Biomedical subjects

Arnold D K Hill

Publications and source records attributed to Arnold D K Hill.

At least 19 recordsLinked to original sources

PubMed2007

Lipophilin B: A gene preferentially expressed in breast tissue and upregulated in breast cancer.

Lipophilin B (LPB), which is also known as BU101, is a secretoglobin which exists in vivo as a complex with the mammary-specific protein, mammaglobin A (MGA). The aim of our study was to investigate the expression of LPB in a panel of breast and nonbreast tissues and compare its expression with that of MGA. Using RT-PCR, LPB mRNA was detected in 16/25 (64%) of normal breast specimens, 23/30 (77%) of fibroadenomas, 102/156 (65%) of primary breast cancers and in 8/36 (22%) nonbreast tissues. Levels of expression of LPB mRNA were significantly higher in breast cancers compared to both normal breast tissues (p = 0.02) and nonbreast tissue (p < 0.001). In the primary breast cancers, expression of LPB mRNA was positively correlated with the estrogen receptor (p = 0.045) but inversely related to both tumor grade (p < 0.001) and proliferation rates (p = 0.0345). Compared to MGA, expression of LPB was more sensitive but less specific for breast cancer. Using Western blotting, LPB migrated with an approximate molecular mass of 7-8 kDa, the expected molecular mass of free LPB. Immunohistochemical analysis of breast cancers showed that LPB expression was predominantly confined to the cytoplasm of tumor cells. We conclude that expression of LPB is preferentially but not exclusively restricted to breast tissue. Since LPB was expressed relatively specifically in breast tissue and was significantly upregulated in breast carcinomas, it is a promising candidate biomarker for breast cancer.

Biomarkers, Tumor↗

PubMed2006

CA 15-3 is predictive of response and disease recurrence following treatment in locally advanced breast cancer.

BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and is the most widely used serum marker in breast cancer. METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC. RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

The role of major duct excision and microdochectomy in the detection of breast carcinoma.

BACKGROUND: The association of nipple discharge with breast carcinoma has resulted in numerous women undergoing exploratory surgery to exclude malignancy. The aim of this study was to determine whether pre-operative factors can identify those patients that are most at risk of carcinoma. METHODS: All patients over a 14-year period (1991-2005) who had a microdochectomy or subareolar exploration for the evaluation of nipple discharge were assessed. Patient characteristics, pre-operative imaging and pathological findings were analysed. RESULTS: Of the 211 patients included in this study, 116 patients had pathological (unilateral, uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with pathological discharge and 2.4% (n = 2) of patients with non-pathological discharge were diagnosed with carcinoma. Overall, major duct excision resulted in the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in 39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 111) of patients. In the patients determined to have malignancy, 44% (n = 4) were premenopausal. No patient with a non-bloody discharge in the total population analysed (28%; n = 59/211), or in the population with a pathological discharge (21%; n = 24/116) was found to have carcinoma upon excision. CONCLUSION: Microdochectomy or major duct excision performed for nipple discharge resulted in a low rate of malignancy on excision. Conservative management of non-bloody nipple discharge can be considered in patients with no other clinical or radiological signs of malignancy.

Adult↗

PubMed2006

Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only.

BACKGROUND AND OBJECTIVES: Ductal carcinoma in-situ on core biopsy does not preclude invasive disease within the excision specimen, resulting in the need for further axillary surgery. We sought to identify predictors of invasion when DCIS is present on core biopsy. METHODS: From a database of 895 breast cancer patients, patients with DCIS on core biopsy who had subsequent surgical excision were identified. Their excision pathology and preoperative mammography were correlated with risk of invasion. RESULTS: Patients (93) with a preoperative diagnosis of DCIS on core biopsy were identified. On excision, 31 patients (33%) had invasive carcinoma and 13 patients (14%) had microinvasion. A preoperative finding of calcification only on mammogram was associated with DCIS on excision (P = 0.014), whereas the presence of other mammographic features increased the risk of invasion. Size > or =5 cm on excision pathology was associated with increased risk of invasion (P = 0.002). Forty-eight percent (n = 11/23) of those diagnosed by ultrasound-guided core biopsy had frank invasion on excision compared to 21% (n = 12/57) diagnosed by stereotactic techniques (P = 0.017). CONCLUSION: Mammographic features and tumor size can help predict invasion in patients who have DCIS on core biopsy. Patients who have features other than calcification on mammography or have tumor size > or =5 cm should be considered for a sentinel node biopsy.

Biopsy↗

PubMed2006

A pathologic assessment of adequate margin status in breast-conserving therapy.

