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PubMed2006

[Expression of Smac in Stage I-II non-small cell lung cancer and its clinical significance].

BACKGROUND & OBJECTIVE: Second mitochondrial activator of caspase (Smac) was recently identified as a new apoptogenic factor that is released from mitochondria. It promotes apoptosis by antagonizing inhibitor of apoptosis proteins, and shows in vitro antitumor effect. However, little is known about its role in non-small cell lung cancer (NSCLC). This study was to investigate the expression of Smac in stage I-II NSCLC, and explore its correlations to clinicopathologic features and prognosis. METHODS: Immunohistochemistry and tissue microarray were used to detect the expression of Smac in 213 specimens of stage I-II NSCLC. Its correlations to clinicopathologic features and prognosis of NSCLC were analyzed. RESULTS: The 5-year survival rate of the patients with stage I NSCLC was 61.9%, and that of the patients with stage II NSCLC was 30.0%. Smac protein was mainly localized in cytoplasm. When the positive cells percentage of 75% was used as a cutoff point, 129 (39.4%) samples showed high Smac expression, and 84 (60.6%) showed low Smac expression. Smac expression was not correlated to sex, age, histological type, blood type and prognosis of the patients, whereas the positive rate of Smac was significantly higher in the patients with lymph node metastasis than in the patients without lymph node metastasis (58.3% vs. 37.0%, P<0.05). CONCLUSION: Smac protein might be correlated to lymph node metastasis of NSCLC.

Adolescent↗
PubMed2006

Clusterin plays an important role in hepatocellular carcinoma metastasis.

To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, P<0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (P<0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

Adipokines↗
PubMed2006

Galectin-3 expression is associated with tumor progression and pattern of sun exposure in melanoma.

PURPOSE: Most studies accept a multistep pathogenic process in melanoma that may include the phases of benign nevi and dysplastic nevi, melanoma, and metastatic melanoma. Dysregulation of cellular proliferation and apoptosis is probably involved in melanoma progression and response to therapy. We have studied the expression of galectin-3, a beta-galactoside-binding protein involved in apoptosis, angiogenesis, and cell proliferation, in a large series of melanocytic lesions, and correlated the expression with clinical and histologic features. EXPERIMENTAL DESIGN: Tissue microarray blocks of 94 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic or nuclear expression of galectin-3. RESULTS: Primary and metastatic melanomas expressed galectin-3 at a significantly higher level than nevi in both cytoplasm and nuclei (P<0.0073). There was a significant association between anatomic source (as indirect indication of level of sun-exposure) and cytoplasmic and nuclear expression. Lymph node and visceral metastases had a higher level of expression than s.c. lesions (P<0.004). Interestingly, there was an almost significant finding of worse survival in those patients with lesions showing higher levels of cytoplasmic than nuclear galectin-3 expression (log-rank test, P=0.06). CONCLUSIONS: Melanocytes accumulate galectin-3 with tumor progression, particularly in the nucleus. The strong association of cytoplasmic and nuclear expression in lesions of sun-exposed areas suggests an involvement of UV light in activation of galectin-3.

Biomarkers, Tumor↗
PubMed1998

Reduced expression of tissue inhibitor of metalloproteinase in nodal metastasis of stomach cancer.

The matrix metalloproteinases (MMPs) have been associated with tumor cell invasion and metastasis of human cancers by mediating the degradation of extracellular matrix components. Therefore, these enzymes and their inhibitor (TIMP-2) constitute promising targets in the development of anticancer therapies. In order to investigate the correlation between expressions of TIMP-2, MMPs and clinical outcome, immunohistochemical staining of MMP-2, MMP-9, and TIMP-2 were performed on paraffin-embedded tissue sections of 15 early gastric cancers (EGC) and 15 advanced gastric carcinomas (AGC) without nodal metastasis and 15 AGC with nodal metastasis (AGCn+). MMP-2 and MMP-9 were expressed in neoplastic cell plasma membrane in 83.3% and 88% of cases of AGC, respectively with inter-tumoral variability of staining intensity. MMP-2 and MMP-9 staining were not correlated with presence of nodal metastasis or degree of invasion depth at the time of diagnosis (p>0.05). The immunoreactivity of TIMP-2 was detected in the peri-tumoral stroma. Residual benign stomach tissue showed no or weak immunoreactivity for TIMP-2 staining. Among AGC, neoplasms with diffuse and strong TIMP-2 staining have less frequent metastasis (28.6%) than cases with focal and weak (68.8%) (p<0.05). Early gastric cancer revealed diffuse and strong TIMP-2 expressions. We conclude that clinical outcome such as depth of invasion or metastasis is more closely related to the expression of TIMP-2 than the corresponding MMPs.

