High number of tumour-infiltrating lymphocytes is associated with apoptosis in non-small cell lung carcinoma.

Aim: To test whether the number of tumour-infiltrating mononuclear cells (MNC), namely T-lymphocytes (TIL) and, to a lesser degree, B-lymphocytes and macrophages, is associated with tumour cell apoptosis in non-small cell lung carcinoma (NSCLC).

Methods And Results: Eighty-four non-small cell lung tumours were analysed with specific antibodies and the extent of apoptosis was determined using 3'-end labelling of fragmented DNA (TUNEL). All parameters were determined from the same tumour areas.

Regulation of the acute myeloid leukemia cell line OCI/AML-2 by endothelial nitric oxide synthase under the control of a vascular endothelial growth factor signaling system.

It is generally accepted that the vascular endothelial growth factor (VEGF) signal system has no role in the maintenance of normal blood cell formation, although it obviously regulates the development of primitive hematopoiesis during an early stage of embryogenesis. The VEGF signaling pathway, however, might have some role in malignant hematopoiesis, since malignant hematopoietic cells, including acute myeloid leukemia (AML) cells, have been shown to express VEGF and its receptors. In endothelial cells, the VEGF/Flk-1/KDR signal system is a very important generator of nitric oxide (NO) through the activation of its downstream effectors phosphatidylinositol-3-OH-kinase (PI3-K), Akt kinase and endothelial NO synthase (eNOS).

Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1.

Aims: To investigate endothelial nitric oxide synthase (eNOS) expression in malignant mesothelioma and its association with expression of vascular endothelial growth factor (VEGF), its receptors FLK1 and FLT1, and vascular density.

Methods And Results: eNOS, VEGF, FLK1 and FLT1 were studied in 36 histological mesothelioma samples by immunohistochemistry. Two mesothelioma (M14K, M38K) and one non-neoplastic mesothelial cell line (MET-5A) were studied for eNOS mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR).

Expression of caspases-3, -6 and -8 and their relation to apoptosis in non-small cell lung carcinoma.

We analyzed a set of 103 non-small cell lung carcinomas (NSCLCs) for caspase-3, -6 and -8 expression and apoptosis. Additionally, the expression of bcl-2, bax and p53 were studied. Caspase-3 positivity appeared as diffuse, cytoplasmic staining and was restricted to the tumor area.

Widespread expression of thioredoxin and thioredoxin reductase in non-small cell lung carcinoma.

We investigated the expression of thioredoxin (Trx) and thioredoxin reductase (TrxR) in 89 non-small cell lung carcinomas. Additionally, immortalized human bronchial epithelial cells (BEAS 2B) and four human lung carcinoma cells lines (A549, SK-MES-1, CALU-6, and A427) were studied by Western blot and reverse transcription-PCR for the synthesis of Trx and TrxR protein and mRNA expression in vitro. The histological samples were also studied for immunohistochemical p53 and proliferating cell nuclear antigen expression and apoptosis.

Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in several diseases. This study was undertaken to investigate the mRNA synthesis of MMP2, MMP9, membrane-type 1 (MT1)-MMP, and matrix metalloproteinase inhibitors TIMP1 and TIMP2 by in situ hybridization in a set of heart mitral and aortic valves operatively removed due to degenerative or inflammatory valvular diseases. The material consisted of 21 valves, eight with endocarditis and 13 with a degenerative valvular disease.

Up-regulation of thioredoxin and thioredoxin reductase in human malignant pleural mesothelioma.

Thioredoxin (Trx) with a redoxactive dithiol together with NADPH and thioredoxin reductase (TrxR) is a major disulfide reductase regulating cellular redox state and cell proliferation and possibly contributing to the drug resistance of malignant cells. We assessed the Trx system in malignant pleural mesothelioma cell lines, in nonmalignant pleural mesothelium and in biopsies of malignant pleural mesothelioma. The mRNA and immunoreactive proteins of Trx and cytosolic and mitochondrial TrxR were positive in all four human mesothelioma cell lines investigated.

Expression and prognostic significance of catalase in malignant mesothelioma.

Background: Free radicals and antioxidant enzymes (AOEs) may play a critical role in cell proliferation and in the resistance of malignant cells against cytotoxic drugs and radiation. Malignant mesothelioma is a resistant tumor with high levels of manganese superoxide dismutase, a central superoxide scavenging AOE. In the current study, the authors assessed the expression and prognostic role of catalase, an important hydrogen peroxide scavenging AOE, in malignant pleural mesothelioma.

c-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease.

