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L Kaklamanis

Publications and source records attributed to L Kaklamanis.

At least 19 recordsLinked to original sources
PubMed2001

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia.

OBJECTIVE: Promoting angiogenesis may be an effective treatment for patients with diffuse peripheral vascular disease. This study investigated whether estrogen can promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia. METHODS AND RESULTS: Ischemia was induced in one hindlimb of 24 oophorectomized New Zealand White rabbits. Ten days later (day 0), they were randomized into 4 groups for intramuscular treatment in the ischemic limb: controls receiving saline at day 0; Estrogen-1 group receiving estradiol valerate, modified release (EVMR), 1 mg/kg at day 0; Estrogen-2 group receiving EVMR 1 mg/kg at days 0 and 15; and Estrogen-3 group receiving EVMR 2 mg/kg at day 0. Revascularization was evaluated by clinical indexes, such as ischemic/normal limb systolic blood pressure (BPR), and capillary density/muscle fiber in the abductor muscle of the ischemic limb at the time of death (day 30). At day 30 the BPR was increased in all groups (0.39+/-0.08 in the controls, 0.52+/-0.11 in the Estrogen-1 group, 0.65+/-0.13 in the Estrogen-2 group and 0.61+/-0.16 in the Estrogen-3 group, F=2.39, P=0.04). The capillary/muscle fiber at day 30 was 0.87+/-0.09, 1.08+/-0.15, 1.01+/-0.14 and 1.10+/-0.9 (F=5.01, P=0.01), respectively, in the 4 groups. The capillary/muscle fiber was related to BPR (r=0.48, P<0.02) and to 17-beta estradiol plasma levels of day 15 (r=0.58, P=0.003) and of day 30 (r=0.46, P<0.02). CONCLUSION: Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.

Animals↗
PubMed2001

[A voluminous vascular leiomyoma of the pancreas treated by personal technique of resection of the pancreatic head without duodenectomy].

A new technique variation of complete resection of the pancreatic head with preservation of the duodenum is described. The steps of this intervention are the partial mobilization of the duodenum, the mobilization of the gastric antrum, the section of the pancreatic neck and the complete resection of the pancreatic head with a meticulous dissection/section of the small blood vessels connecting the duodenum and the head of the pancreas. The terminal part of choledochus is removed with the specimen of the pancreas. The intervention is completed with cholecystectomy, end-to-side pancreaticojejunostomy, end-to-side choledocho-jejunostomy and side-to-side jejunojejunal anastomosis. The authors carried out this intervention on a 74-year old woman with a voluminous vascular leiomyoma of the pancreatic head. The patient, two years after the operation, is well with a normal clinical and laboratory follow-up.

Aged↗
PubMed2000

Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits.

BACKGROUND: Hypercholesterolemia predisposes to coronary artery disease and causes endothelial dysfunction; some reports suggest that endothelial derived substances are involved in ischemic preconditioning. OBJECTIVE: Our aim was to examine the possibility that preconditioning maybe attenuated in a clinically relevant animal model of hypercholesterolemia with atherosclerosis. METHODS: Male rabbits were fed with cholesterol enriched diet and then divided into two groups (A and B) without and with preconditioning, respectively. A second series of rabbits fed a normal diet were similarly divided into two groups (C and D) without and with preconditioning, respectively. All the animals were subjected to 30 min ischemia and 180 min reperfusion. Blood samples were collected for cholesterol assessment; arterial and heart samples were harvested at the end for histopathological examination. Infarct (I) and risk areas (R) were delineated with Zn-Cd particles and TTC staining. RESULTS: Cholesterol in groups A and B was 58.3+/-8.7 mg% at baseline and 1402+/-125 mg% at 8 weeks (P<0.0001) and in groups C and D 57.5+/-5.8 mg% before the surgical procedure. I/R% was 39. 3+/-6.3% in group A, 16.7+/-3.9% in B (P<0.01), 41.4+/-7.5% in C and 10.8+/-3.3% in D (P<0.01). CONCLUSION: We conclude that preconditioning is unlikely to be attenuated by hypercholesterolemia.

Animals↗
PubMed2000

c-erbB-2 and episialin challenge host immune response by HLA class I expression in human non-small-cell lung cancer.

