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Biomedical subjects

A M Groeger

Publications and source records attributed to A M Groeger.

At least 19 recordsLinked to original sources
PubMed2005

Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer.

BACKGROUND: Experimental evidence suggests that lung cancer development and progression can be linked to an increased proliferation rate. AIMS/METHODS: To evaluate the immunohistochemical expression of seven components of the cell cycle machinery in a series of well characterised non-small cell lung cancer (NSCLC) specimens (n = 105). RESULTS: Multivariate analysis revealed that simultaneous loss of expression of three of these factors--cyclin D1, the cyclin dependent kinase inhibitor p16, and the tumour suppressor retinoblastoma protein Rb2/p130--correlated with survival, confirming the hypothesis that the cyclin D1-p16-retinoblastoma tumour suppressor pathway is inactivated in most lung cancer samples. CONCLUSIONS: These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancer and support the idea that functional cooperation between different cell cycle regulatory proteins constitutes another level of regulation in cell growth control and tumour suppression.

Aged↗
PubMed2004

Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers.

AIMS: Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. In this study we evaluated the possible role of p53 and Bcl-2 gene family members as prognostic factors for non-small-cell lung cancer. METHODS AND RESULTS: We investigated the immunohistochemical expression of p53 and Bcl-2 gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl-2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over-expression of bax and Bcl-xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with patient survival time. CONCLUSIONS: This study confirms a relevant role for apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl-2 as a prognostic factor for this tumour.

Apoptosis↗
PubMed2004

Mediastinal hibernoma: a case report.

Hibernomas are rare benign tumours that arise most often in adults from the remnants of fetal brown adipose tissue. They usually affect muscle and subcutaneous tissue and are asymptomatic and slow growing. The distribution of this tumour follows the sites of persistence of brown fat. Out of more then 100 cases described in the word literature only three hybernomas were mediastinal. A recent clinicopathological study of 170 cases from the Armed Forces Institute of Pathology confirmed the exceptionality of the intrathoracic location. This report describes a very rare case of mediastinal hibernoma in a young man.

Adult↗
PubMed2004

Analysis of cell cycle regulator proteins in non-small cell lung cancer.

BACKGROUND/AIMS: Abnormalities of the proteins involved in cell cycle checkpoints are extremely common among almost all neoplasms. This study aimed to investigate the expression of four components of the cell cycle machinery-p21, p16, p53, and proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC). METHODS: The expression of p21, p16, p53, and PCNA was examined in 68 well characterised NSCLC specimens using immunohistochemistry. The coregulation of these proteins and their influence on survival were analysed using both univariate and multivariate analyses. RESULTS: By univariate analysis, the expression of all the proteins examined, except for PCNA, was significantly correlated with survival. In multivariate analysis, the only immunohistochemical parameter able to influence overall survival was p16, confirming the hypothesis that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer samples. Finally, the group of patients with NSCLC who were negative for both p21 and p16 had a significantly shorter overall survival. CONCLUSIONS: These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancers, and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumour suppression.

Adult↗
PubMed2004

Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma.

BACKGROUND: A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53. METHODS: Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses. RESULTS: A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2. CONCLUSIONS: These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.

Cell Cycle Proteins↗
PubMed2002

Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival.

BACKGROUND: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma. METHODS: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences. RESULTS: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001). CONCLUSIONS: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.

Antigens, Viral↗
PubMed1999

Independent prognostic role of p16 expression in lung cancer.

OBJECTIVES: The cyclin-dependent kinase p16 (also known as Ink4A, Mts1, Cdkn2, and Cdkn4i) has been proposed as a tumor suppressor gene mapped on chromosome segment 9p21. This study evaluated p16 protein expression in 135 lung cancer specimens and investigated potential genetic alterations occurring in this gene. RESULTS: We found altered p16 immunohistochemical expression to be a frequent event in lung cancer and to be independent of either the histologic type or any other clinical-pathologic feature. Western blot analyses performed on about one third of the specimens correlated highly with these results. In addition, we found p16 immunohistochemical expression to be a favorable prognostic factor in lung cancer in that its reduction or loss correlated with a worse outcome for the patients. Polymerase chain reaction amplification and direct sequencing of p16 exons 1 and 2 revealed no mutations, indicating that p16-altered expression in lung cancer is not necessarily linked to mutational events of these genes. CONCLUSIONS: We conclude that p16-altered expression is both an independent and frequent event in lung cancer and may have an important role in tumorigenesis and in malignant progression of a significant proportion of these cancers. However, the actual incidence and relevance of p16 mutations in this neoplasm continues to be debated, and its analysis seems inconclusive. Our results suggest a prognostic role for the immunodetection of this protein on formalin-fixed and paraffin-embedded specimens. They further suggest its routine use in the evaluation of the frequently unpredictable behavior of lung cancer.

Adenocarcinoma↗
PubMed1999

Prognostic role of cyclin D1 in lung cancer. Relationship to proliferating cell nuclear antigen.