The aim of this work was to evaluate the prognostic and predictive values of c-erbB-2 in breast cancer. 650 patients were enrolled. The amplification/overexpression of c-erbB-2 from fresh frozen or paraffin-embedded breast tumour tissue samples was analysed by polymerase chain reaction (PCR) technique (75%), immunohistochemically (17%) or by Southern blot analysis (8%).

Increased amount of type III pN-collagen in human abdominal aortic aneurysms: evidence for impaired type III collagen fibrillogenesis.

Purpose: This study aimed to characterize the distribution of structural domains of type I and III collagens in the wall of abdominal aortic aneurysms (AAAs), by the use of undilated atherosclerotic aortas (aortoiliac occlusive disease [AOD]) and healthy abdominal aortas as controls.

Methods: Immunohistochemical staining was applied with antibodies for the aminoterminal propeptides of type I (PINP) and type III (PIIINP) procollagens, which represent newly synthesized type I and III pN-collagens. In addition, an antibody against the aminoterminal telopeptide of type III collagen (IIINTP) was used as a means of detecting maturely cross-linked type III collagen fibrils.

eNOS expression is associated with the estrogen and progesterone receptor status in invasive breast carcinoma.

In this study we investigated the immunohistochemical expression of eNOS and nNOS in 80 invasive breast carcinomas. Since NO is known to influence apoptosis and angiogenesis we also determined the apoptotic index of the tumor cells by the TUNEL method and tumor angiogenesis by immunostaining the sections with FVIII-related antigen and assessing the number of positively stained vessels. Respectively, 65% and 11% of the cases expressed cytoplasmic positivity for eNOS and nNOS.

Localization of MT1-MMP, TIMP-1, TIMP-2, and TIMP-3 messenger RNA in normal, hyperplastic, and neoplastic endometrium. Enhanced expression by endometrial adenocarcinomas is associated with low differentiation.

We studied membrane-type matrix metalloproteinase-1 (MT1-MMP), tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, and TIMP-3 messenger RNA (mRNA) using in situ hybridization to elucidate their temporal and spatial expression patterns in normal, hyperplastic, and neoplastic endometrium. All mRNAs studied were expressed weakly in proliferating endometrium but were induced strongly in late secretory endometrium except MT1-MMP. Endometrial hyperplasia samples did not show increased MT1-MMP or TIMP mRNA expression, indicating that the overall expression patterns in hyperplasia are comparable to those in proliferating endometrium under estrogen effect and that synthesis of extracellular matrix proteins, rather than degradation, predominates in this condition.

Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma.

In this study we investigated the immunohistochemical expression of inducible nitric oxide synthase (iNOS) in a set of normal pleural mesothelial tissues, malignant mesotheliomas, mesothelioma cell lines and metastatic pleural adenocarcinomas. Furthermore, the expression of mRNA was assessed in four malignant mesothelioma cell lines in culture. Apoptosis and vascular density in malignant mesotheliomas was assessed by the TUNEL method and by immunohistochemistry with an antibody against FVIII-related antigen.

Proliferation, apoptosis, and manganese superoxide dismutase in malignant mesothelioma.

Proliferation and apoptotic indices of tumour cells may have important prognostic significance. Manganese superoxide dismutase (MnSOD), an important anti-oxidant enzyme, has been shown to decrease proliferation of malignant cells transfected with the MnSOD gene. The aim of the present study was to investigate the indices of cell proliferation and apoptosis and their prognostic significance in human mesothelioma and to assess the effect of MnSOD on the proliferation and apoptosis of the mesothelioma cells expressing high constitutive MnSOD activity.

Tenascin expression and distribution in pleural inflammatory and fibrotic diseases.

We hypothesized that tenascin expression is increased in pleural inflammatory and fibrotic diseases and that its expression can be used as a marker of active pleural involvement. For this purpose we analyzed 71 histological samples of inflammatory and fibrotic pleura from patients with asbestos-induced pleural reaction (n = 6), postcardiac injury syndrome (n = 6), parapneumonic infection and/or empyema (n = 23), tuberculosis (n = 5, rheumatoid disease (n = 1), and fibrosis with inflammation of unknown etiology (n = 30). All 71 cases were studied by immunohistochemistry for tenascin.

Prognostic factors in tongue cancer - relative importance of demographic, clinical and histopathological factors.

The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue have increased during the recent decades in the Western world. Much effort has been made to predict tumour behaviour, but we still lack specific prognostic indicators. The aim of our study was to evaluate the relative importance of the known demographic, clinical and histological factors in a homogeneous population-based group of patients with SCC of the mobile tongue.