The role of major histocompatibility complex expression in cancer prognosis and pathogenesis is contradictory. The aim of the current study was to compare the expression of HLA class I molecules and of oncoproteins that may be sources of peptides presented by HLA class I antigens in non-small-cell lung cancer. For this purpose, the expression of HLA class I antigen and TAP-1 molecule (a transporter in the antigen-processing 1 transport protein) were studied with epidermal growth factor, receptor; c-erbB-2; episialin; wild-type and mutant p53; bcl-2 oncoprotein expression; and angiogenic factor expression (vascular endothelial growth factor and thymidine phosphorylase). The degree of lymphocytic stromal infiltration and of platelet-endothelial cell adhesion molecule-expressing lymphocytes was also studied. A strong association of c-erbB-2 and MUC1 (episialin) expression with HLA class I expression was observed (p = 0.005 and 0.009, respectively). Intense CD31-positive lymphocytic infiltration was also more frequent in HLA class I-positive cases (p = 0.05). Although there was no association of HLA class I expression with survival, loss of the HLA class I expression in MUC1 or c-erbB-2 overexpressing cases conferred a poorer clinical outcome (p = 0.04). Both c-erbB-2 and MUC1 are well-known targets of T-cell-mediated cytotoxicity and cell-cell or cell-matrix adhesion-regulating proteins. The authors provide evidence that the sequence of cell adhesion-disrupting oncoprotein expression, HLA class I induction, and enhanced epitope presentation followed by lymphocytic response is an important pathogenetic three-step sequence of events that define, in part, the clinical outcome in non-small-cell lung cancer.

Aged↗
PubMed1999

Nuclear localization of human AP endonuclease 1 (HAP1/Ref-1) associates with prognosis in early operable non-small cell lung cancer (NSCLC).

The present study examined the immunohistochemical expression of human AP endonuclease 1 (HAP1/Ref-1), the major endonuclease in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA, in normal lung and lung carcinomas. Cellular expression of HAP1 was determined using a standard avidin-biotin-peroxidase complex (ABC) technique and an anti-HAP1 rabbit polyclonal antibody on paraffin-embedded tissue sections from normal lung and in 103 primary non-small cell lung carcinomas (NSCLCs). In normal lung, the staining for HAP1 was found to be both nuclear and cytoplasmic in the pneumocytes of the alveoli. Superficial ciliated cells of the bronchial epithelium presented cytoplasmic staining, while staining for the basal cells was mostly nuclear. Bronchial glandular cells demonstrated mixed nuclear and cytoplasmic staining. Lung carcinomas showed all patterns of expression for HAP1. Loss of HAP1 expression was associated with low proliferation index (p=0.01) and with squamous histology (p=0.04). In squamous carcinomas, a significant correlation was observed between positive nuclear HAP1 and negative p53 expression (p=0.03). A survival benefit was seen in patients presenting nuclear HAP1 expression and those presenting the nuclear HAP1+/p53- phenotype (p=0.01 and 0.007, respectively). It is concluded that nuclear HAP1 localization may be relevant to its role as a DNA repair protein and/or to the recently proposed role as an activator of wild-type p53, and thus to the better outcome seen in this group of patients.

Aged↗
PubMed1999

Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer.

Defects in the APC-beta-catenin pathway are common in colon cancer. We investigated whether aberrant regulation of upstream ligands stimulating this pathway occur in colon cancer. Using RNAase protection analysis, six out of eight wnt genes were expressed in 14 matched cases of normal, adenomatous and malignant colorectal tissues. Wnt 2 and wnt 5a were significantly up-regulated in the progression from normal through adenoma to carcinoma. Transcripts for wnts 4, 7b, 10b and 13, but not wnt 2 and wnt 5a were detected in several colorectal cell lines. In situ hybridization demonstrated that wnt 2 and wnt 5a transcripts were mainly in the lamina propria/stroma region with labelling predominantly in macrophages. Immunostaining with CD68 confirmed the wnt-expressing cells as macrophages. These results show a major difference in wnt expression in colon cancer compared to colon adenomas and suggest stromal wnt expression may play a role in tumour progression.

Adenocarcinoma↗
PubMed1998

Expression of apoptotic and proliferation markers in meningiomas.

Fifty-two intracranial, totally excised meningiomas were immunohistochemically analysed for the expression of bcl-2 and p53 proteins, in parallel with the assessment of the proliferating cell nuclear antigen labelling index (PCNA LI) and the mitotic index (MI). bcl-2 was expressed in 26.8 per cent and p53 in 32.6 per cent of the tumours, exhibiting a similar staining pattern, with low levels of immunoreactive cells. The bcl-2-positive/p53-negative subgroup showed a significant association with a benign histological pattern. Expression of bcl-2 appeared to have no influence on the rate of recurrence; p53 expression was the only factor with prognostic significance for recurrence (p = 0.10). There was no interaction between bcl-2 and p53 expression. The PCNA LI was correlated with the MI and the grade of malignancy, proving to be a useful proliferation marker and an additional indicator of the more anaplastic histological patterns in meningiomas. Proliferation indices appeared to have no correlation with the recurrence rate of totally resected tumours. Meningiomas expressing the bcl-2 protein presented a high proportion of proliferating cells in S phase. In contrast, all the tumours which recurred had a minimal S-fraction of proliferating nuclei. These findings may improve our understanding of the interaction between cell proliferation, expression of apoptotic markers, and recurrence in meningiomas.