BACKGROUND: The definition of a clear margin in breast-conserving therapy is uncertain. The purpose of this study was to correlate the tumor-margin distance of the excision specimen with the presence of residual tumor at reoperation. We also analyzed predictors of compromised margins and of residual disease. METHODS: All patients who underwent breast-conserving therapy for invasive disease from 1999 to 2003 were reviewed. Pathologic characteristics and the precise tumor distance from the radial margin were recorded. A radial margin was compromised if invasive or (ductal) in situ carcinoma was <5 mm from the margin. RESULTS: Of the 612 patients who underwent breast conservation, 211 (34%) had compromised margins, and 39 had undetermined margins. Of the 161 patients who had a reoperation for compromised margins, 87 (54%) had residual disease. Residual disease after reoperation was present in 58% (56 of 96), 56% (9 of 16), and 45% (22 of 49) of those with tumor-margin distances <1 mm, > or =1 and <2 mm, and > or =2 and <5 mm, respectively. There was a progressive decline in residual disease for each millimeter until a rate of 22% for tumor-margin distances of > or =4 mm and <5 mm was reached. Pathologic size (P = .004), an extensive intraductal component (P = .002), referral from a symptomatic rather than a population-based screening program (P = .02), and the absence of a preoperative diagnosis by core biopsy (P < .0001) were predictive of compromised margins. Only young age (<45 years) was predictive of finding residual disease on reoperation (P = .02). CONCLUSIONS: A total of 45% of patients who had tumor 2 to 5 mm from the radial margin had residual disease on reoperation. Our results support a policy of requiring a 5-mm margin in patients undergoing breast-conserving therapy for invasive disease.

Breast Neoplasms↗

PubMed2006

Identifying patients at risk of compromised margins following breast conservation for lobular carcinoma.

BACKGROUND: The association of invasive lobular carcinoma with high rates of compromised margins in breast conservation makes choice of operation for these patients difficult. We sought to identify patients at risk of compromised margins following breast conservation surgery. METHODS: We reviewed all patients with invasive lobular and invasive ductal carcinoma over a 5-year period (1999-2004). The imaging, pathology and surgical details of patients with invasive lobular carcinoma undergoing breast conservation were analyzed. RESULTS: A total of 991 patients with invasive ductal carcinoma and 150 patients with invasive lobular carcinoma were identified. Lobular carcinomas had a compromised margin rate of 49% (n = 38/77) in breast conservation compared to 24% (n = 143/588) of ductal carcinomas (P < .0001). Mammographic size (P = .017), pathological size (P = .01), age (P = .03), multifocality (P < .0001), and lymphovascular invasion (P = .015) were significantly associated with compromised margins. CONCLUSION: Invasive lobular carcinoma has a 49% rate of compromised margins following breast conservation. Mammographic size greater than 1.5 cm and young age were preoperative factors predictive of compromised margins.

Breast Neoplasms↗

PubMed2006

Needle core biopsy in the diagnosis of phyllodes neoplasm.

BACKGROUND: Accurate identification of phyllodes neoplasms without surgical intervention is difficult, reducing the ability to manage "benign" lumps non-operatively and impacting on the open benign biopsy rate. Needle core biopsy is considered to be a highly accurate technique in the diagnosis of breast carcinoma. Its accuracy in the diagnosis of phyllodes neoplasm has not been established. METHODS: A series of 3729 core biopsies performed between January 1999 and July 2005 were examined. All core biopsies followed by surgical excision were identified. Histologic concordance between core biopsy and excision specimen was analyzed. RESULTS: Twenty-three patients had phyllodes neoplasm on excisional biopsy with prior core biopsy findings as follows: phyllodes neoplasm (n=2), "equivocal" for phyllodes neoplasm (n=12), fibroadenoma (n=3), benign (n=6). The false negative rate for phyllodes neoplasm was therefore 39% (n=9/23). Of the total biopsy series, 35 patients had a core biopsy suggesting the possibility of phyllodes neoplasm. Of these, 32% (n=11) were found to be phyllodes neoplasm on excision, 3% (n=1) phyllodes neoplasm with breast carcinoma, 6% (n=2) breast carcinoma, and 3% (n=1) sarcoma. When a preference for phyllodes neoplasm (n=4) was stated on the equivocal core biopsies, excision correlated with the stated preference; this correlation also occurred in 90% (n=9/10) of core biopsies where fibroadenoma was favored. CONCLUSIONS: Needle core biopsy rarely produces a definite preoperative diagnosis of phyllodes neoplasm. A diagnosis of fibroadenoma or equivocal phyllodes neoplasm on core biopsy should not prevent excision if clinical suspicion remains.

