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A Batistatou

Publications and source records attributed to A Batistatou.

35 records · Page 2Linked to original sources
PubMed2004

Aggressive angiomyxoma of the vagina: a case report and review of the literature.

Aggressive angiomyxoma (AA) is a rare mesenchymal tumor of the lower pelvis and genital region, characterized by local infiltration and frequent, even multiple recurrences. In the present paper a case of a small-sized AA of the vagina, in a 55-year-old woman is reported. We describe the histological appearance and the immunohistochemical phenotype of this tumor and discuss its differential diagnosis from other mesenchymal lesions occurring in the pelvic and genital region. Furthermore, we attempt to enlighten the possible mechanisms that govern the pathogenesis and the biological behavior of this "mysterious" neoplasm.

Biopsy, Needle↗
PubMed2003

Activation of the JNK-AP-1 signal transduction pathway is associated with pathogenesis and progression of human osteosarcomas.

Osteosarcomas represent the most common primary malignant bone tumors; however, comprehension of the molecular mechanisms underlying their pathogenesis is far from thorough. Studies in cultured cells have demonstrated that the c-Jun N-terminal kinase (JNK) signal transduction pathway participates in the proliferation, differentiation, and apoptosis of osteoblasts. Phosphorylated JNKs activate the oncoprotein c-Jun, which is known to form the activator protein-1 (AP-1) transcription factor as a homo- or heterodimer. c-Jun's principal dimerization partner is c-Fos, which participates in the differentiation and function of osteoblasts and in the pathogenesis of osteosarcomas. A similar role for the JNK cascade in the malignant transformation of human osteoblasts and in the generation of osteosarcomas has not been documented. Our study addressed the possibility that a functional upregulation of the JNK pathway is implicated in the pathogenesis of osteosarcomas. To this end, we employed immunohistochemistry to examine normal bone and osteosarcoma cells in paraffin-embedded sections from 56 patients with high-grade tumors and 15 patients with low-grade tumors. We assessed the protein levels of the two major JNK isoforms (JNK1 and JNK2); their phosphorylated-hence activated-species, p-JNK; their substrate, c- Jun; its phosphorylated (activated) form, pc-Jun; and c-Jun's heterodimeric partner, c-Fos. We also examined the immunohistochemical profile of the alpha chain of the nascent polypeptide-associated complex (alpha-NAC), an osteoblast-specific AP-1 coactivator that potentiates the transcriptional activity of the c-Jun/c-Jun homodimer. Positive immunostaining for JNK1, JNK2, p-JNK, c-Jun, pc-Jun, c-Fos, and alpha-NAC was observed in 86, 93, 94, 99, 97, 99, and 97.5% of the samples, respectively, whereas normal bone was devoid of these immunoreactivities. The cellular levels of all proteins were significantly correlated to each other (P < 0.001 for each correlation). Moreover, significantly higher expression levels of all proteins were detected in high-grade tumors compared to levels in low-grade ones. The observed expression profile of alpha-NAC implies that the active AP-1 in human osteosarcomas most likely comprises c-Jun/c-Jun homodimers. When cellular levels of the JNK pathway components and c-Fos were evaluated as possible biological markers of tumor grade, high expression of c-Jun and abundant pc-Jun predicted a high-grade tumor. Our findings provide novel evidence that the JNK signaling pathway is functionally operative in the malignant transformation of osteoblasts and the subsequent development and progression of human osteosarcomas. Evaluation of c-Jun expression and JNK-dependent activation may facilitate an improved prediction of the tumor's clinical behavior and potentially be exploited in designing patient-tailored treatment regimens.

Adolescent↗
PubMed2003

Immunohistochemical expression of glucose transporter Glut1 and cyclin D1 in breast carcinomas with negative lymph nodes.

All malignant cells appear to have increased needs for glucose in vitro as well as in vivo. The enhanced glucose uptake is mediated through transporters (Gluts), whose action and expression are regulated by oncogenes and growth factors. Cyclin D1 is a nuclear protein that plays an important role in regulating the cell cycle by promoting entry of cells from the G1 to S phase. Increased expression of Glut1 glucose transporter and cyclin D1 have been reported in several neoplasms. In the present study we examined the expression of Glut1 and cyclin D1 in breast carcinomas with negative lymph nodes. We studied 78 infiltrating ductal carcinomas (25 grade 1, 36 grade 2, and 17 grade 3) with negative lymph nodes. Glut1 was expressed in 28% of grade 1, 63.8% of grade 2 and 58.7% of grade 3 carcinomas. Nuclear expression of cyclin D1 was detected in 32% of grade 1, 44.4% of grade 2, and 41.2% of grade 3 carcinomas. From our study it appears that in breast carcinomas with negative lymph nodes Glut1 expression is better correlated to the grade of the neoplasm than cyclin D1.

Biomarkers, Tumor↗
PubMed2001

S-100 protein-positive dendritic cells and CD34-positive dendritic interstitial cells in palatine tonsils.

