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Robert E Mansel

Publications and source records attributed to Robert E Mansel.

At least 19 recordsLinked to original sources
PubMed2006

Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin-5 modulation.

Tight junctions (TJs) in endothelial cells act as cell-cell adhesion structures, governing paracellular permeability (PCP). Disruption can lead to leaky vascular bed and potentially to oedema and swelling of tissues, the aetiology of mastalgia. These changes may also cause vascular spread of cancer cells. This study aimed to determine whether the function of TJs in endothelial cells can be strengthened by gamma linolenic acid (GLA), selenium (Se) and iodine (I) in the presence of 17beta-estradiol (17beta-estradiol), which causes leakage of endothelial cells by disruption of TJs in endothelium. GLA, I, and Se individually increased transendothelial resistance. The combination of all three agents also had a significant effect on TER. Addition of GLA/Se/I reduced PCP of the endothelial cells. Treatment with GLA/Se/I reversed the effect of 17beta-estradiol in reducing TER and increasing PCP. Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h there was increasing relocation to endothelial cell-cell junctions of the TJ proteins Claudin-5, Occludin, and ZO-1. Interestingly, this relocation was particularly evident with treatments containing I when probing with Claudin-5 and those containing Se for Occludin. There was a small increase in overall protein levels when examined by Western blotting after treatment with GLA/Se/I when probed with Claudin-5 and Occludin. We report that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells, by way of regulating the distribution of Claudin-5, Occludin, and ZO-1. Interestingly, this combination was also able to completely reverse the effect of 17beta-estradiol in these cells.

Antioxidants↗
PubMed2006

Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.

BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P < .001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P < or = .003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P > .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Arm↗
PubMed2006

Expression of interleukin 11 and its receptor and their prognostic value in human breast cancer.

BACKGROUND: Recent experimental evidence has shown a potential role of interleukin (IL)-11 and its receptor in breast cancer development and progression. However, there is little clinical information to support this hypothesis. We examined the expression of IL-11 and its receptor in primary breast cancer tissue samples and correlated their level of expression with the clinical outcome. METHODS: Primary breast cancer samples (n=109) and matched background tissue obtained from patients in the cohort (n=33) were processed for frozen section and RNA extraction. Frozen sections from matched tissues were immunostained with IL-11 and IL-11 receptor antibodies. Staining intensity was analyzed by computer image analysis. RNA was reverse-transcribed and quantified before analysis by quantitative polymerase chain reaction. Results were expressed as the number of transcripts (standardized by beta-actin). The data were compared with the clinical outcome of the disease. RESULTS: The intensity of staining for both IL-11 and the IL-11 receptor was distinctly high in tumor samples (P<.01). The transcript level of IL-11 was significantly higher in node-positive tumor samples compared with node-negative samples (P=.02). Tumors with a poor prognostic index and poor histological grade showed a higher level of IL-11. A higher level of IL-11 was linked to poorer survival with Kaplan-Meier survival analysis. CONCLUSIONS: IL-11 can be a predictor of poor prognosis in human breast cancer.

Breast Neoplasms↗
PubMed2006

Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer.

