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D Albo

Publications and source records attributed to D Albo.

At least 19 recordsLinked to original sources
PubMed2004

Thrombospondin-1 up-regulates tumor cell invasion through the urokinase plasminogen activator receptor in head and neck cancer cells.

BACKGROUND: We have previously demonstrated that thrombospondin-1 (TSP-1) is expressed in squamous cell carcinomas of the head and neck. We have also shown that TSP-1 promotes tumor cell invasion through up-regulation of the urokinase plasminogen activator receptor (uPAR), in adenocarcinoma models. We now determined the role of TSP-1 in the regulation of uPAR expression and tumor cell invasion in squamous cell carcinoma of the head and neck cells. MATERIALS AND METHODS: KB squamous cell carcinoma of the head and neck cells were used. The effect of TSP-1 on uPAR and its ligand, urokinase plasminogen activator (uPA), expression were determined by ELISA. The effect of TSP-1 on KB tumor cell invasion was determined in a modified Boyden chamber collagen invasion assay. To determine the role of uPAR on TSP-1-mediated KB tumor cell invasion, we used the three following different strategies: (a). blocking uPAR or its ligand, uPA, with neutralizing antibodies; (b). enzymatic cleavage of uPAR with glycosylphosphatidylinositol (GPI)-specific phospholipase C; and (c). inhibition of plasminogen binding by using epsilon-aminocaproic acid. RESULTS: TSP-I up-regulated uPAR and uPA expression 3- and 4-fold, respectively. TSP-1 up-regulated KB tumor cell invasion 5-fold. Inhibition of uPAR blocked the TSP-1-mediated up-regulation of KB tumor cell invasion. CONCLUSIONS: Our data support a central role for TSP-1 in the regulation of uPAR and tumor cell invasion in squamous cell carcinomas of the head and neck cells. Furthermore, uPAR seems to play a crucial role in TSP-1-mediated squamous cell carcinoma of the head and neck tumor cell invasion.

Carcinoma, Squamous Cell↗
PubMed2001

Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an alternative to axillary dissection for many breast cancer patients. Cases of anaphylactic reaction to the isosulfan blue dye used during SLNB have recently been reported. No study on the incidence of serious anaphylactic reactions during SLNB for breast cancer has been reported. METHODS: We reviewed 639 consecutive SLNBs for breast cancer performed at our institution. Sentinel lymph node biopsy was performed using both isosulfan blue dye and technetium-99m sulfur colloid. Cases of anaphylaxis were reviewed in detail. RESULTS: Overall, 1.1% of patients had severe anaphylactic reactions to isosulfan blue requiring vigorous resuscitation. No deaths or permanent disability occurred. In patients with anaphylaxis, hospital stay was prolonged by a mean of 1.6 days. In 1 patient, the anaphylactic reaction required termination of the operation. CONCLUSIONS: Prompt recognition and aggressive treatment of anaphylactic reactions to isosulfan blue are critical to prevent an adverse outcome. Lymphatic mapping with blue dye should be performed in a setting where personnel are trained to recognize and treat anaphylaxis.

Aged↗
PubMed2000

Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor.

We have previously shown that platelet-produced thrombospondin-1 up-regulates the urokinase plasminogen activator and its receptor and promotes tumour cell invasion. Although tumour cells produce thrombospondin-1 in vivo, they produce only minimal amounts of thrombospondin-1 in vitro. To determine the effect of tumour cell-produced thrombospondin-1 in the regulation of the plasminogen/plasmin system and tumour cell invasion, we studied THBS-1-transfected MDA-MB-435 breast cancer cells that overexpress thrombospondin-1. The role of urokinase plasminogen receptor in thrombospondin-1-mediated adhesion and invasion was studied by antisense inhibition, enzymatic cleavage and antibody neutralization. Tumour cell adhesion to collagen and laminin was evaluated. Tumour cell invasion was studied in a modified Boyden chamber collagen invasion assay. Tumour cell thrombospondin-1 induced a 2-7 fold increase in urokinase plasminogen activator receptor and cell-associated urokinase plasminogen activator expression and a 50-65% increase in cell-associated urokinase plasminogen activator and plasmin activities. Furthermore, tumour cell thrombospondin-1 promoted tumour cell invasion and decreased tumour cell adhesion through up-regulation of urokinase plasminogen activator receptor-controlled urokinase plasminogen activator and plasmin activities. We conclude that tumour cell-produced thrombospondin-1 may play a critical role in the regulation of tumour cell adhesion and tumour cell invasion.

