Biomedical subjects

E Sivridis

Publications and source records attributed to E Sivridis.

At least 73 records · Page 4Linked to original sources

PubMed2000

Tumor specific activation of the VEGF/KDR angiogenic pathway in a subset of locally advanced squamous cell head and neck carcinomas.

Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and flk-1(KDR), constitute an important angiogenic pathway which, under hypoxic conditions, is up-regulated in many solid tumours. We used the monoclonal antibody 11B5, specific for recognizing VEGF expression and the 'VEGF/flk-1(KDR) complex' on tumour endothelium, to assess free VEGF protein expression and VEGF/receptor activated microvessel density (aMVD) in a series of 104 inoperable locally advanced squamous cell carcinomas of the head and neck, treated with chemo-radiotherapy. High VEGF expression in cancer cells was strongly associated with high VEGF/receptor expression in the vasculature. The high VEGF expression and the aMVD were not associated with the standard microvessel density (sMVD), as assessed with the monoclonal antibody anti-CD31 and, were not detected in normal tissue. An increased sMVD, however, was significantly related with the expression thymidine phosphorylase (TP), and also with the nuclear accumulation of the oncoprotein p53, but neither p53 nor TP was associated with VEGF expression by cancer cells or VEGF/receptor complex aMVD. In 35% of cancer cases examined, more than 20% of the microvessels assessed with anti-CD31 also expressed the VEGF/KDR complex. The vasculature of the normal head and neck mucosa did not express the VEGF/KDR complex. There was no association between VEGF expression or VEGF/receptor complex aMVD and response to chemo-radiotherapy or patient's survival. It is concluded that activation of the angiogenic pathway VEGF/flk-1(KDR) is tumor specific in a subgroup of locally advanced squamous cell carcinomas of the head and neck. Selective destruction of this type of vasculature, using immunoconjugates directed against the VEGF/receptor complex, may prove therapeutically useful for patients with a high tumoral VEGF/flk-1(KDR) activated microvessel fraction.

Adult↗

PubMed2000

Thymidine phosphorylase expression in normal and hyperplastic endometrium.

AIMS: To investigate the expression of thymidine phosphorylase (TP), a known angiogenic factor for endothelial cells, in normally cycling endometrium and various forms of endometrial hyperplasia. METHODS: TP expression was assessed with the P-GF.44C monoclonal antibody, using the alkaline phosphatase anti-alkaline phosphatase method. Ninety two normal and hyperplastic endometria were studied. RESULTS: In normal proliferative endometrium, TP is found exclusively in the basal layer and the inner third of the functionalis; expression is cytoplasmic in glandular epithelium and nuclear in stromal cells. It is invariably patchy. This immunohistochemical picture remains almost unaltered during the early and mid secretory phase of the normal menstrual cycle but, most impressively, TP is expressed uniformly in the epithelium of all endometrial glands towards the end of the cycle. At this stage, expression is mixed nuclear/cytoplasmic and there is very little stromal nuclear staining. In simple endometrial hyperplasia, the staining pattern for TP is identical to normal proliferative endometrium, with a distribution that is usually limited to a few rather weakly proliferating glands and to the adjacent periglandular stroma of the deep endometrium. The distribution is more extensive in complex and atypical endometrial hyperplasias, where a mixed nuclear/cytoplasmic pattern usually prevails over the pure cytoplasmic reaction. CONCLUSIONS: TP is expressed consistently in normal and hyperplastic endometrium, suggesting a role in physiological and pathological angiogenesis. In normal endometrium, TP has a definite pattern of distribution, which is dependent on the phase of the menstrual cycle, whereas in all forms of endometrial hyperplasia the enzyme is randomly distributed and lacks an orderly pattern.

Adult↗

PubMed2000

Angiogenic interactions of vascular endothelial growth factor, of thymidine phosphorylase, and of p53 protein expression in locally advanced gastric cancer.

The assessment of the angiogenic profile of tumors may become an important tool as a guide for the inclusion of novel drugs and molecular therapies into the standard chemoradiotherapy policy. Several studies have shown the prognostic importance of microvessel density (MVD) and of angiogenic factor expression in operable gastric cancer. In the present study we investigated, with immunohistochemistry the MVD, the expression of vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) expression, as well as the nuclear expression of p53 protein, in a series of patients with locally advanced inoperable gastric cancer. A strong association of VEGF with TP expression was noted (P = 0.005), and tumors coexpressing these factors had a statistically higher MVD (P = 0.0001). Nuclear p53 accumulation was also related to a high MVD (P = 0.004), and this was independent of VEGF or TP expression. Microvessel density showed a bell-shaped association with prognosis; cases with an intermediate MVD exhibit a favorable outcome (P < 0.05). A trend of nuclear TP expression to define a group of patients with poorer prognosis was noted (P = 0.06), while none of the remaining variables showed any significant association. The immunostaining results allowed the grouping of the angiogenic profile in four major categories: 1) highly vascularized tumors with VEGF and/or TP expression (about 36% of cases); 2) highly angiogenic tumors with p53 nuclear accumulation and low VEGF/TP expression (7% of cases); 3) poorly vascularized tumor with low VEGF/TP and negative nuclear p53 staining (32% of cases); 4) poorly vascularized tumors with TP expression (7% of cases). Specific therapies targeting hypoxia, VEGF, or TP expression as well as p53 gene therapy have entered clinical experimentation or are already available for clinical use. Using the suggested markers more than 80% of locally advanced gastric carcinomas can be grouped in different categories according to their angiogenic profile. Such a categorization may be useful for phase III trials on novel therapies targeting the major angiogenesis-related features studied here.