15-lipoxygenase (15-LOX) belongs to the structurally and functionally related nonheme iron dioxygenases family. It has two isoforms, type-1 (leukocyte type) and type-2 (epidermis type) and converts arachidonic acid to eicosanoids including the anti-cancer 13-HODE. In the current study, we investigate the expression of both isoforms of 15-LOX in human breast cancer (n=120) and normal mammary tissues (n=32), using immunohistochemistry and quantitative analysis of the gene transcripts. Both 15-LOX-1 and 15-LOX-2 were found in normal mammary epithelial cells and in vascular endothelial cells. The staining of both 15-LOX-1 and 15-LOX-2 was markedly weaker in breast cancer cells. Using quantitative analysis, it was found that the 15-LOX-1 and 15-LOX-2:CK19 ratios were lower in breast tumour tissues, compared with normal tissues (P=0.05 and P=0.035, respectively). Although no significant correlation was seen between either isoforms and nodal status and tumour grade, significantly lower ratio of 15-LOX-2:CK19 was seen in late stage breast tumours. Both 15-LOX-2 and 15-LOX-1 were found to be at significantly lower levels in tumours from patients who developed metastasis (P=0.0018 for 15-LOX-2 and P=0.031 for 15-LOX-1, compared with patients who remained disease free), and in patients who died of breast cancer related causes (P=0.043 and P=0.020 vs disease-free group, for 15-LOX-2 and 15-LOX-1, respectively). It was also demonstrated that ER-positive tumours had significantly lower levels of 15-LOX-2, but not 15-LOX-1, compared with ER-negative tumours (P=0.031). Finally, the study has shown that the 15LOX1:15LOX2 ratio had a strong value in predicting clinical outcome. Patients who developed metastasis, local recurrence and died of breast cancer had significantly lower ratio compared with those who remained disease free (P=0.0057, P=0.0075, P=0.0091, respectively). In conclusion, the current study reports aberrant expression of both isoforms of 15-LOX, 15-LOX-1 and 15-LOX-2, in human breast cancer. The reduction is correlated with the disease progression of breast cancer and a poor clinical outcome. The study has also reported a link between 15-LOX-2 and oestrogen receptor status in breast tumours. Both isoforms of 15-lipoxygenase have a tumour suppressing role in breast cancer.

Arachidonate 15-Lipoxygenase↗
PubMed2006

Is there a role of sentinel lymph node biopsy in ductal carcinoma in situ?: analysis of 587 cases.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in patients with a core needle-biopsy diagnosis of ductal carcinoma in situ (DCIS) has been intensely debated. Core needle-biopsy has an inherent sampling error leading to histologic underestimation of invasive disease. If SLNB is not performed at the time of the definitive operative procedure, patients found to have an invasive cancer, will require a second operative procedure. The study was designed to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify the use of SLNB. METHODS: We identified 587 women with an initial core needle-biopsy diagnosis of DCIS in the prospective Breast Test Wales (BTW) database from 1995 through 2005. A variety of clinical, mammographic and histologic features were identified and correlated with the presence of invasion at excision using univariate and multivariate analyses. RESULTS: Median age of patients at the time of diagnosis was 58 years (range 41 to 83 years). 201 patients (36%) were treated by mastectomy and 354 (64%) by breast conservation surgery. 220 of 587 patients (38%) were found to have invasive disease on final pathology. On univariate analysis, the rate of upstaging was related to the presence of a clinically palpable mass and size of the mass (both p<0.0001, Mann-Whitney test); mammographic presence of a mass and size of the mass (both p<0.0001, Mann-Whitney test). Multivariate logistic regression analysis revealed 2 independent predictors of invasive cancer on final pathology: mass on clinical examination (odds ratio [OR], 5.09; p<0.0001) and mammographic mass (OR, 7.37; p<0.0001). Age, grade of DCIS, microinvasion and presence of comedonecrosis did not help in distinguishing between patients with DCIS and those upstaged to invasive carcinoma at definitive surgery. Axillary nodal staging (four node sampling or clearance) was done at the time of surgery in 269 patients. Axillary nodal metastases were found in 35 of 269 patients (13%). All 35 patients had invasive carcinoma on final pathology. CONCLUSION: The indiscriminate use of SLNB in patients with DCIS seems excessive. Our study suggests that patients with a mass on clinical examination or mammogram have an increased risk of invasive disease at the time of definitive operative procedure and should undergo SLNB at the initial procedure. In addition, SLNB should be performed in patients undergoing mastectomy because mastectomy precludes SLNB if invasive disease is subsequently discovered.

Adult↗
PubMed2006

Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer--results of the ALMANAC validation phase.