Blotting, Western↗
PubMed1999

Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2.

The precise role of TGF-beta in colorectal carcinogenesis is not clear. The purpose of this study was to determine the phenotypic alterations caused by chronic exposure to TGF-beta in non-transformed intestinal epithelial (RIE-1) cells. Growth of RIE-1 cells was inhibited by >75% following TGF-beta1 treatment for 7 days, after which the cells resumed a normal growth despite the presence of TGF-beta1. These 'TGF-beta-resistant' cells (RIE-Tr) were continuously exposed to TGF-beta for >50 days. Unlike the parental RIE cells, RIE-Tr cells lost contact inhibition, formed foci in culture, grew in soft agarose. RIE-Tr cells demonstrated TGF-beta-dependent invasive potential in an in vitro assay and were resistant to Matrigel and Na-butyrate-induced apoptosis. The RIE-Tr cells were also tumorigenic in nude mice. The transformed phenotype of RIE-Tr cells was associated with a 95% decrease in the level of the type II TGF-beta receptor (TbetaRII) protein, a 40-fold increase in cyclooxygenase-2 (COX-2) protein, and 5.9-fold increase in the production of prostacyclin. Most RIE-Tr subclones that expressed low levels of TbetaRII and high levels of COX-2 were tumorigenic. Those subclones that express abundant TbetaRII and low levels of COX-2 were not tumorigenic in nude mice. A selective COX-2 inhibitor inhibited RIE-Tr cell growth in culture and tumor growth in nude mice. The reduced expression of TbetaRII, increased expression of COX-2, and the ability to form colonies in Matrigel were all reversible upon withdrawal of exogenous TGF-beta1 for the RIE-Tr cells.

Animals↗
PubMed1999

Role of urokinase plasminogen activator receptor in thrombospondin 1-mediated tumor cell invasion.

We previously showed that thrombospondin 1 (TSP-1) upregulates the plasminogen/plasmin system and promotes breast tumor cell invasion. Preliminary data from our laboratory using neutralizing antibodies suggested that the upregulation in breast tumor cell invasion seen in response to TSP-1 involved the urokinase plasminogen activator receptor (uPAR). To confirm these findings in MDA-MB-231 breast cancer cells, we developed three other strategies to study the role of uPAR in tumor cell adhesion and TSP-1-mediated tumor cell invasion: (a) enzymatic cleavage of uPAR with glycosylphosphatidylinositol-specific phospholipase C; (b) inhibition at the mRNA level with a uPAR antisense construct (cells named LKAS-MDA); (c) inhibition of plasminogen binding with the lysine analogue epsilon-aminocaproic acid. Adhesion to laminin and type I and type IV collagen with and without the addition of epsilon-aminocaproic acid was studied. Tumor cell invasion was studied in a modified Boyden chamber collagen invasion assay. Antisense uPAR inhibition decreased uPAR expression by 48-66% and cell-associated urokinase plasminogen activator (uPA) by 30-68%. Additionally, antisense uPAR inhibition induced a 68-70% reduction in uPA and plasmin activities. Antisense uPAR transfection increased tumor cell adhesion by 46-53%. A similar effect was observed in epsilon-aminocaproic acid-treated MDA-MB-231 cells. TSP-1-mediated tumor cell invasion was almost completely inhibited by either antisense uPAR inhibition or treatment with phospholipase C or epsilon-aminocaproic acid. We conclude that uPAR plays a crucial role in the regulation of tumor cell adhesion and TSP-1-mediated tumor cell invasion.

Antisense Elements (Genetics)↗
PubMed1999

Cyclooxygenase-2 alters transforming growth factor-beta 1 response during intestinal tumorigenesis.