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP in hepatocellular and pancreatic adenocarcinoma: implications for tumor progression and clinical prognosis.

In the present study, we used in situ hybridization to study 36 primary hepatocellular carcinomas (HCCs) and 35 pancreatic adenocarcinomas to analyze the expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 mRNAs. In HCCs, MT1-MMP mRNA was mainly expressed by cancer cells and to a lesser extent by stromal cells. MMP-2 mRNA was expressed predominantly by cells of tumor stroma, whereas MMP-9 mRNA was seen mainly in neoplastic epithelial cells.

Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas.

In this investigation, we studied the expression of inducible nitric oxide synthase (iNOS) and its association to apoptosis and angiogenesis in 43 in situ and 68 invasive breast carcinomas. Its expression was studied immunohistochemically using a polyclonal iNOS antibody, and the staining was evaluated both in tumor and stromal cells. Apoptosis was detected by 3' end labeling of fragmented DNA (terminal deoxynucleotidyl transferase-mediated nick end labeling method).

A high number of tumor-infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma.

Tumor-infiltrating lymphocytes, apoptosis, and angiogenesis have a pivotal role in tumor growth control. This study was undertaken to analyze the associations of these factors and their role in the prognosis, defined as survival time, of 56 patients operated on for small cell lung carcinoma (SCLC). Immunohistochemically detected T cells and macrophages were the most abundant tumor-infiltrating lymphocytes in SCLC, whereas the number of B cells was small.

Atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity.

Background: Bronchopulmonary carcinoid tumors can be divided into typical and atypical carcinoids according to their histologic and clinical features. Atypical carcinoids tend to have less predictable biologic behavior and are associated with a worse prognosis than typical carcinoids. The authors examined apoptosis and the expression of apoptosis regulating proteins Bcl-2, Bax, Bak, and Mcl-1 in 21 typical and 10 atypical bronchopulmonary carcinoid tumors.

Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma.

Although several immunohistochemical markers are available, differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura is difficult. We have found that the immunoreactivity of manganese superoxide dismutase (MnSOD), an important antioxidant enzyme, is high in mesothelioma compared to healthy pleural mesothelium. The aim of the present study was to investigate whether MnSOD can be used in the differential diagnosis of malignant mesothelioma and metastatic adenocarcinoma of the pleura.

Tenascin mRNA expression at the foci of recent injury in usual interstitial pneumonia.

To elucidate which cells are synthesizing tenascin in usual interstitial pneumonia (UIP) we have analyzed thoracoscopic or open lung biopsies from 30 patients with UIP by mRNA in situ hybridization, using (35)S-labeled tenascin RNA probes. The phenotype of the cells expressing tenascin mRNA was confirmed by immunohistochemical stainings of serial sections with antibodies against alpha-smooth muscle actin and human cytokeratin. The results demonstrate that tenascin is expressed at the foci of recent lesions consisting of intralumenal or incorporating loose fibrotic buds.

Apoptosis in gallbladder carcinomas and dysplasias, its relation to the expression of caspases 3, 6 and 8 and apoptosis regulating proteins bcl-2, mcl-1 and bax.

In this study we investigated apoptosis and the expression of caspases 3, 6 and 8 and bcl-2, mcl-1 and bax in 39 gallbladder carcinomas and 7 epithelial dysplasias. The average apoptotic index was 0.68 +/- 0.

Apoptosis and expression of caspases 3, 6 and 8 in malignant non-Hodgkin's lymphomas.

In this study we investigated the immunohistochemical expression of caspases 3, 6 and 8 in 85 malignant non-Hodgkin's lymphomas and in 4 hyperplastic lymph nodes. The extent of apoptosis and the immunohistochemical expression of bcl-2 and bax was also studied. Caspase 3 immunoreactivity was seen in 84/85 (99%), caspase 6 in 46/85 (54%), and caspase 8 in 66/85 (78%) lymphomas.

Apoptosis and expression of apoptosis regulating proteins bcl-2, mcl-1, bcl-X, and bax in malignant mesothelioma.

We investigated apoptosis and the expression of bcl-2, mcl-1, bcl-X, and bax in histological sections from 35 malignant mesotheliomas and 21 metastatic adenocarcinomas. Moreover, the expression of bcl-2, mcl-1, bcl-X, and bax were assessed by Western blotting in nonmalignant human mesothelial cells (Met5A) and seven malignant cell lines. The apoptotic index in mesotheliomas was 1.