BACKGROUND: Despite the widespread application of sentinel lymph node biopsy (SLNB) for early stage breast cancer, there is a wide variation in reported test performance characteristics. A major aim of this prospective multicentre validation study was to quantify detection and false-negative rates of SLNB and evaluate factors influencing them. METHODS: Eight-hundred and fourty-two patients with clinically node-negative breast cancer underwent SLNB according to a standardised protocol that used a combination of radiopharmaceutical 99mTc-albumin colloid and Patent Blue V dye. SLNB was followed by standard axillary treatment at the same operation in all patients. RESULTS: Sentinel lymph nodes (SLNs) were identified in 803 (96.1%) of 836 evaluable cases. The median number of SLNs removed per patient was 2 (range 1-9). There were 19 false negatives, resulting in a sensitivity of 263/282 (93.3%) and accuracy 782/803 (97.6%). SLNs were successfully identified by blue dye in 698 (85.6%), by isotope in 698 (85.6%), and by the combination of blue dye and isotope in 782 (96.0%) of 815 patients. Among 276 node positive patients, one or more positive SLNs were identified by blue dye in 251 (90.9%), by isotope in 246 (89.1%) and by the combination of blue dye and gamma probe in 258 (93.5%). Obesity, tumor location other than upper outer quadrant and non-visualisation of SLNs on the pre-operative lymphoscintiscan were significantly associated with failed localisation (p<0.001, p=0.008, p<0.001, respectively). The false-negative rate in patients with grade 3 tumors was 9.6%, compared with 4.7% in those with grade 2 tumors (p=0.022). The false-negative rate in patients who had one SLN harvested was 10.1%, compared with 1.1% in those who had multiple SLNs (three or more) removed (p=0.010). CONCLUSION: SLNB can accurately determine whether axillary metastases are present in patients with early stage breast cancer with clinically negative axillary nodes. Both success and accuracy of SLNB are optimised by the combined use of blue dye and isotope. SLNB success decreases with increasing body mass, tumor location other than the upper outer quadrant and non-visualisation of hot nodes on the pre-operative lymphoscintiscan. This study demonstrates reduction in the predictive value of a negative SLNB in grade 3 tumors.

Adult↗
PubMed2006

Angiomotin and angiomotin like proteins, their expression and correlation with angiogenesis and clinical outcome in human breast cancer.

BACKGROUND: Angiomotin is a newly discovered molecule that regulates the migration and tubule formation of endothelial cells. It therefore has been implicated in the control of angiogenesis under physiological and pathological conditions. This study examined the expression of angiomotin and its analogues, angiomotin-like 1 (L1) and -like 2 (L2) in breast tumour tissues, and analysed their correlation with angiogenesis and clinical outcomes. METHODS: Human breast tissues (normal n = 32 and tumours n = 120) were used. The levels of expression of angiomotin, L1 and L2 were determined using reverse transcription PCR. Microvessels were stained using antibodies against PECAM, von Willebrand factor (factor 8, or vWF) and VE-cadherin. The transcript levels of angiomotin and its analogues were assessed against the clinical and pathological background, including long term survival (120 months). RESULTS: Breast cancer tissues expressed significantly higher levels of angiomotin transcript, compared with normal mammary tissues (33.1 +/- 11 in normal versus 86.5 +/- 13.7 in tumour tissues, p = 0.003). Both L1 and L2 were seen at marginally higher levels in tumour than normal tissues but the difference was not statistically significant. Levels of angiomotin were at significantly higher levels in grade 2 and grade 3 tumours compared with grade 1 (p < 0.01 and p = 0.05 respectively). The levels of angiomotin in tumours from patients who had metastatic disease were also significantly higher than those patients who remained disease free (p = 0.03). Multivariate analysis indicated that angiomotin transcript was an independent prognostic factor (p = 0.031). No significant correlations were seen between angiomotin-L1 and L2 with the clinical outcome. Furthermore, high levels of angiomotin transcript were associated with shorter overall survival (p < 0.05). There was a high degree of correlation between levels of vW factor and that of angiomotin (p < 0.05), but not angiomotin-L1 and angiomotin-L2. CONCLUSION: Angiomotin, a putative endothelial motility factor, is highly expressed in human breast tumour tissues and linked to angiogenesis. It links to the aggressive nature of breast tumours and the long term survival of the patients. These data point angiomotin as being a potential therapeutic target.

Angiomotins↗
PubMed2006

Metastatic cutaneous Crohn's disease of the nipple: report of a case.