BACKGROUND: Recent investigation suggests that cyclooxygenase-2 plays an important role in colorectal carcinogenesis. Transforming growth factor-beta1 (TGF-beta 1) is one of the most potent stimulators of cyclooxygenase-2 expression. A key step in intestinal tumorigenesis involves alteration of the normal cellular response to TGF-beta 1. We have hypothesized that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-beta 1. METHODS: RIE-1 cells were stably transfected with rat cyclooxygenase-2 complementary DNA in either the sense (RIE-S) or antisense (RIE-AS) orientation. Tumor cell invasion was assessed with a modified Boyden collagen type I invasion assay in the presence of TGF-beta 1, antibody to urokinase plasminogen activator (uPA), or the selective cyclooxygenase-2 inhibitor SC-58125. Expression of uPA, uPA receptor, and plasminogen activator inhibitor-1 were determined by Western blot and enzyme-linked immunosorbent assay. RESULTS: RIE-1 and RIE-AS did not invade although RIE-S cells were minimally invasive at baseline. TGF-beta 1 had no effect on RIE-1 or RIE-AS invasion; however, TGF-beta 1 significantly upregulated RIE-S cell invasion. All 3 RIE cell lines produce minimal uPA under basal conditions. TGF-beta 1 upregulated uPA production only in the RIE-S cells. Both antibody to uPA and SC-58125 reversed TGF-beta-mediated RIE-S cell invasion. SC-58125 inhibited TGF-beta-mediated RIE-S uPA production. CONCLUSIONS: These results demonstrate that overexpression of cyclooxygenase-2 alters intestinal epithelial response to TGF-beta 1, which may be a mechanism by which cyclooxygenase-2 promotes colon carcinogenesis.

Animals↗
PubMed1998

The effect of thrombospondin-1 and TGF-beta 1 on pancreatic cancer cell invasion.

We have previously shown that thrombospondin-1 (TSP-1) and TGF-beta 1 upregulate the urokinase plasminogen activator (uPA) and its receptor (uPAR) and promote tumor cell invasion in breast cancer. To date, the effect of TSP-1 and TGF-beta 1 on the plasminogen/plasmin system in gastrointestinal epithelial malignancies has not been investigated. In this study, we determined the effect of TSP-1 and TGF-beta 1 on uPA and uPAR expression and on tumor cell invasion in pancreatic cancer. ASPC1 human pancreatic adenocarcinoma cells were incubated for 48 h on cell-conditioned media (CCM) either alone (Control) or with the addition of either TSP-1 (40 micrograms/ml) or TGF-beta 1 (5 ng/ml). uPA and uPAR expression were determined by ELISA. ASPC1 cell invasion was determined in a modified Boyden chamber type I collagen invasion assay. The upper chamber was treated with CCM either alone (Control) or with the addition of anti-uPA (10 micrograms/ml) or anti-uPAR (10 micrograms/ml). The lower chamber was treated with CCM either alone (Control) or with the addition of either TSP-1 (40 micrograms/ml) or TGF-beta 1 (5 ng/ml). TSP-1 and TGF-beta 1 induced a twofold increase on uPAR expression but only a slight increase on total uPA. Tumor cell invasion was upregulated 3.5 to 4.5-fold by TSP-1 and TGF-beta 1, respectively. Anti-uPA and anti-uPAR antibodies completely blocked the TSP-1 and TGF-beta 1-mediated pancreatic tumor cell invasion. We conclude that TSP-1 and TGF-beta 1 mediate pancreatic tumor cell invasion through upregulation of the plasminogen/plasmin system.

Adenocarcinoma↗
PubMed1998

Angiostatin generation by human pancreatic cancer.

BACKGROUND: Angiostatin, a proteolytic fragment of plasminogen, is a potent inhibitor of angiogenesis. In vitro, angiostatin can be generated by pancreatic elastase proteolysis of plasminogen; however, in vivo, the enzymes responsible for angiostatin production are not known. A recent study demonstrates the involvement of a serine protease in angiostatin generation. In this study we sought to determine if the human pancreatic carcinoma cell line ASPC1 produced enzymatic activity capable of converting plasminogen to angiostatin and to determine if urokinase plasminogen activator (uPA) is involved in this system. Methods. ASPC1 cells were grown to near confluence in 20% FBS-RPMI. Media were changed to serum free and cells cultured for an additional 24 h. The serum free conditioned media (SFCM) was obtained. Angiostatin generation was determined by incubating 20 microg of human plasminogen with 100 microl of SFCM for 0, 3, 8, 12, 24, and 48 h. Plasminogen cleavage was assessed in the presence of the following protease inhibitors: pefabloc, aprotinin, phosphoramidon, leupeptin, and EDTA. The effect of uPA on angiostatin generation was determined by incubating plasminogen with antibody to uPA. Angiostatin generation was determined by Western blot. RESULTS: Incubation of plasminogen with SFCM resulted in the generation of immunoreactive bands at 48 kDa corresponding to human angiostatin. Angiostatin generation by ASPC1 SFCM was time dependent; there was a significant decrease in the plasminogen substrate beginning at 3 h with complete conversion to angiostatin by 48 h. Enzymatic activity leading to angiostatin production was found to be due to a serine protease. Antibody to uPA effectively blocked angiostatin production by ASPC1 SFCM in a dose-dependent manner. CONCLUSION: Human pancreatic cancer cells express enzymatic activity which leads to the generation of angiostatin. Conversion of plasminogen to angiostatin is due to a serine protease. This serine protease is most likely uPA.