Collagenases↗
PubMed2003

The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology.

The aim of this study was to determine the expression of proteinases and inhibitors from the matrix metalloproteinase (MMP) (MMPs 1, 2, 3, 9, tissue inhibitors of metalloproteinases (TIMPs) 1, 2) and plasminogen activator ((PA) urokinase (uPA), tissue type (tPA), uPAR, plasminogen activator inhibitors (PAIs) 1, 2) systems in colorectal cancer pathology by gelatin zymography, enzyme-linked immunosorbent assays (ELISAs) and quenched fluorescent substrate hydrolysis. The levels of all studied MMPs, uPA, uPAR, TIMP-1 and PAIs were significantly greater in tumour tissues than normal tissues. However, tPA and TIMP-2 were greater in normal colon (P<0.05, Mann-Whitney) e.g. PAI-1: tumour, median 14.9 (range 0.2-80.2) ng/mg total protein; normal, 2.1 (0.1-65.0). Tumour levels of several factors, in particular MMP-1 and PAI-1, correlated with pathology, i.e. Dukes' stage, differentiation, lymphatic or vascular invasion and tumour depth. The interactions between proteinase systems in colorectal cancer are complex and the balance between active proteinases and their inhibitors is important for extracellular matrix (ECM) degradation/remodelling at each stage of the metastatic cascade.

Adult↗
PubMed1988

[Stewart-Treves syndrome of the edematous arm following breast cancer operation].

In 1948, Stewart and Treves (158) described a lymphangiosarcoma on the edematous arm for the first time with reference to six cases involving arm edema after breast cancer operation. Since their publication, a further 313 cases have become known. In 1982, with communication of one case we published a statistical compilation comprising of 248 cases (Zeitschrift für Lymphologie VI, 1982, 51-66). A statistical compilation totalling 290 observations is now presented on the basis of further studies of the older literature supplemented by observations of the last six years including two of our own cases. So far, a total of 319 single observations has become known: 21 cases of Yap et al. (182), eight cases of Oshmianskaia et al. (123) and 290 cases in the statistical compilation we have drawn up and which is the basis of this publication. By histological investigation of the tissue material taken from a female patient within six weeks (exploratory excision, radical excision), detailed information could be obtained on the histological development of the Stewart-Treves-Syndrome (STS) from a preneoplasia to a mature lymphangiosarcoma. The second female patient is a relatively rare observation of an STS of fulminant course which remained restricted to the extremity, chest wall and neighboring parts of the back during the entire course.

Aged↗
PubMed1995

Clinical value of pretreatment serum Cyfra 21-1, tissue polypeptide antigen, and squamous cell carcinoma antigen levels in patients with cervical cancer.

BACKGROUND: The clinical value of pretreatment serum concentrations of cytokeratin 19 fragments, measured by Cyfra 21-1, was compared with tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) in 78 patients with squamous cell cervical cancer. METHODS: Serum levels were compared with tumor stage, size, lymph node status, parametrial involvement, and prognostic data. The clinical performance of the different tests was evaluated by their receiver operating characteristic (ROC) curves. RESULTS: Serum levels of all markers were related significantly to tumor stage and size. Elevated serum levels of these markers were not found to be predictive for the presence of lymph node metastases. In contrast, a positive relation was found between quantitative serum Cyfra 21-1, TPA, and SCC-Ag levels and the presence of either lymph node metastases or parametrial involvement (i.e., extracervical disease). An elevated, i.e. positive, serum Cyfra 21-1 level was related significantly to the presence of extracervical disease (P = 0.020). The clinical performance of each serum marker in predicting lymph node metastases or parametrial involvement appeared to be similar as expressed by their ROC curves. In the univariate analysis, Cyfra 21-1, TPA, and SCC-Ag showed prognostic value with respect to disease free interval and survival. Elevated serum levels were associated with a poor prognosis. However, after adjusting for tumor stage and size, none of these markers remained statistically significant. CONCLUSIONS: Cyfra 21-1 may be of additional value in assessing stage of disease, tumor size, and the presence of extracervical disease in patients with cervical cancer. Determining its value during follow-up warrants further study.