A case of cutaneous Crohn's disease involving the right breast and presenting as multiple periareolar fistulas in a 46-year-old female is reported. The lesion had initially been diagnosed and treated as a simple abscess. She had a 26-year history of Crohn's disease with numerous hospitalizations for bowel resections and control of diarrhea. Histopathologic examination following excision of the fistulas and total duct excision, however, showed well-defined granulomas containing multinucleated giant cells characteristic of extraintestinal Crohn's disease.

Breast Diseases↗
PubMed2006

Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells.

MT1-MMP (membrane type-1 matrix metalloproteinase), otherwise known as MMP14 is a proteolytic enzyme known to be involved in degradating extracellular matrix and assist progression of cancer invasion and progression. We investigated the impact of targeting the expression of MT1-MMP in breast cancer and its clinical relevance. Human breast cancer cell line MDA-MB-231 was used. Expression of MT1-MMP in the breast cancer cell line was manipulated by way of retroviral ribozyme transgene. The in vitro invasion, growth and cell migration were determined on cell lines transfected with either the transgene or control plasmid. Protein and message levels of MMP14 was also assessed using immunohistochemistry and real-time quantitative analysis, and correlated with clinical and pathological information of the patients. Retroviral ribozyme transgene to human MT1-MMP successfully knocked down the levels of MT1-MMP mRNA from MDA-MB-231 cells. Reduction of MT1-MMP from the breast cancer cells resulted in significant reduction of in vitro invasiveness and loss of response to an invasion stimulus, HGF, compared with control and wild-type cells. The invasion index for MT1-MMP knockdown cells were 13+/-3.1 (without HGF) and 16.4+/-2.3 (with HGF, p=0.14), and the index for transfection control cells 25.3+/-4.3 (without HGF) and 40.4+/-4.1 (with HGF, p=0.0049). Transfection with the transgenes did not change the rate of cell growth. In clinical breast cancer, MT1-MMP staining was both membranous and cytoplasmic. Tumour cells displayed stronger staining compared with normal mammary epithelial cells. Tumour tissues had a marginally higher levels of the MMP14 transcript (8.6+/-1.9), compared with normal tissues (4.7+/-1.4), p=0.13. No significant difference was observed between node positive and node negative tumours (9.0+/-2.2 vs 8.7+/-3.1, p=0.24). Marginally higher levels of the MMP14 transcript were seen in tumours which developed metastasis and local recurrence. However, tumours from patients who died of breast cancer related causes had significantly higher levels of the transcript, compared with tumours from patients who remained disease-free 10 years after initial surgery (12.2+/-2.5 vs 6.3+/-1.2, p=0.0091). MT1-MMP is a proteolytic enzyme that is pivotal in controlling the invasiveness of breast cancer cells. It is highly expressed in aggressive breast tumours and is associated with clinical outcome. The enzyme is a potential therapeutic target in breast cancer.

Breast Neoplasms↗
PubMed2006

Expression of pigment epithelial derived factor is reduced in non-small cell lung cancer and is linked to clinical outcome.