Angiostatins↗
PubMed1998

Thrombospondin-1 and its CSVTCG-specific receptor in wound healing and cancer.

Growth factors play a crucial role in the regulation of cellular proliferation and matrix degradation in wound healing and cancer. We have shown that thrombospondin 1 (TSP-1) and its cysteine-serine-valine-threonine-cysteine-glycine (CSVTCG)-specific receptor play a key role in cell invasion and matrix degradation in different carcinomas. The present study was done to determine whether TSP-1 and its receptor show a similar pattern of expression in wound healing and cancer. Expression and localization of TSP-1 and its receptor were determined in fetal wounds, adult burn wounds, and different human malignancies by immunohistochemical staining and computerized image analysis. In healing wounds, TSP-1 was expressed in the stroma early in the process, followed by a steep decline. The TSP-1 receptor localized to neovessels and highly proliferating cells (i.e., fibroblasts, basal cells), its levels remaining relatively constant. Cancer cells and tumor-associated microvessels expressed the TSP-1 receptor, whereas TSP-1 localized predominantly to the tumor-associated stroma. These data suggest a critical role for TSP-1 and its CSVTCG-specific receptor in wound healing and cancer.

Adult↗
PubMed1998

Transforming growth factor-beta 1 inhibits generation of angiostatin by human pancreatic cancer cells.

BACKGROUND: Angiostatin, a proteolytic fragment of plasminogen, is a potent inhibitor of angiogenesis. We have previously shown that the human pancreatic cancer cell line ASPC-1 produces enzymatic activity capable of generating angiostatin. In this study we sought to determine whether angiostatin production by ASPC-1 cells was regulated by the growth factor transforming growth factor-beta 1 (TGF-beta 1), a key mediator of tumor angiogenesis. METHODS: ASPC-1 cells were grown to 70% to 80% confluence in 20% fetal calf serum-RPMI. Medium was changed to serum free. TGF-beta 1 was added at concentrations of 0, 1, 5, and 10 ng/mL with or without plasminogen activator inhibitor type-1 (PAI-1) at concentrations of 0, 5, 10, 50, and 100 micrograms/mL. Cells were then cultured for an additional 24 hours. The serum-free conditioned medium was obtained. Angiostatin generation was determined by incubating 20 micrograms of plasminogen with 100 microL of serum-free conditioned medium for 0, 1, 2, 3, 6, 12, and 24 hours. Samples were run on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred. The membrane was probed with a monoclonal antibody to the kringle 1-3 fragment of plasminogen and developed using enhanced chemiluminescence. RESULTS: TGF-beta 1 and PAI-1 inhibited the conversion of plasminogen into angiostatin in a time- and dose-dependent manner. Antibody to PAI-1 completely blocks TGF-beta 1 mediated angiostatin inhibition. CONCLUSIONS: TGF-beta 1 inhibits the generation of the antiangiogenic molecule angiostatin by human pancreatic cancer cells in a time- and dose-dependent manner. This effect is mediated through modulation of the plasminogen/plasmin system.

Adenocarcinoma↗
PubMed1997

Thrombospondin-1 and transforming growth factor-beta l promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system.

BACKGROUND: Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-beta 1 (TGF-beta 1), up-regulates the main plasminogen activator, the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP-1 and TGF-beta 1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. METHODS: The effect of TSP-1 and TGF-beta 1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin system in breast tumor cell invasion were studied with a Boyden Chamber assay. RESULTS: uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-beta 1. The effect of TSP-1 involved its receptor and the activation of TGF-beta 1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-beta 1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP-1- and TGF-beta 1-promoted breast tumor cell invasion. CONCLUSIONS: TSP-1, through the activation of endogenous TGF-beta 1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells.