Adult↗

PubMed2006

FDG PET/CT demonstrates the effectiveness of isolated limb infusion for malignant melanoma.

A 43-year-old woman presented with a nodular melanoma treated with wide excision, split skin graft, and sentinel node biopsy. At 2-year follow up, she was noted to have clinical recurrence at the excision site. FDG PET/CT demonstrated in-transit metastasis in her left thigh in addition to disease at the site of the sentinel node biopsy. Isolated limb infusion was performed with melphalan and dactinomycin. PET/CT at 5 weeks demonstrated resolution of the in-transit metastasis and the disease at the excision site. This report of PET/CT demonstrates the effectiveness of chemotherapy for malignant melanoma delivered by isolated limb infusion.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Tamoxifen-induced ER-alpha-SRC-3 interaction in HER2 positive human breast cancer; a possible mechanism for ER isoform specific recurrence.

Differential signalling between the two oestrogen receptor (ER) isoforms in the presence of tamoxifen has been described. We hypothesise that differential recruitment of the steroid receptor co-activator, SRC-3 to ER-alpha and ER-beta may in part explain associations between ER isoforms and response to endocrine treatment. SRC-3 was localised within epithelial cells of breast tumour tissue and was co-localised with ER-alpha and ER-beta, (n=112). Expression of SRC-3 was found to be positively associated with ER-alpha (P=0.0021) and inversely with ER-beta (P<0.0001). Uniquely, this study utilises primary cell cultures derived from patient tumours, thus providing samples not readily available in most molecular model systems. These samples have enabled us to investigate the influence of growth factor pathways on steroid receptor-co-activator interactions. In HER2 (human epidermal growth factor receptor 2) positive primary tumour cell cultures 17beta-estradiol induced a decrease in SRC-3, whereas upregulated SRC-3 expression. Furthermore, treatment with tamoxifen-induced SRC-3 recruitment to the ER-oestrogen response element and enhanced interaction between SRC-3 and ER-alpha, but not ER-beta. Knockdown of SRC-3 results in a concomitant loss of expression of the oestrogen target gene pS2. Furthermore, silencing of SRC-3 resensitizes endocrine resistant, HER2 positive cells to the anti-proliferative effects of tamoxifen. The ability of ER-alpha, but not ER-beta to recruit SRC-3 in the presence of tamoxifen may in part explain the differential ER isoform associations with recurrence in human breast cancer.

Antineoplastic Agents, Hormonal↗

PubMed2006

Growth factor-dependent regulation of survivin by c-myc in human breast cancer.

Survivin has emerged as a unique regulator of cell death through its response to growth factors, such as basic fibroblast growth factor (bFGF), which we have previously shown to be mitogen-activated protein kinase (MAPK) dependent. The transcriptional complex myc/max is an oncogene that lies downstream of the MAPK pathway, suggesting a possible role in survivin's regulation. In this study, we investigated the ability of bFGF to induce signalling of the MAPK effector transcription factor c-myc in human breast cancer. Treatment of SK-BR-3 breast cancer cell line with growth factor induced survivin expression and recruitment of c-myc to its response element in the promoter region of the target gene survivin as demonstrated by electromobility shift analysis and chromatin immunoprecipitation assays. The promoter region of survivin was assessed using bioinformatic techniques and DNA footprinting. Overexpression of c-myc increased survivin protein expression. This effect was eliminated when siRNA against c-myc was transfected into the cells. c-Myc drove transcriptional activity of survivin when transfected into SK-BR-3 cells with a luciferase reporter vector harbouring the c-myc response element specific for survivin. Using confocal fluorescent microscopy, myc was located to the nucleus of breast tumour epithelial cells and was found to be significantly associated with survivin (P < 0.0001). These data provide evidence that growth factors can signal through the transcription factor c-myc in human breast cancer. They also indicate a role for c-myc in the transcriptional regulation of survivin in breast cancer.

Base Sequence↗

PubMed2006

Current status of combined hormone replacement therapy in clinical practice.

Approximately 20 million women worldwide use hormone replacement therapy (HRT). Formerly, it was thought to confer beneficial cardiac protection and reduce osteoporosis in addition to relieving the symptoms of menopause. However, many recent trials have contradicted these beliefs. The risk of breast cancer associated with HRT use has been well documented but underestimated. Many recent trials have reported higher than expected breast cancer incidence rates, particularly associated with combined HRT. Although it was believed estrogen conferred cardiac protection and reduced the incidence of myocardial ischemic events and cerebrovascular accidents, the more recent literature indicates that this is not true and that HRT users have a higher risk of cardiac and cerebral events. The role of HRT in clinical practice has been redefined. It is no longer an acceptable form of treatment for most women. The evidence indicates that the use of long-term HRT is no longer clinically justifiable.