Dendritic cells (DCs) are effective antigen-presenting cells and have been shown to mature from precursor CD34-positive stromal cells (dendritic interstitial cells, DICs) or monocytes. To gain insight into the local immune response in human tonsils, we investigated immunohistochemically the presence of DCs and DICs in 17 non-hyperplastic and 13 hyperplastic tonsils. Dense infiltrates of S-100-positive DCs were noted in the majority of hyperplastic tonsils, while there were fewer in non-hyperplastic tonsils. DICs were noted specifically at the periphery in the dense hemi-capsule cap that separates the tonsil from the underlying muscle. In addition, their small number suggests that the accumulation of S-100 dendritic cells in hyperplastic palatine tonsils is achieved through migration from other sites rather than through maturation from precursors locally.

Adult↗
PubMed1993

Internucleosomal DNA cleavage and neuronal cell survival/death.

Serum-free PC12 cell cultures have been used to study the mechanisms of neuronal death after neurotrophic factor deprivation. We previously reported that PC12 cells undergo "apoptotic" internucleosomal DNA cleavage after withdrawal of trophic support. Here, we have used a sensitive method to detect PC12 cell DNA fragmentation within three hrs of serum removal and have exploited this assay to examine several aspects regarding the mechanisms of neuronal survival/death. Major advantages of this assay are that it permits acute experiments to be performed well before other manifest signs of cell death and under conditions that cannot be applied chronically. We find that this apopotic DNA fragmentation is distinct from the random DNA degradation that occurs during necrotic death. Major observations include the following: (a) There is a good correlation between the ability of trophic substances to promote PC12 cell survival and to inhibit early DNA fragmentation. (b) Phorbol ester, an activator of PKC, acutely suppresses DNA fragmentation, but does not promote long-term survival or inhibition of endonuclease activity when applied chronically due to its downregulation of PKC. (c) Cells undergoing apoptosis within 3 h of serum withdrawal have a "commitment point" of only 1.0-1.5 h beyond which they can no longer be rescued by NGF. (d) Aurin, a non-carboxylic analog of the endonuclease inhibitor ATA, also inhibits DNA fragmentation and promotes short-term survival of PC12 cells. (e) Macromolecular synthesis is not required for DNA fragmentation or for NGF to prevent this event. (f) Extracellular Ca2+ is not required for internucleosomal DNA cleavage caused by serum withdrawal or for suppression of this by NGF. (g) DNA fragmentation can also be detected in cultures of rat sympathetic neurons as early as 10 h after removal of NGF. As in PC12 cell cultures, this precedes morphological signs of cell death.

Animals↗
PubMed1993

Bcl-2 affects survival but not neuronal differentiation of PC12 cells.

Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the mechanisms of neuronal death after neurotrophic factor deprivation. These cultures, as well as NGF-deprived cultures of sympathetic neurons, manifest and endonuclease activity that leads to "apoptotic" internucleosomal DNA cleavage. Overexpression of the proto-oncogene bcl-2 blocks apoptotic death in various cell types. To study the actions of this protein in neuronal cells, we derived PC12 cell lines stably transfected with a cDNA encoding human bcl-2. It is reported here that lines expressing high levels of the exogenous bcl-2 protein are protected from both death and apoptotic DNA fragmentation caused by removal of trophic support. However, expression of high levels of exogenous bcl-2 neither mimics nor interferes with promotion of neurite outgrowth by NGF.

Animals↗
PubMed1993

Gangliosides rescue neuronal cells from death after trophic factor deprivation.

Serum-free cultures of PC 12 cells have been used as a model system for studying neuronal death occurring after neurotrophic factor deprivation. In this system, NGF rescues cells from death and prevents apoptotic DNA fragmentation. We report here that GM1 also promotes long-term survival of naive and NGF-pretreated PC 12 cells in serum-free medium and prevents internucleosomal cleavage of PC 12 cell DNA. In contrast to NGF, GM1 does not promote neurite outgrowth or somatic hypertrophy. The survival effects of GM1 are concentration dependent, with maximal activity at 30-50 microM. Optimal promotion of survival is obtained with multiple additions of GM1. Asialo-GM1 and sialic acid do not mimic these actions, indicating a requirement for the intact GM1 molecule. Prevention of serum-free PC 12 cell death is also obtained with di-, tri-, and tetrasialogangliosides. The ganglioside effects on survival and DNA fragmentation appear to be independent of macromolecular synthesis. GM1 is also effective under conditions in which cellular protein kinase C activity is downregulated by preexposure to high concentration of 12-O-tetradecanoylphorbol-13-acetate. Furthermore, GM1 promotes long-term survival of cultured rat sympathetic neurons after withdrawal of NGF. These findings complement prior observations that gangliosides protect cerebellar granule neurons from neurotoxicity caused by exposure to excitatory amino acids and extend the actions of gangliosides to rescue of neuronal cells deprived of neurotrophic factor support.

Animals↗
PubMed1992

Nerve growth factor employs multiple pathways to induce primary response genes in PC12 cells.

