelial cells. TK2 is homologous to the receptor kinase, HEK, and TK5 appears to be another member of the JAK family of kinases. The novel serine/threonine kinases, designated STK1 and STK2, were homologous to the human cdc2 and the Aspergillus nimA genes. We subsequently analyzed the levels of expression of all of these protein kinases in a panel of human breast carcinomas, using PCR-based methods. This analysis revealed different expression profiles in different primary breast carcinomas and, therefore, may determine new molecular sub-sets of human breast cancer.

Amino Acid Sequence↗

Long term results of percutaneous catheter drainage of pancreatic pseudocysts.

Percutaneous catheter drainage (PCD) has become an established and often preferred alternative to surgical treatment in the management of pancreatic pseudocysts. However, the long term results of percutaneous drainage of pancreatic pseudocysts remain uncertain. In an effort to determine the long term outcome of this therapy, 42 patients undergoing PCD of a pancreatic pseudocyst were analyzed retrospectively. Forty-two pancreatic pseudocysts were drained percutaneously in 42 patients. Sixty-seven percutaneous drainage procedures were performed--22 patients underwent one, 15 had two and five patients required three procedures. Percutaneous drainage was considered not to be effective when the pseudocyst persisted or when it recurred after initial resolution. Twenty-three pseudocysts were infected at the time of drainage and 19 were not infected. In 30 patients, the cause of the pseudocyst was alcoholic pancreatitis. There were no deaths related to the procedures and seven complications occurred, including hemorrhage, pancreatic fistula and empyema. Mean follow-up evaluation time of the patients was ten months. In nine patients, the pseudocyst was successfully drained and resolved. There were 33 treatment failures, among which 26 pseudocysts failed to resolve and seven recurred after initial resolution. Eventually, 25 patients underwent a surgical procedure, 20 for persistent pseudocyst and five for recurrence. Using contingency table analysis, the size of the pseudocyst, amount of fluid drained, amylase concentration in the aspirate, presence of infection, number of drainage procedures performed and duration of catheter drainage had no influence on the likelihood of success in long term pseudocyst resolution after PCD. Pseudocysts not related to alcoholic pancreatitis seemed to be less likely (p < 0.05) to resolve with percutaneous drainage than those caused by alcohol. PCD is a safe and valuable procedure in the acute management of patients with pancreatic pseudocyst. However, the current data suggest that despite early success with percutaneous drainage, the lack of resolution and recurrence rate of pancreatic pseudocyst is high. Therefore, it should not be considered as the definitive form of therapy in most patients. Close surveillance of patients undergoing percutaneous drainage and communication between surgeons and radiologists are critical in the management of pancreatic pseudocysts.

Adult↗