Aged↗

PubMed2005

Electronic learning can facilitate student performance in undergraduate surgical education: a prospective observational study.

BACKGROUND: Our institution recently introduced a novel internet accessible computer aided learning (iCAL) programme to complement existing surgical undergraduate teaching methods. On graduation of the first full cycle of undergraduate students to whom this resource was available we assessed the utility of this new teaching facility. METHOD: The computer programme prospectively records usage of the system on an individual user basis. We evaluated the utilisation of the web-based programme and its impact on class ranking changes from an entry-test evaluation to an exit examination in surgery. RESULTS: 74.4% of students were able to access iCAL from off-campus internet access. The majority of iCAL usage (64.6%) took place during working hours (08:00-18:00) with little usage on the weekend (21.1%). Working hours usage was positively associated with improvement in class rank (P = 0.025, n = 148) but out-of hours usage was not (P = 0.306). Usage during weekdays was associated with improved rank (P = 0.04), whereas weekend usage was not (P = 0.504). There were no significant differences in usage between genders (P = 0.3). Usage of the iCAL system was positively correlated with improvement in class rank from the entry to the exit examination (P = 0.046). Students with lower ranks on entry examination, were found to use the computer system more frequently (P = 0.01). CONCLUSION: Electronic learning complements traditional teaching methods in undergraduate surgical teaching. Its is more frequently used by students achieving lower class ranking with traditional teaching methods, and this usage is associated with improvements in class ranking.

Adult↗

PubMed2005

Mammaglobin a in breast cancer: existence of multiple molecular forms.

Existing serum-based markers for breast cancer all lack organ specificity. Mammaglobin A (MGA) is a 93 amino acid protein expressed almost exclusively in breast tissue. The aim of our study was to investigate the different forms of MGA protein in fibroadenomas and breast carcinomas. MGA protein was measured by Western blotting in 132 breast cancers, 29 fibroadenomas and 14 nonbreast tissues. MGA protein in breast tissue was found to exist in 2 main forms. These forms migrated with approximate molecular masses of 18 and 25 kDa. Both forms of MGA were detected more frequently in breast carcinomas compared to fibroadenomas. The high molecular weight form of MGA but not the low molecular weight form was found more frequently in hormone receptor-positive than in receptor-negative cancers. Furthermore, an inverse relationship was found between the high molecular weight form of MGA and both tumour grade and proliferation index. No significant correlation was found between the MGA proteins and either tumor size or nodal status. Our results show that MGA protein exists in 2 main forms in breast tissue. As the high molecular weight form correlated positively with hormone receptors and negatively with tumor grade and proliferation rate, its presence is likely to be associated with a favourable prognosis for breast cancer. As expression of MGA is almost breast specific, it is a promising marker for breast cancer. Its most immediate use is likely to be in detecting micrometastases from breast cancer.

Biomarkers, Tumor↗

PubMed2005

Associations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast cancer.

PURPOSE: Associations between p160 coactivator proteins and the development of resistance to endocrine treatment have been described. We hypothesized that nuclear receptor coregulatory proteins may interact with nonsteroid receptors. We investigated the mitogen-activated protein kinase-activated transcription factors, Ets, as possible interaction proteins for the coactivators SRC-1 and AIB1 and the corepressor NCoR in human breast cancer. EXPERIMENTAL DESIGN: Expression and coexpression of Ets and the coregulatory proteins was investigated using immunohistochemistry and immunofluorescence in a cohort of breast tumor patients (N = 134). Protein expression, protein-DNA interactions and protein-protein interactions were assessed using Western blot, electromobility shift, and coimmunoprecipitation analysis, respectively. RESULTS: Ets-1 and Ets-2 associated with reduced disease-free survival (P < 0.0292, P < 0.0001, respectively), whereas NCoR was a positive prognostic indicator (P < 0.0297). Up-regulation of Ets-1 protein expression in cell cultures derived from patient tumors in the presence of growth factors associated with tumor grade (P < 0.0013; n = 28). In primary breast tumor cell cultures and in the SKBR3 breast cell line, growth factors induced interaction between Ets and their DNA response element, induced recruitment of coactivators to the transcription factor-DNA complex, and up-regulated protein expression of HER2. Ets-1 and Ets-2 interacted with the coregulators under basal conditions, and growth factors up-regulated Ets-2 interaction with SRC-1 and AIB1. Coexpression of Ets-2 and SRC-1 significantly associated with the rate of recurrence and HER expression, compared with patients who expressed Ets-2 but not SRC-1 (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: These data describe associations and interactions between nonsteroid transcription factors and coregulatory proteins in human breast cancer.