Adult↗
PubMed1994

Plasminogen activators and their inhibitors in non-small cell lung cancer. Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination.

BACKGROUND: Evidence suggests that plasminogen activators and their inhibitors play an important role in tumor spread. METHODS: In this study, we measured the antigen levels of urokinase (u-PA), tissue plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and type 2 plasminogen activator inhibitor (PAI-2), and cancer tissue (19 adenocarcinomas and 19 squamous cell carcinomas) and normal lung tissue. RESULTS: u-PA, PAI-1, and PAI-2 antigen levels in cancer tissue were significantly higher than those in normal tissue (P < 0.001 in u-PA and PAI-1; P < 0.005 in PAI-2), whereas t-PA antigen levels in cancer tissue were significantly lower than those in normal tissue (P < 0.005). In case with lymph node involvement (LN+ cases), PAI-2 antigen levels were significantly lower than those in cases without lymph node involvement (LN- cases) (P < 0.02), whereas there was no difference in either u-PA or PAI-1 antigen levels between these two groups. Furthermore, u-PA antigen levels showed a significant positive correlation with PAI-2 antigen levels in LN- cases (r = 0.696; P < 0.005), although there was no correlation between these two parameters in LN+ cases. CONCLUSIONS: The antigen levels of u-PA, PAI-1, and PAI-2 in cancer tissue were significantly higher than those in normal tissue, and lower content of PAI-2 was associated with lymph node metastasis.

Adenocarcinoma↗
PubMed1977

Review of local soft tissue recurrence of breast cancer irradiated with and without actinomycin-D.

Between 1962 and 1973, regionally recurrent breast cancer was treated in 156 patients by irradiation alone or irradiation with concurrent actinomycin-D. Thirty-two patients were entered into a randomized trial, and 124 patients were retrospectively reviewed. Local control with irradiation alone was achieved in 48 of 80 patients (60%) and in 60 of 76 patients (79%) treated with irradiation and actinomycin-D (p less than .05). Results were remarkably similar in the randomized and retrospective series.

Breast Neoplasms↗
PubMed1987

[Surgical treatment of malignant soft tissue tumors].

The ultimate survival of patients with soft tissue sarcoma is determined by a number of factors. Radical removal by adequate surgery is one of the most important factors together with early treatment and chemotherapy. We usually select curative wide resection, amputation, or resection after radiotherapy as forms of radical surgery for soft tissue sarcomas according to each clinical stage. The method of curative wide resection is based on biological barrier effects. In this report we discuss the operative results obtained in 148 cases of soft tissue sarcoma which we have treated over the past ten years, and also discuss the causes of recurrence after radical operation. Among 55 primary NoMo which were treated by the curative wide resection cases, the recurrence rate was 5.5%, the metastatic rate was 21.8%, and 5-year survival was 79.3%. These results were better than those for 30 recurrent and additional NoMo cases. Of cases involving the extremities, 81% were controlled by limb-saving operations.

Adult↗
PubMed1994

Both the cytosols and detergent extracts of breast cancer tissues are suited to evaluate the prognostic impact of the urokinase-type plasminogen activator and its inhibitor, plasminogen activator inhibitor type 1.

