Biomedical subjects
Publications and source records attributed to Sevasti Kamina.
Primary non-Hodgkin's lymphomas of the conjunctiva are uncommon. They are almost exclusively extranodal marginal zone B-cell lymphomas/mucosa-associated lymphoid tissue lymphomas. In this study, we report an extremely rare case of conjunctival mantle cell lymphoma in a 78-year-old man, presenting as a unilateral epibulbar mass.
We present the case of a 35-year-old man with Crohn's disease diagnosed at the age of 27, several months after an operation for small-bowel adenocarcinoma. Seven years after the adenocarcinoma diagnosis, the patient presented with severe continuous anal pain and diarrhea. In parallel with antibiotic administration, the patient was given treatment with Infliximab, but without clinical symptom amelioration. Sigmoidoscopy and subsequent biopsies from an ulcerated rectal area supported the diagnosis of Epstein-Barr virus-positive (EBV+) primary Hodgkin's lymphoma. Infliximab administration was immediately discontinued and the patient underwent oncological follow-up and began a course of chemotherapy. Only a few cases with primary gastrointestinal Hodgkin's lymphoma in Crohn's disease patients have so far been reported, including a variety of scenarios on the causal relationship including disease duration, presence of EBV, long-term immunosuppressive treatment and, recently, anti-TNFalpha administration.
The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10+/-/MUM1-/CD138-: 29 cases and bcl6-/CD10+/MUM1-/CD138-: two cases) and the nongerminal center B-cell-like profile (bcl6+/-/CD10-/MUM1+/CD138-); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=-0.536, P<0.001 and r=-0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=-0.276, P=0.014) and bid (r=-0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.
There is accumulating evidence that Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkin's and Reed-Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkin's and Reed-Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkin's and Reed-Sternberg cells.
We report an extremely rare case of intramural pregnancy with negative maternal b-HCG value. The patient underwent a "myomectomy" but the pathology examination revealed chorionic villi consistent with ectopic pregnancy. Diagnosis is very difficult in cases with menorrhagia and especially when pregnancy is not suspected.
BACKGROUND: Tumor angiogenesis is an absolute requirement for tumor growth and a prognostic factor for various malignant neoplasms. Recent reports in the literature have addressed the importance of the VEGF system in benign prostatic hyperplasia (BPH) and adenocarcinoma, however the results are controversial. The aim of the present study was to determine and compare the levels of VEGF expression and vascularity in BPH and prostate carcinoma. MATERIALS AND METHODS: We examined 60 prostate adenocarcinomas and 64 benign prostatic hyperplasias. Angiogenesis was estimated by determining microvessel counts (MVC), with the use of anti-CD31 and anti-CD34 antibodies. Expression of VEGF was also evaluated immunohistochemically. RESULTS AND CONCLUSION: Our data showed that angiogenesis was more prominent in carcinomas than in BPH. Furthermore, increased MVC was significantly associated with high-grade carcinomas. Angiogenesis was correlated with VEGF expression and it was, at least in part, mediated by the latter. Thus, prostate adenocarcinoma may represent a suitable neoplasm for antiangiogenic treatment in combination with conventional therapies.