We developed an immunohistochemical assay specific for cyclin D1 and suitable for formalin-fixed and paraffin-embedded sections, to evaluate cyclin D1 expression in a group of 135 surgically resected lung-cancer patients for the purpose of investigating the prognostic role of this protein in lung cancer. In addition, we compared cyclin D1 expression with the expression of proliferating cell nuclear antigen (PCNA), considered to be a reliable index of the proliferation rate. We found cyclin D1 expressed in more than 60% of the neoplastic cells in 26.5% of our specimens. A total of 24.5% of the specimens showed cyclin D1 expression in a percentage of cells ranging from 30 to 60%; 36.7% of the specimens expressed cyclin D1 in less than 30% of the cells; and 12.2% of the specimens expressed cyclin D1 in less than 1% of the evaluated cells. Western blot analyses confirmed the specificity of this assay by correlating statistically in a highly significant fashion with the immunohistochemical results (P = 0.0003). Furthermore, we found a direct relationship between cyclin D1 and PCNA immunodetection (P = 0.0004), which correlated cyclin D1 overexpression with a higher tumor proliferation rate. When we analyzed our data statistically, cyclin D1 expression was found to be a negative prognostic marker (P < 0.00005) whose expression correlates with a shorter patient survival time.

Adenocarcinoma↗
PubMed1997

Survival after surgical treatment of recurrent pulmonary metastases.

OBJECTIVE: Resection of lung metastases is a generally accepted therapeutic strategy today. This retrospective study was performed in order to estimate the value of an aggressive surgical approach in recurrent metastatic disease of the lung. METHODS: The survival rates of 42 patients undergoing repeated resectional treatment for recurrent lung metastases (group A) were compared to the outcome of a total of 288 patients after a single surgical intervention for lung metastases (group B). Survival rates and the relative effects of the various prognostic factors were calculated according to Kaplan-Maier and Mantel Cox or Wilcoxon test. Histology of the primary tumors in group A consisted of 18 carcinomas, 22 sarcomas and two melanomas, in group B the distribution was 64% carcinoma, 27% sarcoma and 9% melanoma. The mean follow-up period was 88.5 months for group A and 27 months for group B. RESULTS: The overall survival rate for group A was 48% at 5 years and 30% at 10 years, the survival rate for group B was 34% at 5 years. CONCLUSION: Long-term survival rates superior to those after single resectional treatment for lung metastases encourage an aggressive surgical approach for this disease.

Adolescent↗
PubMedDate not supplied

Expression of AP-2 transcription factor and of its downstream target genes c-kit, E-cadherin and p21 in human cutaneous melanoma.

The AP-2 transcription factor plays a pivotal role in regulating the expression of several genes involved in tumor growth and progression of melanoma. We determined, by Western blot, variation in the level of expression of AP-2 and three of its downstream targets, c-kit, E-cadherin, and p21 in several human melanoma cell lines and, by immunohistochemistry, in a group of 99 histological samples including benign and malignant melanocytic lesions. A significant negative correlation between AP-2 expression level and tumor thickness was found. Moreover, AP-2 expression was positively associated with E-cadherin and c-kit expression. In contrast, there was a significant negative association between AP-2 and p21 expression levels. These findings suggest that p21 is independent of AP-2 transactivator function during the latest phases of melanoma progression. Finally, AP-2, c-kit, E-cadherin, and p21 expression levels did not show to be able to distinguish between dysplastic nevi and nevi without dysplasia. We conclude that changes in the expression of these proteins are involved in the later phases of melanoma progression, and may be responsible for the transition from local invasive melanoma to metastasis.

Blotting, Western↗
PubMedDate not supplied

Bcl-2 protein expression correlates with nodal status in non small cell lung cancer.

We investigated the immunohistochemical expression of bcl-2 in 55 non small cell lung cancer patients in order to understand if the altered expression of this gene is involved in the development of this kind of neoplasm. Our results showed bcl-2 immunopositivity to be a frequent event in non small cell lung cancer (54.5%) with a higher expression in squamous carcinomas compared to adenocarcinomas (p = .04). In addition, we found a positive correlation between bcl-2 expression levels and nodal status (p < .003). We suggest that bcl-2 immunostaining could be considered as marker of loco-regional invasivity.

Adenocarcinoma↗
PubMedDate not supplied

Frequent high expression of bax pro-apoptotic protein in non-small cell lung cancer.

Bax, bcl-2 and their homologues regulate a distal step in an evolutionary very well conserved pathway of apoptotic cell death. It plays a crucial role in the balance between proliferation rate and cell viability. Thus in the last years the attention of the scientific community towards these proteins has remarkably increased, in particular in the oncologic field. We developed an immunohistochemical assay allowing us to evaluate the bax expression in formalin fixed and paraffin embedded lung cancer tissues to investigate bax expression in a cohort of 55 patients affected by non-small cell lung cancer. We detected high expression of bax in 72.7% of our patients. When we statistically analyzed our data we did not find any correlation between bax expression and any clinicopathologic parameters (sex, age, TNM status, tumor grade, histological type). In conclusion, our study shows the frequent overexpression of bax, and this highlights the "apoptotic tendency" of cells during the neoplastic proliferation. But, the role of bax in non-small cell lung cancer pathogenesis still remains unclear and further studies of large numbers of patients, including different stage groups, are needed to better define the involvement of this protein in the complex mechanism of lung carcinogenesis.