Angiogenesis is under the exquisite control of a network of angiogenic factors and anti-angiogenic factors. PEDF (pigment epithelial derived factor) is one of the known anti-angiogenesis factors and is naturally occurring in the body. There has been studies to show that the factor plays an important role in negating the angiogenic process in pathological conditions in the eye. However, little is known about its expression in solid tumors. The current study examined PEDF expression at protein and message levels and investigated its critical link with cancer progression and prognosis in patients with non-small cell lung cancer (NSCLC). We used immunohistochemistry to examine the protein expression of PEDF and to evaluate the microvessel density (MVD) in a cohort of 91 NSCLC patients. In addition, real-time quantitative PCR was used to measure levels of the PEDF transcript. PEDF was positively stained in cytoplasm of cancer cells, but at a lower level, compared with normal cells in the lung tissues. Low levels of PEDF were seen in 57.1% patients. The levels of PEDF appeared to be associated with MVD, in that patients with reduced PEDF had a significantly high MVD count (28.50), compared with patients with high levels of PEDF who had a 16.98 MVD count (p<0.0005). In univariate but not multivariate analysis PEDF was an independent prognostic factor. In real-time PCR analysis, PEDF mRNA level of cancer tissue was significantly lower than normal tissue (0.55+/-0.36 vs 0.72+/-0.26, p=0.024, paired t-test). PEDF mRNA level in cancer tissue was negatively associated with TNM stage and the tumor size (p<0.05, independent t-test). Finally, low levels of PEDF in lung tumor tissues was associated with a significantly shorter survival (p=0.038) using Kaplan-Meier and Cox analyses. In this first study, PEDF was reduced at both protein and mRNA level in NSCLC tumors compared with normal lung tissues. This reduction is associated with an increase in microvessel density in tumors and significantly associated with TNM stage, tumor size and the overall survival. PEDF is an important factor in NSCLC development and may be a of prognostic value for NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Expression of breast cancer specific gene-1 (BCSG-1/gamma-synuclein) is associated with tumour grade but not with clinical outcome of patients with breast cancer.

This study examined the expression and distribution of BCSG-1 in human breast cancer tissue. IHC revealed that BCSG-1 was primarily seen as a cytosolic protein, weakly staining normal mammary epithelial cells but increased in breast tumour cells. Q-PCR revealed that node negative and positive tumours had similar levels of BCSG-1 transcript and BCSG-1/CK19 ratio. There were significantly higher levels in grade 2 and grade 3 tumours compared to grade 1. Patients with NPI (Nottingham prognostic indicator) < 3.4, had a predicted 80% 15-year survival. After a 10-year follow-up, no significant difference was seen between tumours from patients remaining disease-free and those who died of breast cancer. The levels of BCSG-1 significantly correlated with an associated molecule, transglutaminase-3 (r = 0.307, P < 0.05), and weakly with transglutaminase-7 (r = 0.183). BCSG-1 is increased in breast tumour cells, is negatively associated with tumour grade and significantly correlates with levels of transglutaminase-3.

Breast Neoplasms↗
PubMed2006

Elevated levels of tumour endothelial marker-8 in human breast cancer and its clinical significance.

Tumour endothelial marker-8 (TEM-8) belongs to a family of endothelial markers that are raised during tumour angiogenesis. We have recently reported aberrant expression of TEMs at the mRNA level in human breast cancer. This study sought to examine the level of TEM-8 expression at the protein and mRNA level in human breast cancer tissue, and in a panel of human breast cancer cell lines. We also wished to determine if TEM-8 can be used as a suitable marker for identifying tumour associated micro-vessels. At the mRNA level more tumours showed positive TEM-8 expression compared to normal background tissue. TEM-8 was detected in a variety of breast cancer cell lines, endothelial cells (HECV) and in a human fibroblast cell line (MRC5) at both the mRNA and protein level. Using immunohistochemistry the distribution of TEM-8 staining was more widespread in invasive breast cancer tissue compared to normal background tissue. Furthermore, the TEM-8 marker was found to be more discriminatory in identifying micro-vessels in tumour endothelium (2.8+/-0.83 vs. normal 1.66+/-0.52; P<0.011), compared to the vWFA marker (1.61+/-0.54 vs. normal 2.71+/-0.76; P<0.009). Raised levels of TEM-8 were associated with shorter survival outcome, but were not correlated to disease-free survival as shown by Kaplan-Meier and Cox regression analysis. We conclude that TEM-8 is a useful marker for identifying tumour associated micro-vessels and that elevated levels are associated with disease progression, which may have some bearing on the prognostic outcome in breast cancer.

Biomarkers, Tumor↗
PubMed2005

Aberrant expression of 5-lipoxygenase-activating protein (5-LOXAP) has prognostic and survival significance in patients with breast cancer.