Adult↗
PubMed1998

Neoplastic stroma and epithelium show up-regulation of platelet-derived endothelial cell growth factor/thymidine phosphorylase in colorectal carcinomas but not adenomas.

Tumor angiogenesis, a crucial step in tumor growth and progression, is regulated by an increasing number of angiogenic factors. One of those is platelet-derived endothelial cell growth factor, recently shown to bethymidine phosphorylase (TP), which reversibly catalyzes the phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. TP overexpression in tumors has been reported, but the differential expression of this enzyme in the colorectal adenoma-carcinoma sequence has not been examined in detail. In this study we analyzed 16 hyperplastic polyps, 37 solitary tubular and tubulovillous adenomas (ranging from 1 to 7.5cm, median 3.2cm), and 47 cases of colorectal carcinomas arising on the basis of pre-existing adenomas (25 cases were Dukes' A, 10 Dukes' B and 12 Dukes' C). Non-neoplastic colonic mucosa was also examined separately from all the above carcinoma cases. All samples were stained for TP and assessed for vascularity. Normal mucosa, hyperplastic polyps, and all but three adenomas and the adenomatous parts of the invading tumors did not show any epithelial cell positivity, and only occasional macrophages and fibroblasts showed weak cytoplasmic immunoreactivity for TP. Neoplastic cells in the carcinomatous part of the tumors were positive for TP in 18 out of 47 (36%) cases. Both nuclear and cytoplasmic staining was detected but in a few cases only one of these was present. There was a highly significant difference between TP expression in neoplastic epithelial cells in adenomas compared with carcinomas (p=0.0001). The same was true when the immunoreactivity of the stromal cells was compared (p=0.0001). Areas with high angiogenesis such as those at the invading edge of the tumor showed intense epithelial, endothelial and stromal TP immunoreactivity. These results show up-regulation of a major angiogenic pathway in both the tumor epithelium and stromal cells with progression from adenoma to carcinoma, and suggest TP may be a candidate target for therapy.

Journal Article↗
PubMed1998

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis.

Human AP endonuclease (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemistry to examine the expression of HAP1 in normal breast and in 102 primary breast carcinomas. In normal breast epithelium, HAP1 had a uniformly nuclear localization. However, in lactating glandular epithelium, the expression of HAP1 was predominantly cytoplasmic. In carcinomas, both nuclear and cytoplasmic (44%), cytoplasmic (28%) or nuclear staining (24%) were observed. In four cases (4%), no HAP1 expression was detected. All patterns of expression for HAP1 were demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were usually accompanied by mostly cytoplasmic staining. Similarly, the HAP1 expression in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear HAP1 expression was significantly correlated with low angiogenesis (P = 0.007) and negative lymph node status (P = 0.001). In contrast, cases with cytoplasmic as well as nuclear staining were associated with poor prognostic factors, such as high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear staining may be related to better differentiation, as in normal breast, and hence better prognostic features, and cytoplasmic staining to a more metabolically active phenotype with high protein synthesis, as in lactating breast.

Adult↗
PubMed1998

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer.

Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB DO7), and 41 of these 144 p53-positive cases were also bcl-2 positive (28%) compared with 32 of the remaining 80 p53-negative cases (40%). Survival was significantly worse (P = 0.01) in the p53-positive cases. Bcl-2-positive cases, including patients in all Dukes' stages, had a slightly better prognosis which was not statistically significant. However, cases at an early stage (Dukes' stages A and B) and with negative p53 status, had a much better prognosis if they showed bcl-2 protein expression, suggesting that the bcl-2 status itself has an effect on prognosis (P = 0.01). Neither bcl-2 nor p53 alone was correlated with stage, but when examined by both p53 and bcl-2 status a group [bcl-2(+)/p53(-)] with better prognosis was defined. The last group was significantly lower Dukes' stage, with 26 out of 32 cases (81%) being A or B compared with 22 (11%) of the 202 remaining cases (P = 0.004). Thus, either loss of bcl-2 expression or gain of abnormal p53 expression is associated with high stage and poor prognosis. The bcl-2(+)/p53(-) phenotype is similar to that of normal mucosa, and these results suggest that such cases represent an indolent group at an early stage in the progression of colorectal cancer.

