Pinelopi Korkolopoulou

Hormone receptors in non-malignant meningiomas correlate with apoptosis, cell proliferation and recurrence-free survival

Aims:  A retrospective immunohistochemical and statistical analysis of patients with non‐malignant meningiomas was undertaken to determine the correlation of steroid hormone receptor status with apoptosis, tumour cell proliferation, clinicopathological characteristics and prediction of recurrence.

Prognostic relevance of apoptotic cell death in non‐Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression

Aims: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non‐Hodgkins lymphomas (NHL).

Apoptotic markers for tumor recurrence: a minireview.

The control of apoptotic mechanisms is integral to many aspects of tumor biology and appears to be involved in the process of recurrence. Apoptosis serves as an essential mechanism to prevent the proliferation of cells with a higher mutation rate, thus tempering malignant transformation. Most antineoplastic therapies function by triggering apoptosis in sensitive cells. Resistance to treatment may result from specific inhibition of apoptotic signaling. Chemotherapy or radiation may increase the mutation rate and hasten tumor evolution in cancer cells that are resistant to apoptosis. Summarizing the current evidence regarding the usefulness of various apoptotic markers for predicting tumor recurrence, the most extensively studied appear to be bcl-2 and p53, as well as the apoptotic rate itself, with promising prognostic potential in several neoplasias. Investigative results, however, mostly refer to multiple single-center retrospective studies, awaiting validation by large prospective clinical trials. Despite initial optimism, it becomes apparent that the measurement of one or more gene products is inadequate to directly predict a phenomenon as complex as the clinical outcome. One of the challenges that is only beginning to be addressed is the combined assessment of traditional prognostic parameters and molecular biomarkers by creating models or equations to predict the likelihood of recurrence. Such screening of patients may help define prognostic categories and influence treatment decisions.

Effects of oral administration of (L)-arginine, (L)-NAME and allopurinol on intestinal ischemia/reperfusion injury in rats.

AIMS Intestinal ischemia/reperfusion (I/R) injury is implicated in many clinical conditions, and it performs a fundamental role in their pathophysiologies. Oral administration of antioxidants and nitric oxide (NO) donors ameliorate intestinal injury. Here, the effects of l-arginine, allopurinol and N(G)-nitro-l-arginine methyl ester (l-NAME) were investigated. MAIN METHODS One hundred twenty-eight male Wistar rats were separated into 4 groups and subjected to occlusion of the superior mesenteric artery for 60 min. The Control group did not receive any substance before the surgical operation. However, the 3 other groups received the following: l-arginine (800 mg/kg body weight; l-Arg group), l-NAME (50mg/kg; l-NAME group) or allopurinol (100mg/kg; Allo group). Each substance was given by mouth in 3 equal doses 24, 12 and 1h before the surgical operation. Each group was then divided into 4 subgroups, which underwent different durations of reperfusion (0, 1, 8 or 24h). At the end of each time point, blood and tissue samples were collected, and histological examinations were performed. Serum nitrite and catalase, intestinal tissue myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) levels were determined. KEY FINDINGS At each reperfusion time point, the Allo group exhibited the mildest histological lesions in contrast to the l-NAME group, which showed the most severe lesions. MPO was decreased significantly in the Allo and l-Arg groups during reperfusion, and allopurinol administration caused earlier and stronger effect. iNOS and NT levels were higher in the l-Arg group and lower in the Allo group. Serum nitrite and catalase were increased in the l-NAME group after 24h. SIGNIFICANCE Oral administration of allopurinol exerted a strong and protective effect on the intestinal tissue that was subjected to I/R earlier than l-arginine. This finding was also supported with the MPO, iNOS and NT data.

DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

DNA topoisomerase IIα expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

Apoptotic markers for primary brain tumor prognosis

SummaryMolecular studies of brain tumors have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting clinical outcome and response to treatment. Quantitation of apoptosis by various techniques and the expression of several apoptotic markers have been studied in brain tumors, seeking to refine the information gained from established prognostic variables, which traditionally dictate therapeutic approaches. In the present review we discuss the role of the most extensively examined molecules involved in the apoptotic procedure, such as bcl-2, bax, fas/fasL, survivin and p53, as well as the incidence of baseline apoptosis in various brain tumors, in relation to prognosis. Summarizing current evidence, increased apoptosis and p53 genetic alterations have been advanced as adverse prognosticators in various types of central nervous system neoplasms, while bcl-2 expression appears to be deprived of any predictive value in primary brain tumors. The prognostic significance of the remaining apoptosis-related molecules remains controversial or too limited to draw any firm conclusions. The lack of unanimity of results mostly based on single-center retrospective studies underscores the necessity for large prospective randomized clinical trials, to elucidate the role of these molecular markers as determinants of clinical decision-making and as potential correlates of a pathobiologically tailored and individualized treatment strategy.