5-lipoxygenase (5-LOX)-activating protein, 5-LOXAP also known as LOX5AP or FLAP, is a protein that works closely with 5-LOX in regulating the metabolism of arachidonate. Some of the eicosanoid products of 5-LOX/5-LOXAP are known to play active roles in the function of cancer cells, including breast cancer cells. The current study investigated the expression of 5-LOXAP in clinical breast cancer and the prognostic impact of 5-LOXAP and 5-LOX in patients with breast cancer. A cohort of breast tumour tissues (n = 122) with normal background tissues (n = 32) were investigated. 5-LOXAP and 5-LOX transcripts were determined using RT-PCR and quantitative RT-PCR. Levels of the transcripts were analysed against clinical and pathological information. Breast tumour tissues had significantly higher levels of 5-LOX transcript compared with normal tissues (P = 0.015). The transcript was seen at significantly higher levels in node positive tumours than that in node negative tumours (P = 0.02). The prognostic significance was assessed using both a prognostic index and clinical outcome. Value of 5-LOXAP was first demonstrated when using the Nottingham Prognostic Index (NPI) as an indicator, in that patients with predicted poor prognosis had significantly higher levels of 5-LOXAP than patients with good prognosis (P = 0.0407). Furthermore, patients who died of breast cancer-related causes had significant higher levels of 5-LOXAP than those patients who remained disease free, following a median 10-year followup. A survival analysis has shown that high levels of 5-LOXAP were significantly correlated with overall survival (mean survival 109.6 month vs. 139.4 months, in tumour from patients with high and low levels of 5-LOXAP, P = 0.05). The same disadvantage of high levels of 5-LOXAP was also seen with disease-free survival (105.2 months vs. 135.6 months, P = 0.017). Analysis of 5-LOXAP together with 5-LOX transcript did not enhance the significance of the survival. However, when 5-LOXAP was considered together with 12-LOX, it improved the predictive power for both overall and disease-free survival (109.0 month vs. 143.1 months, P = 0.0156 for overall survival and 98.3 months vs. 141.3 months for disease-free survival, P = 0.0022). In conclusion, 5-LOXAP expression was aberrant in human breast cancer, particularly in aggressive tumours. Furthermore, 5-LOXAP had a significant prognostic value in patients with breast cancer. This identifies 5-LOXAP as a potential therapeutic target in breast cancer.

5-Lipoxygenase-Activating Proteins↗
PubMed2005

[Expression of placental growth factor and pigment epithelium-derived factor in non-small cell lung cancer and the prognostic significance thereof].

OBJECTIVE: To study the expression of placental growth factor (PlGF) and pigment epithelium-derived factor (PEDF) in non-small cell lung cancer, explore the possible role of these factors in the process of neovascular forming, and understand the predict function of these factors to verdict non-small cell lung cancer patients' prognosis. METHODS: Immunohistochemistry was used to detect the expression of PlGF and PEDF in 81 surgical specimens of non-small cell lung cancer from patients. CD31 immunohistochemical staining was used to measure the microvessel density (MVD) so as to investigate the microvessel forming status. The association of these two factors with MVD and their predictive function for the prognosis of non-small cell lung cancer were analyzed. RESULTS: The positive rates of PlGF and PEDF in the non-small cell lung cancer specimens were 43.2% (35/81) and 53.1% (43/81) respectively. There was a positive relationship between PlGF positive expression and MVD, and a negative relationship between PEDF positive expression and MVD. Furthermore, there was a negative correlation between PlGF and PEDF expression. PlGF was an independent prognostic factor in both univariate and multivariate analysis. CONCLUSION: PlGF and PEDF are expressed in non-small cell lung cancer. They are antagonistic to each other in the process of neovessels forming. PlGF plays a more important role in the progression of non-small cell lung cancer and prediction of its prognosis compared with PEDF.

Adult↗
PubMed2005

Expression of Com-1/P8 in human breast cancer and its relevance to clinical outcome and ER status.