Blotting, Western↗

PubMed2005

Unusual presentation of a giant parathyroid adenoma: report of a case.

Parathyroid adenomas account for most cases of primary hyperparathyroidism (1 degrees HPT). Certain symptoms and biochemical abnormalities alert the surgeon to their presence, since these benign tumors are rarely evident on physical examination. Moreover, because they are usually very small, preoperative localization using sestamibi scanning or ultrasonography is required to avoid bilateral neck exploration. Parathyroid adenomas rarely attain huge proportions. We report a case of a parathyroid adenoma measuring 8 x 5 x 3.5 cm and weighing 110 g; to our knowledge the greatest mass reported in the literature. Interestingly, despite its huge size it did not cause many of the hypercalcemic symptoms usually associated with larger adenomas, but rather it manifested with symptoms of local pressure, another unusual property of this atypical tumor.

Adenoma↗

PubMed2005

The accuracy of ultrasound, stereotactic, and clinical core biopsies in the diagnosis of breast cancer, with an analysis of false-negative cases.

OBJECTIVE: Preoperative core biopsy in breast cancer is becoming the standard of care. The aim of this study was to analyze the various methods of core biopsy with respect to diagnostic accuracy and to examine the management and outcome of those patients with false-negative biopsies. METHODS: All patients undergoing core biopsy for breast abnormalities over a 5-year period (1999-2003) were reviewed. The accuracy rates for each method of core biopsy, the histologic agreement between the core pathology and subsequent excision pathology, and the length of follow-up for cases of benign disease were studied. Patients whose biopsies were benign but who were subsequently diagnosed with cancer underwent detailed review. RESULTS: There were 2427 core biopsies performed over the 5-year period, resulting in a final diagnosis of cancer in 1384 patients, benign disease in 954 patients, and atypical disease in 89 patients. Biopsy type consisted of 1279 ultrasound-guided cores, 739 clinically guided cores, and 409 stereotactic-guided cores. The overall false-negative rate was 6.1%, with specific rates for ultrasound-, clinical-, and stereotactic-guided cores of 1.7%, 13%, and 8.9%, respectively. False-negative biopsies occurred in 85 patients, and in 8 of these patients the diagnosis was delayed by greater than 2 months. In all other false-negative cases, "triple assessment" review allowed prompt recognition of discordant biopsy results and further evaluation. CONCLUSION: Ultrasound guidance should be used to perform core biopsies in evaluating all breast abnormalities visible on ultrasound. Adherence to principles of triple assessment following biopsy allows for early recognition of the majority of false-negative cases.

Adult↗

PubMed2004

High preoperative CA 15-3 concentrations predict adverse outcome in node-negative and node-positive breast cancer: study of 600 patients with histologically confirmed breast cancer.

BACKGROUND: CA 15-3 is the most widely used serum marker in breast cancer. Currently, its main uses are in the surveillance of patients with diagnosed disease and monitoring the treatment of patients with advanced disease. METHODS: Preoperative CA 15-3 concentrations were measured prospectively in 600 patients with histologically confirmed breast cancer. Marker concentrations were related to patient outcome by both univariate and multivariate analysis. RESULTS: After a median follow-up of 6.27 years, patients with high preoperative concentrations of CA 15-3 (>30 units/L) had a significantly shorter overall survival pattern than those with low concentrations. As a prognostic factor, CA 15-3 was independent of tumor size, axillary node status, and patient age. As well as being prognostic in the total population of patients, CA 15-3 also predicted outcome in different subgroups of patients, including those with both node-negative and node-positive disease, those who were both estrogen receptor (ER)-negative and ER-positive, and those younger and older that 50 years of age. CA 15-3 was also predictive of outcome irrespective of the type of adjuvant therapy administered, i.e., whether adjuvant hormone therapy, adjuvant chemotherapy, or radiotherapy was administered. CONCLUSION: Assay of CA 15-3 is a relatively inexpensive, convenient, and noninvasive method for evaluating prognosis in newly diagnosed breast cancer patients.

Adult↗

PubMed2004

Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.

BACKGROUND: Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated. MATERIALS AND METHODS: Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody. RESULTS: Plasma endostatin levels, in breast cancer patients, were significantly elevated (P = 0.015) in the post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76 etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival. CONCLUSIONS: Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.

Adult↗