Nerve growth factor (NGF) leads to neuronal differentiation of PC12 cells and promotes their survival in serum-free medium. Past studies have shown that purine analogues block some of the effects of NGF but not others and thus that they can be used to dissect the mechanistic pathways of its action. In the present work we used 2-aminopurine (2-AP) and 6-thioguanine (6-TG) to examine whether NGF causes activation of primary response genes through a single signaling pathway or via multiple pathways. Northern blot analysis and nuclear run-off transcription assays were used to assess the activation of c-fos, c-jun, TIS1, TIS8, and TIS11 after exposure of PC12 cells to NGF in the presence or absence of 2-AP and 6-TG. Our findings indicate that NGF appears to employ at least three distinct pathways to induce early genes in PC12 cells. This suggests that the NGF signaling mechanism diverges at an early point after interaction of NGF with its receptor.

2-Aminopurine↗
PubMed1991

Aurintricarboxylic acid rescues PC12 cells and sympathetic neurons from cell death caused by nerve growth factor deprivation: correlation with suppression of endonuclease activity.

Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the neuronal cell death which occurs after neurotrophic factor deprivation. In this experimental paradigm, nerve growth factor (NGF) rescues the cells from death. It is reported here that serum-deprived PC12 cells manifest an endonuclease activity that leads to internucleosomal cleavage of their cellular DNA. This activity is detected within 3 h of serum withdrawal and several hours before any morphological sign of cell degeneration or death. NGF and serum, which promote survival of the cells, inhibit the DNA fragmentation. Aurintricarboxylic acid (ATA), a general inhibitor of nucleases in vitro, suppresses the endonuclease activity and promotes long-term survival of PC12 cells in serum-free cultures. This effect appears to be independent of macromolecular synthesis. In addition, ATA promotes long-term survival of cultured sympathetic neurons after NGF withdrawal. ATA neither promotes nor maintains neurite outgrowth. It is hypothesized that the activation of an endogenous endonuclease could be responsible for neuronal cell death after neurotrophic factor deprivation and that growth factors could promote survival by leading to inhibition of constitutively present endonucleases.

Animals↗
PubMedDate not supplied

Integrins in head and neck squamous cell carcinoma (HNSCC): a review of the current literature.

Integrins are a family of adhesion molecules performing a major role in multiple cellular functions. Their contribution in carcinogenesis and metastatic process are the object of intense research activity worldwide during the last decades. This review focuses on the existing knowledge about integrin expression in head and neck squamous cell carcinoma (HNSCC) as it has been acquired mainly by immunohistochemical methods and by in vitro assays. The elucidation of the exact role of integrins and the study of expressive alterations of these molecules in cancer cells, may result in novel therapeutical approaches for useful applications in the clinical routine of HNSCC in the future.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Tumor markers in cancer patients. an update of their prognostic significance. Part II.

The primary determinant of outcome in patients with cancer is the development of distant metastasis. Metastasis is a multistep process involving disruption of cell-matrix adhesion, dissolution of the extracellular matrix, angiogenesis, invasion in the blood vessel wall, extravasation and establishment of a secondary growth. Nowadays, a large number of biochemical and cell biological studies have indicated the important role of extacellular matrix adhesion molecules, proteinases and angiogenic factors in the dissemination of cancer. Cell adhesion molecules, such as integrins, E-cadherin, catenins and CD44 appear to have some prognostic significance, especially in gastric, colorectal and lung cancer patients. Since matrix degrading proteinases are involved in cancer spread, they should be good candidates as prognostic factors. The proteinase which has been investigated in greatest detail is uPA in breast cancer. As a marker of cancer, its main value is to aid in selecting the subgroups of node-negative breast cancer patients that are unlikely to benefit from adjuvant chemotherapy. Cathepsin D and metalloproteinases (MMPs) look promising prognostic markers but further work is needed to establish their utility. Intratumoral angiogenesis is a putative prognostic indicator for some types of cancer. High expression of the angiogenic factor VEGF is associated with angiogenesis and an unfavourable survival.

Biomarkers, Tumor↗
PubMedDate not supplied

Nuclear grooves in fine needle aspiration (FNA) biopsies of breast lesions.

The present study was undertaken to evaluate the significance of grooved nuclei as an additional diagnostic criterion for primary breast carcinoma as well as their association with tumor grade in cytologic material obtained by fine needle aspiration (FNA). Cytologic slides of 105 cases of breast carcinoma (89 ductal, 10 lobular, 3 medullary, 3 mucinous) and 39 cases of benign lesions were reviewed. Histologic confirmation was obtained in all cases. In each case the number of grooved nuclei per 200 well-preserved cells per slide was recorded. Nuclear grooves were found in 62% (65/105) of the malignant and in 36% (14/39) of the benign lesions. This cytomorphologic feature was observed in all histologic types of breast carcinoma. Furthermore, nuclear grooves were present in all grades of ductal carcinoma, and at about the same frequency. Our findings indicate that in the mammary gland nuclear grooving cannot be considered as a criterion of malignancy, and is not helpful either in differentiating the various histologic types or in grading breast tumors in FNA preparations.

Adolescent↗