Evaluation of DNA topoisomerase IIα expression provides independent prognostic information in non‐Hodgkin's lymphomas

In view of the dual role that DNA topoisomerase IIa (TopoIIa) plays as a cell proliferation marker and as a possible indicator of chemosensitivity, we investigated its expression in non‐Hodgkins lymphomas (NHL) in relation to conventional clinicopathological parameters, cell proliferation (as defined by Ki67 immunoreactivity), response to therapy and patient outcome.

Expression of c-myc p62 Protein in Non-Hodgkin's Lymphomas

The expression of c-myc oncogene in neoplastic and non-neoplastic lymphoid tissue was studied using the specific monoclonal antibody myc 1-9E10 and the 3 step streptavidin-biotin immunoperoxidase method in paraffin sections. Twelve samples of non-neoplastic reactive lymph nodes of various etiology, 181 of non-Hodgkins lymphomas (NHL), and five of hairy cell leukemia (HCL) were studied. The staining pattern was mainly nuclear but cytoplasmic reactions were also occasionally observed. The percentage of positive cells per total, cell population was estimated and all cases were classified into four groups: 0.-15%, 16-.30%, 31-45% and more than 45% positive cells. In the reactive lymph nodes, mainly germinal center cells were stained, but the percentage in eleven of the 12 cases was less than 15%. All cases of HCL were negative. In NHL lymphoma, only malignant cells were evaluated. Fifty-six per cent of cases of NHL had more than 15% positive cells. The percentage of positive cells was greater in high grade than in intermediate and low grade NHL (80.6x, 47.6%, and 10.6 respectively had more than 30:< positive cells). This correlation proved to be statistically significant (p < 0.001). The above findings suggest a relation between the expression of the c-myc oncogene and lymphomagenesis and indicate that (evaluation of the expression of c-myc in NHL may be helpful in determining the grade of malignancy.

Hodgkin's lymphoma in first relapse following chemotherapy or combined modality therapy: analysis of outcome and prognostic factors after conventional salvage therapy.

Abstract: Objectives : To investigate the prognosis of patients with Hodgkins lymphoma (HL) who relapse following a complete remission (CR) achieved by chemotherapy with or without radiotherapy (CT±RT), and to identify prognostic factors for freedom from second progression (FF 2P). Methods: We analyzed the prognostic significance of the initial CT regimen (4 vs. 7–8 drugs), treatment‐free interval (TFI), and demographic, clinical, and laboratory factors at the time of relapse and diagnosis, in 113 patients with HL, who relapsed after a CR achieved by CT±RT. Results: Conventional salvage CT±RT was administered in 107 patients, while six received RT only. The 5‐yr FF2P was 24%, while the 10‐yr survival after relapse (O2S) was 39% and was not afffected by the initial CT regimen. Multivariate analysis revealed that extranodal disease at relapse (P<0.001), TFI<6 month (P<0.001), 5 involved sites at diagnosis (P=0.04) and anemia at relapse (P=0.03) were independent predictors of FF2P. 55% of patients had 0 or 1 of these adverse prognostic factors. The 5‐yr FF2P of patients with 0, 1 or 2 adverse factors was 58%, 34% and 5% (P<0.0001). The corresponding rates for 10‐yr O2S were 68%, 51% and 25%, respectively (P=0.002). Conclusions: Our data confirmed the significance of TFI and extranodal relapse and demonstrated a potential role for anemia at relapse and number of involved sites at diagnosis, for the prognosis of patients with HL relapsing after CT±RT. The combination of these prognostic factors defines a sizeable subgroup of patients with favorable outcome following conventional salvage therapy.

No evidence of splenic disease in patients with splenic marginal zone lymphoma undergoing splenectomy for autoimmune hemolytic anemia after monotherapy with rituximab.

Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterized by blood and bone marrow (BM) involvement associated with splenomegaly, while lymphadenopathy ...