The serine protease urokinase-type plasminogen activator (uPA) plays a key role in tumor-associated proteolysis in malignant solid tumors. Proteolytic activity of uPA is controlled by its naturally occurring plasminogen activator inhibitor type 1. As an initial observation, a correlation of enzymatic uPA activity in breast cancer cytosols with prognosis was described in 1988 (Duffy et al., Cancer (Phila.), 62: 531-533, 1988). A pronounced prognostic impact of uPA, independent of classical risk parameters, was then first demonstrated in detergent-extracted (Triton X-100) breast cancer tissues by applying enzyme-linked immunosorbent assay techniques (Jänicke et al., Lancet, 2: 1049, 1989; Fibrinolysis, 4:69-78, 1990; Duffy et al., Cancer Res., 50: 6827-6829, 1990). In addition, not only uPA but also plasminogen activator inhibitor type 1 were shown to be of prognostic value in breast cancer (Jänicke et al., Semin. Thromb. Hemostasis, 17: 303-312, 1991; Breast Cancer Res. Treat., 24: 195-208, 1993). Subsequently, the prognostic value of uPA and plasminogen activator inhibitor type 1 was also confirmed in studies using archived "cytosol fractions" of breast cancer tissues (Foekens et al., Cancer Res., 52: 6101-6105, 1992; Spyratos et al., J. Natl. Cancer Inst., 84: 1266-1272, 1992; Grondahl-Hansen et al., Cancer Res., 53: 2513-2521, 1993; Sumiyoshi et al., Int. J. Cancer, 50: 345-348, 1992). A direct comparison of both methods with regard to prognosis, however, was lacking. We therefore prepared both the detergent-treated tissue extracts and the cytosol fractions from the same breast cancer specimens to allow a direct comparison of both methods. In 247 breast cancer patients investigated, the Triton X-100-extracted tissues revealed about twice as much uPA antigen (uPATx: median, 2.32 ng/mg protein) than the cytosol fractions (uPAcyt: median, 1.07 ng/mg protein). In contrast, the presence of Triton X-100 did not result in an increase of PAI-1 (PAI-1Tx: median, 6.34 ng PAI-1/mg protein) compared to the cytosol fractions (PAI-1cyt: median, 7.15 ng PAI-1/mg protein). Good correlations between uPATx and uPAcyt (R = 0.72) and between PAI-1Tx and PAI-1cyt (R = 0.88) were observed. Furthermore, PAI-1 and uPA are moderately correlated with each other (uPATx versus PAI-1Tx: R = 0.40; uPAcyt versus PAI-1cyt: R = 0.39). The prognostic power of uPA showed its best advantage in Triton X-100-extracted tissues (RR = 3.22), most pronounced in the subgroups of node-negative and premenopausal patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗
PubMed1989

Sonographic detection and fine-needle aspiration biopsy of nonpalpable recurrent or metastatic melanoma in subcutaneous tissues.

Subcutaneous or lymph node metastases from melanoma may not be palpable because of their small size, their distance from the skin surface, or their location in an area of fibrosis due to previous surgery or irradiation. High-resolution sonography has been used to detect clinically occult foci of recurrent or metastatic melanoma, whereas real-time, ultrasound-guided, fine-needle aspiration biopsy provided cytologic confirmation. Following excision of cutaneous melanoma, sonographic follow-up of the areas of the surgical scar and lymphatic drainage is recommended whenever residual disease is suspected or when clinical evaluation is limited by postoperative or postradiation changes. Any nonpalpable hypoechoic mass detected in those areas should have a biopsy under real-time sonographic guidance.

Biopsy, Needle↗
PubMed1989

[Plasma and tissue concentration of tegafur by a new soft capsule type suppository in colorectal carcinoma].

Plasma, tissue, and Lymph-node concentrations of tegafur and 5-FU were examined in 19 patients with colonic and rectal carcinoma after administration of tegafur by a new soft capsule type suppository: Plasma levels of tegafur and 5-FU after administration by soft capsule were much higher than those seen using supp. type suppositories. Tissue levels of 5-FU were high in tumor tissue compared to levels found in adjacent normal tissue. Lymph node levels of 5-FU were higher than plasma levels. Lymph node levels of 5-FU in the first-group lymph nodes were higher than in the second-group. These results suggest the clinical usefulness of administration of tegafur by soft-capsule suppository.

Aged↗
PubMed2001

[The role of diagnostic PET in treatment planning before tumor surgery].

Positron emission tomography (PET) can be used for the noninvasive biochemical analysis of lesions whose benign or malignant nature cannot be assessed by morphological methods alone. This information and the possibility of quantitation are the reasons for the successful application of PET in staging, diagnosis of tumor recurrence and therapy monitoring in different malignant tumors. Since malignant tumors show characteristic biochemical properties with an enhancement of glucose metabolism, 18fluorodeoxyglucose (FDG) has proven useful for oncologic studies. This paper deals with the influence of PET on the surgical and other therapeutic procedures in patients with cancer of the lung, thyroid, intestine, breast and soft tissue. PET is useful for the mediastinal staging of patients with lung cancer and the evaluation of persistent tissue or tumor recurrence after treatment of lung cancer and colorectal cancer. Furthermore, important information is obtained for the staging of colorectal cancer and mammary carcinoma. PET is also indicated in patients with colorectal cancer or mammary carcinoma and a rising tumor marker. An important future application is therapy monitoring. New treatment modalities will raise new problems in terms of functional diagnosis for the different imaging procedures. Therefore, future work has to concentrate on the establishment of diagnostic algorithms for the optimization of therapy.

Breast Neoplasms↗