Com-1 is a recently discovered molecule that has putative action on the metastatic nature of cancer cells. The molecular action and clinical implication in cancer and prognosis are yet to be established. The current study examined the role of Com-1 in a cohort of patients with breast cancer, with particular emphasis on its relationship with clinical outcomes and ER status. A panel of human breast cancer cell lines were tested. A cohort of breast cancer tumours (n-120) with matched normal non-neoplastic mammary tissues (n = 32) were used. Expression of Com-1 in cancer cells and mammary tissues were studied using conventional and real-time quantitative PCR. Expression profile was analysed against clinical information including tumour grade, staging, nodal status, ER status and survival of the patients. Statistical analysis was Mann-Whitney U-test and Cox Proportion analysis. Com-1 was expressed in breast cancer cell lines. Com-1 protein staining was primarily found in nucleus of epithelial cells of mammary tissues. Tumour cells in breast tissues exhibited a significant reduction in nuclear staining of Com-1, compared to normal epithelial cells (p = 0.0061). Breast tumour tissues expressed similar levels of Com-1, compared to normal non-neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in tumours from patients with predicted good, moderate, to poor prognosis (using Nottingham Prognostic Index) (166 +/- 135 copies of Com1 transcript, 44.3 +/- 36 and 0.64 +/- 0.24, respectively, p = 0.06 by Kruskal-Wallis test). Likewise, node positive tumours had low levels of Com-1, compared to node negative tumours. Tumours from patients who developed metastasis (11.4 +/- 7 copies of Com1 transcript), had local recurrence (41.5 +/- 3.7 copies of Com1 transcript), or who died of breast cancer (0.058 +/- 0.03 copies of Com1 transcript) had lower levels of Com-1, when compared to tumours from patients who remained disease free (156 +/- 129 copies of Com1 transcript). There was no significant correlation between Com-1 and overall survival or disease free survival. When ER status were taken into consideration, it was demonstrated that low levels of Com-1 in ER-beta positive tumours were highly correlated with shorter overall survival of the patients (p = 0.018) (median follow-up 120 months). Com-1 is a nuclear protein, whose expression is reduced in human breast cancer tissues and cancer cell lines. The loss of Com-1 protein is primarily from the nuclear compartment in cancer cells. The expression levels of Com-1 in breast tumours are correlated with the prognosis of the patients and with the long term overall survival in association with ER status.

Base Sequence↗
PubMed2005

Expression of thromboxane synthase, TBXAS1 and the thromboxane A2 receptor, TBXA2R, in human breast cancer.

BACKGROUND: Thromboxane synthase (TxS) metabolizes the cyclooxygenase product, prostaglandin H(2), into thromboxanes. Some of the thromboxanes are known to be biologically active on cancer cells. The aim of the study was to investigate the expression of thromboxane synthases, TBXAS1 and the thromboxane A2 receptor, TBXA2R in a cohort of human breast cancer patients and also to assess their potential clinical relevance. METHODS: Human breast tumour tissues (n = 120) and non-neoplastic mammary tissues (n = 32) were studied. Levels of TBXA2R and TBXAS1 transcripts were quantified using quantitative real-time RT-PCR analysis and correlated with clinical/pathological information including nodal status, grade, prognosis and long term survival (median follow-up period 120 months). RESULTS: Breast tumour tissue expressed higher levels of TBXA2R compared with normal mammary tissues, although the difference was not statistically significant (p = 0.09). There was no difference between tumour and normal tissues for TBXAS1. However, TBXA2R expression was significantly increased in grade 3 tumours(p = 0.006 vs grade 1), while TBXAS1 was significantly reduced in grade 3 tumours (p = 0.026 vs grade 1 tumours). A similar differential expression pattern was seen in tumours from patients with different prognosis, in that patients with predicted poor prognosis had higher, but not statistically different, levels of TBXA2R, and significantly lower levels of TBXAS1 (p = 0.008). Finally, Kaplan-Meier survival analysis has shown that patients with high levels of TBXA2R had significantly shorter disease free survival (103.8 (79.1-128.5) months) compared with those with low levels (123.7 (112.0-135.3)) months, p = 0.043. CONCLUSION: Thromboxane synthases are differentially expressed in human breast cancer. While TBXA2R is highly expressed in aggressive tumours and linked with poor prognosis, TBXAS1 is expressed at significantly low levels in high grade tumours and tumour patients with poor prognosis. TBXA2R thus has a significant prognostic value in clinical breast cancer.

Journal Article↗