BACKGROUND: There is evidence that apoptotic mechanisms mediated by bcl2 family proteins are involved in the pathogenesis of diffuse large B-cell lymphomas (DLBCL). In order to gain further insight into the apoptosis profile of DLBCL, 79 cases were investigated to determine whether distinct clusters of the combined expression levels of bcl2 family proteins can be identified in these lymphomas. MATERIALS AND METHODS: The combined immunohistochemical expression levels of the proteins bax, bak, bad, bid, bcl2 and bcl-xl were evaluated by cluster and discriminant analysis. The produced clusters were analyzed in relation to the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes. RESULTS: Cluster analysis produced: a) a low expression (69/79 cases) and a high expression pro-apoptotic cluster (10/79 cases) for the combined expression levels of the pro-apoptotic proteins bax, bak, bad and bid and b) a low expression (37/76 cases) and a high expression antiapoptotic cluster (39/76 cases) for the combined expression levels of anti-apoptotic proteins bcl2 and bcl-xl. The decreasing order of discriminant power for the percentages of tumor cells expressing pro-apoptotic and anti-apoptotic proteins was % bax + cells> % bak+ cells> % bid+ cells> % bad+ cells and % bcl2+ cells> % bcl-xl+ cells, respectively. The high expression pro-apoptotic cluster was significantly associated with higher mean values of Ki67 (p=0.047) and cyclin A (p=0.033) expression. The high expression pro-apoptotic cluster was significantly associated with the germinal center B-cell bc16/CD10/MUM1/CD138 differentiation immunophenotype (p=0.043). CONCLUSION: This study identified distinct clusters of DLBCL with respect to the combined expression levels of the apoptosis-associated bcl2 family proteins. These findings, taken together with our previous observations that distinct clusters with respect to the apoptotic index and the proliferation profile are identified in DLBCL, indicate that subgroups with distinct cellular kinetic properties can be defined in these lymphomas. The cluster analysis approach might be useful for the identification of subgroups of DLBCL with different clinical behavior since increased proliferation and apoptosis were reported to be associated with aggressive tumor behavior in these lymphomas.
Classical Hodgkin lymphomas (cHL) have now been recognized as B-cell lymphomas with some exceptional cases of T-cell origin. In recent years, there has been accumulating evidence that Hodgkin and Reed-Sternberg (H/RS) cells, the presumed neoplastic-cell population in cHL, are characterized by a profound disturbance of the cell cycle and apoptosis regulation. The constitutive activation of the nuclear factor (NF)-kappaB pathway, which is considered to be involved in the proliferation and survival of H/RS cells. Moreover, substantial evidence that H/RS cells have defective cell cycle and apoptosis regulation has been provided by studies showing that these cells are characterized, in a large proportion of cases, by alterations of the p53, Rb and p27 tumor suppressor pathways, overexpression of cyclins involved in the G1/S and G2/M transition such as cyclins E, D2, D3, A and B1, overexpression of cyclin-dependent kinases such as CDK1, 2 and 6 and overexpression of anti-apoptotic proteins such as c-FLIP, bcl-xl, c-IAP2, X-linked I4P and survivin. Recent studies suggest that interleukin 13 (IL-13) is an important growth and survival factor in H/RS cells. Furthermore, the Epstein-Barr Virus (EBV), which is present in H/RS cells in about 30-50% of cHL, has been shown to affect the cell cycle and apoptosis regulation in cHL. The present review summarizes data with respect to the cell cycle and apoptosis deregulation in cHL.
Diffuse large B-cell lymphomas (DLBCL) represent the most common type of adult non-Hodgkin's lymphomas in Western countries and are characterized by heterogeneous clinical, histological, immunophenotypic and genetic features. Recent investigations using cDNA and oligonucleotide microarrays have identified molecularly distinct groups of DLBCL with respect to the B-cell differentiation gene expression profile: the germinal center (GC) B-cell-like DLBCL, the activated B-cell-like DLBCL and the type 3 DLBCL. The GC B-cell-like DLBCL were characterized by the expression of genes of the normal GC B-cells, the activated B-cell-like DLBCL were characterized by the expression of genes that are normally induced luring in vitro activation of peripheral blood B-cells, while the type 3 DLBCL did not express either set of genes at a high level. Patients with GC B-cell-like DLBCL had more favorable clinical outcome than those with activated B-cell-like or type 3 DLBCL. Immunohistochemical studies have shown that the bc16/CD10/MUM1/CD138 B-cell differentiation immunophenotypes are prognostically relevant and may predict the cDNA classification in a sizable fraction of DLBCL. In the last few years, there has been accumulating molecular and immunohistochemical evidence indicating links between B-cell differentiation gene expression profiles and expression of apoptosis and cell cycle-associated genes in DLBCL. The present review summarizes data with respect to the relationships between B-cell differentiation, apoptosis and proliferation in DLBCL.