Adult↗
PubMed1998

Expression and subcellular localization of human AP endonuclease 1 (HAP1/Ref-1) protein: a basis for its role in human disease.

AIMS: Human AP endonuclease 1 (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA by catalysing hydrolytic cleavage of the phosphodiester backbone 5' to the site. HAP1 is also known to be a potent reduction-oxidation (redox) factor, regulating the binding activity of a number of transcription factors. The purpose of the present study was to examine the expression of HAP-1 in a wide range of human tissues. METHODS AND RESULTS: Using a recently developed specific rabbit polyclonal antibody, we performed immunohistochemistry on paraffin-embedded tissue material. Nuclear staining was detected in crypt cells of the small and large intestine, epithelial cells of breast ducts, basal cells of the skin, alveolar cells of the lung, lymphocytes of the marginal zone of the spleen, in the surface epithelium and stromal cells of the ovary and the transitional epithelium of the bladder. Unexpectedly for a presumed nuclear protein, the staining pattern in some cell populations was mainly cytoplasmic (e.g. superficial cells of gastrointestinal tract, Langerhans cells, Leydig cells and spermatocytes, epithelium of the prostate glands), or both cytoplasmic and nuclear (e.g. epithelial cells of thymus, follicular thyroid cells, parietal cells of the stomach, glandular epithelial cells of the cervix, epithelial cells of exocrine pancreas). CONCLUSION: This differential expression in a wide spectrum of cells is indicative of a potential multifunctional action of HAP1, not necessarily restricted to a role in the nucleus.

Antibodies↗
PubMed1997

cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas.

dishevelled (Dsh) is a member of the segment polarity gene family in Drosophila which plays an important role in the early developmental patterning processes. A human homologue of Dsh (DVL-1) has recently been described. Here, we report the cloning of a second human homologue of Dsh (called DVL-3) by cDNA library screening. The human DVL-3 gene encodes a predicted 716 amino acid protein which exhibits 98% amino acid identity with mouse Dvl-3 and 49% with Drosophila Dsh. DVL-3 was mapped to 3q27. The expression of DVL-3 mRNA was detected in 30 human cell lines and 2 primary cell cultures. DVL-3 mRNA was detected in normal human breast tissues (n = 4) and tumours (n = 25). Statistically, there was no difference in DVL-3 mRNA level between normal breast tissues and tumours. In human colorectal samples, DVL-3 was expressed equally in matched normal tissues, polyps and tumours. The data indicates that DVL-3 is widely expressed in human cells and supports the notion of a new developmental gene family for dishevelled which may have a widespread role in signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Human apurinic endonuclease 1 expression in a colorectal adenoma-carcinoma sequence.

Human apurinic endonuclease 1 (HAP1) plays a key role in the repair of baseless sites in DNA. HAP1 is also known to be a potent regulator of the binding activity of a number of transcription factors. We have examined the immunohistochemical expression of the HAP1 protein in normal colorectal mucosa, hyperplastic polyps, tubulovillous adenomas, and carcinomas. In normal colonic mucosa, the predominant staining was nuclear in the less differentiated cells located at the lower part of the crypt, but it was cytoplasmic in the more differentiated superficial colonic epithelium. HAP1 expression was nuclear in 3 of 30 adenomas (10%) and 5 of 44 carcinomas (11%), but it was cytoplasmic in 11 of 30 adenomas (37%) and 22 of 44 carcinomas (50%) and both nuclear and cytoplasmic in 16 of 30 adenomas (53%) and 17 of 44 carcinomas (39%). The observed staining in stromal fibroblasts and endothelial cells was nuclear, whereas that in macrophages was cytoplasmic. Our data indicate that HAP1 is expressed in different subcellular compartments during normal differentiation and that this pattern is disrupted in adenomas and carcinomas. The differential localization may be relevant to the two different proposed functions of HAP1.

Adenocarcinoma↗
PubMed1997

The epidemiologic profile of Kaposi's sarcoma in Greece prior to and during the AIDS era.