Adenocarcinoma↗
PubMedDate not supplied

The effects of volatile anesthetic agents on pulmonary surfactant function.

The purpose of this article is to review the findings from research directed at understanding the effects of volatile anesthetics on the respiratory surface known as pulmonary surfactant. Anesthetics have long been known to have a disruptive effect on biological membranes. This review will highlight the interactions of volatile anesthetics with pulmonary surfactant. This paper has emphasized the interaction of volatile anesthetics with the pulmonary surfactant monolayer versus the lipid bilayer. The goal of this review is to uncover to what extent this understanding has progressed in forty years. Although the goal is quite broad, the information gathered and the advice given is specific. Theories of anesthesia and surfactant structure and function are summarized and discussed in light of early physico-chemical approaches and extend to an era where powerful new three-dimensional structural techniques can be used to answer this question.

Anesthetics, Inhalation↗
PubMedDate not supplied

Colonic type adenocarcinoma of male urethra.

A case of rare primary adenocarcinoma of the bulbomembranous portion of the male urethra is presented. The histological and immunohistochemical characteristics of this tumor are identical to those of colon adenocarcinomas. The pathogenesis can be explained either by neoplastic degeneration of globet cells found in the urethral epithelium or by malignant degeneration of persistent glandular elements that are embryonal residues. The patient was successfully treated with transurethral prostatectomy and with a high dose of radiation therapy.

Adenocarcinoma↗
PubMedDate not supplied

Expression of p21 in non small cell lung cancer relationship with PCNA.

The first cyclin dependent kinase inhibitor to be discovered was the p21 cdk interacting protein (a.k.a., WAF1, Cip1, CAP20, Sdi1, mda6). p21 expression may or may not be dependent on p53. This pathway also inhibits DNA replication by merit of p21's interaction with PCNA, but it has also been shown that this same inhibitory interaction with p21 does not affect PCNA DNA repair abilities. We assessed the immunohistochemical expression of p21 protein in 60 curative surgical resected non small cell lung cancers relating it to the expression of PCNA to clarify the contribution of the p21/PCNA pathway to the development of NSCLC. We did not find any relationship between PCNA and p21 expression. This last result may indicate that the mechanism by which PCNA controls the DNA repair is the most important activity of this protein during lung cancer progression and development, compared to its contribution to cell proliferation. In fact, this last event is strongly counteracted by p21 expression, which in this last case works as an inhibitor of PCNA expression. In conclusion this study highlighted the important role of the p21/PCNA pathway in lung carcinogenesis, pointing out the contribution of PCNA to the response to lung aggression and not only it's role as a proliferation index. Therefore, these results offer a background to further study to evaluate potential novel therapeutic approaches to lung cancer treatment.

Adenocarcinoma↗
PubMedDate not supplied

Intrapulmonary teratoma associated with thymic tissue.

A case of benign, cystic intrapulmonary teratoma occurring in the right lobe of a 22-year old female is described with grossly and microscopically findings. The connection between the tumor and the segmental bronchus, together with the absence of germ cell neoplasms in other locations, clearly established the true intrapulmonary nature of the lesion. The unusual finding of thymic tissue within the wall supports the possible origin from the third pharyngeal pouch.

Actins↗
PubMedDate not supplied

Detection of circulating malignant cells by RT-PCR in long-term clinically disease-free I stage melanoma patients.

Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging cancer. In this report, 43 melanoma patients (including 4 in situ melanoma patients) were tested for tyrosinase mRNA in blood by RT-PCR. All patients had melanoma thinner than 1.5 mm (stage I). Circulating melanoma cells were detected in 8 (18.6%) out of 43 MM patients tested: 5 (16.1%) of 31 patients with melanoma thinner than 0.76 mm and 3 (42.8%) out of 7 patients with melanoma thicker than 0.76 mm. Moreover, in the tyrosinase-negative group we found only 4/31 patients (13%) with histologic signs of regression, but in the tyrosinase-positive group, 3 out of 8 patients (37.5%) showed, at histologic examination, signs of regression. At the time of this analysis all the patients enrolled (tyrosinase-negative and tyrosinase-positive ones) were free of disease, probably due to the short median time of follow-up after the inclusion in the study. The presence of regression is an important cause of melanoma understaging and the tyrosinase test could represent an effective tool in order to achieve a realistic staging in this subgroup of melanoma patients. Probably, maximum sensitivity of the diagnostic RT-PCR approach to monitor MM patients with either localized or advanced disease could be achieved by using additional markers expressed with high frequencies in melanoma. We propose that one such marker could be the sign of regression.

Adolescent↗