Breast Neoplasms↗
PubMed1996

Modulation of cranial bone healing with a heparin-like dextran derivative.

Substituted dextran polymers have been shown to bind growth factors and protect them from enzymatic degradation. Using this information, other researchers have been able to use these substituted dextrans to enhance the healing of bone in an environment where bone would otherwise not regenerate. We used substituted dextran polymers to evaluate their ability to accelerate the healing of cranial bone in a rabbit model. We were able to document a more rapid rate of healing and demonstrate micrographic evidence to support that conclusion. Possible mechanisms are postulated.

Analysis of Variance↗
PubMed1995

Thrombospondin and transforming growth factor-beta 1 increase expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in human MDA-MB-231 breast cancer cells.

BACKGROUND: Thrombospondin is a high molecular weight adhesive glycoprotein that has been shown to function in mechanisms of tumor progression. The authors' previous studies have shown that thrombospondin promotes human lung carcinoma invasion by up-regulation of the plasminogen activator system through a mechanism involving the activation of transforming growth factor-beta 1 (TGF-beta 1). In this study, a similar thrombospondin-mediated mechanism operative in breast carcinoma cells is described. METHODS: The effect of thrombospondin and TGF-beta 1 on the capacity of a line of breast carcinoma cells to activate plasminogen was measured as well as the physiologic consequences of these activities on cell adhesion and proliferation. Plasminogen activation was assessed by measuring the plasmin activity and plasminogen activator inhibitor-1 (PAI-1) levels in cell-conditioned media and the cell-associated urokinase-type plasminogen activator (uPA) levels. RESULTS: Treatment of MDA-MB-231 breast carcinoma cells with either thrombospondin or TGF-beta 1 caused increased secretion of PAI-1 with a concomitant decrease in plasmin activity, whereas cell-associated uPA expression was increased with respect to controls. Thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) stimulated the cells to secrete 5.5- and 6.7-fold more PAI-1 than controls, respectively, and caused decreased plasmin activity in the cell culture medium. Conversely, either thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) caused the cells to express 4.55- and 5.38-fold more uPA than controls, respectively. Thrombospondin and TGF-beta 1 induced a more flattened and spread appearance in the cells with no effect on proliferation. These effects could be reversed with antibodies to either thrombospondin or TGF-beta 1 and were not due to contamination of thrombospondin with active TGF-beta 1. CONCLUSIONS: Thrombospondin and TGF-beta 1 function similarly to increase cell-associated uPA and cell-secreted PAI-1. These data suggest that thrombospondin may not only function as an adhesive molecule, but through a mechanism involving the activation of TGF-beta 1, may modulate cell surface protease expression. In addition, these observations suggest that thrombospondin and TGF-beta 1 could promote metastasis by increasing uPA-mediated cell invasion, whereas through the action of PAI-1, also protect blood-born tumor emboli from destruction by host fibrinolytic enzymes.

Breast Neoplasms↗
PubMed1994

Thrombospondin (TSP) and transforming growth factor beta 1 (TGF-beta) promote human A549 lung carcinoma cell plasminogen activator inhibitor type 1 (PAI-1) production and stimulate tumor cell attachment in vitro.

A growing body of evidence has recently implicated TSP and TGF-beta in the process of malignancy, such as tumor cell proliferation, tumor angiogenesis, and metastasis. The purpose of the present study was to evaluate potential mechanisms of TSP and TGF-beta in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-beta promoted tumor cell attachment and spreading in the presence of plasminogen. The mechanism for these effects appeared to be due, in part, to the capacity of TSP and TGF-beta to induce tumor cell production of (PAI-1). PAI-1, which is a natural inhibitor of tumor-cell associated urokinase-type plasminogen activator (uPA) activity, inhibited activation of plasminogen to plasmin in the growth media, thereby preventing plasmin-induced detachment of cells. The TSP-promoted production of PAI-1 could be inhibited not only by anti-TSP antibodies but also by a neutralizing antibody against TGF-beta. These results suggest that TSP by a mechanism involving TGF-beta can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor-associated production of PAI-1.

Adenocarcinoma↗
PubMed1994

Computer-assisted image analysis of tumor sections for a new thrombospondin receptor.