To determine the incidence rates and to describe the epidemiological patterns of non-AIDS Kaposi's sarcoma in the central southern area of Greece during the period 1974-1989, all 473 incidence cases reported to Pathology Departments were studied. The mean age (SD) was 67.6 (12.9) years among 297 males and 66.1 (15.9) years among 176 females. The mean age-standardized (Greek population 1981) incidence rate was 0.47 cases per 100,000 total population per year (males 0.62, females 0.32). The standardized incidence rates increased over time for males, with the incidence-rate ratios relative to the earliest period, 1974-1978, being 1.44 (95% CI, 1.02-2.04) for the 1979-1983 interval and 2.12 (95% CI, 1.55-2.90) for the 1984-1989 interval. However, the rates for females did not show a similar pattern. The age-adjusted male:female ratio was 1.6 in 1974-1983 and 2.6 in 1984-1989. Poisson-regression modelling suggested a shift in the age-specific incidence rate in men, towards younger ages during the last period, 1984-1989.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Platelet-derived endothelial cell growth factor (thymidine phosphorylase) expression in lung cancer.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is an enzyme with angiogenic and cell motility properties. Moreover, it is involved in the transformation of fluoropyrimidines into active cytotoxic metabolites. In the present study, the expression of PD-ECGF in normal lung and lung cancer was immunohistochemically evaluated using the P-GF.44C monoclonal antibody. Alveolar and tumoural macrophages were invariably stained and were used as an internal control for assessment of the staining. Alveolar epithelium was always negative, whilst bronchiolar epithelium showed occasional positive reactivity. Normal lung and tumour endothelium was occasionally positive. Positive staining in more than 50 per cent of cells was observed in 23/71 squamous carcinomas (32 per cent), 16/38 (42 per cent) adenocarcinomas, and 2/6 (33 per cent) adenosquamous carcinomas. Differentiated areas and areas of squamous metaplasia were more strongly positive than other tumour areas. All 22 small cell carcinomas and one carcinoid tumour were negative. The present study provides a baseline for future studies in non-small cell lung cancer to correlate PD-ECGF expression with tumour vascularization, prognosis, and response to chemotherapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Selection for beta 2-microglobulin mutation in mismatch repair-defective colorectal carcinomas.

Novel peptide antigens complexed with human leukocyte antigen (HLA) and beta 2-microglobulin (beta 2M) molecules are presented at the cell surface to cytotoxic T lymphocytes (CTLs), provoking lysis of the antigen-presenting cell [1]. In tumor cells, genetically altered or abnormally expressed proteins provide a source of peptides that can be presented to CTLs; the resulting anti-tumour CTL responses may provide part of the body's defence against cancer. Disabling mutations in the HLA and beta 2M proteins required for peptide presentation allow a tumour cell to escape destruction by CTLs. Cells with deficient DNA mismatch repair have high spontaneous mutation rates [2] and produce many altered proteins that are a potential source of numerous unique peptides. Mutator tumour cells might therefore be particularly vulnerable to immune surveillance and CTL attack. Mutator phenotypes [3,4] and loss of beta 2M (or HLA) expression [5,6] are both relatively common among sporadic colorectal tumours. We have compared the frequency of beta 2M mutations in sporadic colorectal and other tumours with and without a mutator phenotype. Mutations were more frequent among colorectal tumours with the microsatellite instability indicative of a defect in DNA mismatch repair. The inactivating beta 2M mutations were predominantly frameshifts, which is consistent with the underlying mismatch repair defects. Evasion of immune surveillance by acquiring beta 2M mutations therefore occurs at high frequency in tumour cells with a mutator phenotype due to defective DNA mismatch repair.

Colorectal Neoplasms↗
PubMed1996

Detection of p53 in Hodgkin's disease using the monoclonal antibody PAb248.

The recent demonstration that the murine anti-p53 monoclonal antibody PAb248 can identify human p53 in a variety of normal tissues proves that immunohistochemical detection does not necessarily indicate the presence of mutations. PAb248 can detect p53 protein in a cytoplasmic-perinuclear localization, not previously described. The present study presents the expression of this antibody in a series of 34 cases of Hodgkin's disease, comparing it with the antibodies CM1, PAb1801, and PAb240. In all cases, PAb248 showed uniform cytoplasmic-perinuclear staining in small and medium-sized lymphocytes, while it was constantly negative in Hodgkin, Reed-Sternberg (R-S/H) cells, and variants. This pattern of staining was the opposite to that observed with the antibodies CM1, PAb1801, and PAb240, where the staining was nuclear and restricted to the R-S/H cells, with the small lymphocytes being negative. p53 can be found in different conformations and localizations, with the cytoplasmic-perinuclear localization mainly, although not exclusively, being found in normal and reactive tissues and the nuclear localization being mainly expressed by neoplastic cells. These results give further support to the theory that the R-S/H cells are the neoplastic population in Hodgkin's disease, while the surrounding lymphocytes are reactive.

Antibodies, Monoclonal↗