BACKGROUND: A cell surface receptor (50 kd) has been recently identified in malignant cells that recognizes the tumor cell adhesive domain (ie, cysteine-serine-valine-threonine-cysteine-glycine [CSVTCG]) of thrombospondin (TSP). This CSVTCG-specific TSP receptor can be considered as a new tumor marker, and its concentration on the cell surface may correlate directly with the capacity of tumor cells to invade and metastasize. MATERIALS AND METHODS: Six patients with primary, stages III and IV squamous cell carcinomas of the head and neck were studied. Tumor sections were specifically stained for this receptor with immunohistochemical techniques. The stained specimens were then subjected to computer-assisted image analysis. The area of positive staining and the heterogeneity of the pattern of staining were compared to peritumoral angiogenesis and clinical outcome of the patients. RESULTS: The results indicate that those patients with a high and homogenous positive stain score (mean +/- standard error [SE] 78 +/- 5%) for the CSVTCG-specific TSP receptor had high microvessel density and died from metastatic disease within 12 months of initial treatment (correlation coefficients = 0.95 and 1, respectively). Patients with a low and heterogenous positive stain score for receptor (mean +/- SE 8 +/- 2%; P < 0.001) had low microvessel counts and remained disease-free for at least 2 years. There was no relationship between receptor density and histologic classification of the primary tumors. CONCLUSION: The CSVTCG-specific TSP receptor, quantified through image analysis of immunohistochemical stained tissue sections, is highly predictive of clinical outcome in patients with squamous cell carcinomas of the head and neck.

Adult↗
PubMed1994

The relationship of angiogenesis to biological activity in human squamous cell carcinomas of the head and neck.

Tumor angiogenesis has recently been related to tumor growth and metastasis, which determine the clinical outcome of the patient. This study was designed to determine the relationship between angiogenesis in primary squamous cell carcinomas (SCC) of the head and neck and the development of recurrent or metastatic disease, or both. Different SCC of the head and neck were studied. Microvessels were selectively stained using a monoclonal antibody for factor VIII. Microvessel counts were performed in the tumor, in the tissues immediately adjacent, and in normal tissues of similar topographies. Microvessel counts were then correlated with clinical outcome (development of recurrent or metastatic disease, or both). Recurrent or metastatic disease, or both, developed in patients with high microvessel counts (mean, 121.25) in the tissues adjacent to the tumor 7 to 16 months after initial treatment. Those with low microvessel counts (mean, 33.75) were disease-free for 16 months to 6 years (p < 0.01). Microvessel counts inside the tumor were also higher in those in whom recurrences or metastasis, or both, developed, but were not statistically significant. In this study, angiogenesis was directly related to clinical outcome. Thus, angiogenesis may be an independent predictor of recurrent or metastatic disease, or both, which could help in the selection of patients with SCC of the head and neck for aggressive therapy.

Carcinoma, Squamous Cell↗
PubMed1993

Measuring and predicting the performances of practicing physicians: an overview of two decades of research at the University of Utah.

This paper presents the major findings of research carried out by a team of investigators at the University of Utah School of Medicine in the 1960s and 1970s (1) to better understand the multidimensional and complex aspects of practicing physicians' performances, and (2) to investigate relationships between assessments of students in medical school and physicians' performances. The major research began in the 1960s, and data were assembled from a variety of sources to identify factors of physicians' performances. The original study sampled 507 practicing physicians, classified into four highly diverse and representative groups. The team also investigated to what degree these physicians' medical school performances (measured by grades) were predictors of their practice performances. Factor analysis of the data on the physicians' performances resulted in the identification of 25 to 29 factors within each of the four groups. A representative profile of the performances of each physician studied showed how well the physician performed on each of the factors appropriate to his or her specialty and background. Correlation analysis demonstrated that these physicians' performances in medical school, as measured by grade-point averages (GPAs), were almost completely independent of their later performances in their practices, a disturbing finding and one that the team maintained cannot be dismissed by arguments of "restriction of range." In the teams' later studies, 61 measures of physicians' performances were correlated to medical school GPAs in the two basic science years and the two clinical science years. No association beyond chance was observed, and nonsignificant relationships held up regardless of the physicians' specialties or years of experience.(ABSTRACT TRUNCATED AT 250 WORDS)

Achievement↗