Adenocarcinoma↗

PubMed2000

Angiogenesis, thymidine phosphorylase, and resistance of squamous cell head and neck cancer to cytotoxic and radiation therapy.

Thymidine phosphorylase (TP), an enzyme involved in the thymidine synthesis and degradation, has been shown to promote tumor angiogenesis. Both TP expression and tumor vascularization are putative postoperative prognostic markers of cancer. Because of its bifunctional role, TP may have interactions with cytotoxic drugs or radiation via pathways requiring thymidine or prodrug activation. The microvessel score and TP expression were examined immunohistochemically on paraffin-embedded bioptical material from 94 locally advanced squamous cell head and neck carcinomas. All patients were treated with conventionally fractionated radiotherapy combined with induction (platinum- and 5-fluorouracil-based) or concurrent platinum chemotherapy. The follow-up of patients ranged from 6 to 108 months (median, 48 months). Nuclear TP expression was significantly associated with increased microvessel score (P < 0.0001, r = 0.45). A low percentage of cancer cells with nuclear TP expression in pretreatment biopsies was associated with a high rate of CR after combined chemoradiotherapy (P = 0.006) and induction chemotherapy (0.01). A better local relapse-free and overall survival was also observed in these patients (P = 0.001 and P = 0.0005, respectively). Biospies on the day after the delivery of 20 Gy of conventionally fractionated radiotherapy showed residual cancer cell nests, frequently of high vascularization and of intense nuclear TP reactivity. It is concluded that thymidine phosphorylase is associated with angiogenesis, with resistance to radiotherapy and cytotoxic therapy, and with poorer survival in squamous cell head and neck cancer. A strong rationale is provided for subsequent clinical trials of concurrent radiotherapy and chemotherapy with antiangiogenic agents or with specific TP inhibitors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Coexpression of MUC1 glycoprotein with multiple angiogenic factors in non-small cell lung cancer suggests coactivation of angiogenic and migration pathways.

We investigated the expression of MUC1 protein and its relationship to the microvessel density and the expression of thymidine phosphorylase, vascular endothelial growth factor (VEGF), VEGF-receptor KDR, basic fibroblast growth factor (bFGF), and bFGF-receptor (FGFR-2) in non-small cell lung cancer. Although MUC1 expression was found equally in poorly and highly vascularized tumors, a significant coexpression with multiple angiogenic factors and their receptors was noted (P = 0.0002, 0.03, 0.19, 0.10, and 0.01 for thymidine phosphorylase, VEGF, KDR, bFGF, and FGFR-2, respectively). In multiple regression analysis, both angiogenesis and MUC1 expression were independent prognostic variables. The present study suggests the existence of an early genetic event leading to the activation of both migration and angiogenesis pathways in non-small cell lung cancer.

Adult↗

PubMed2000

Invasive adenocarcinoma of mixed endocervical and clear cell type, associated with invasive squamous cell carcinoma of the cervix uteri. A case report.

A case of invasive adenocarcinoma (predominantly of endocervical type but also with clear cell elements blended in part of the growth) associated with squamous cell carcinoma of the uterine cervix is reported in a young woman aged 18 years. Malignant squamous and atypical glandular cells were detected in Papanicolaou (Pap) smears, which raised the question of a mixed tumor. A diagnosis of cervical cancer was justified by means of a punch biopsy and the patient was treated by modified radical hysterectomy. Histologic and immunohistochemical examination of the hysterectomy specimen revealed two distinct types of an invasive malignant tumor, i.e., of glandular and squamous cell origin, closely related but not integrated. Interestingly, the glandular component comprised both endocervical and clear cell elements. Careful consideration of squamous or glandular atypia in cytological smears may lead to a more precise diagnosis, especially in young women.

Adenocarcinoma↗

PubMed1999

Assessment of vascular maturation in non-small cell lung cancer using a novel basement membrane component, LH39: correlation with p53 and angiogenic factor expression.

Angiogenesis, the formation of new vessels, has been demonstrated to be a potent and independent indicator of prognosis in non-small cell lung cancer patients. The extent of differentiation of the tumor vessels may affect access of peripheral white cells and egress or invasion of tumor cells. This has not been assessed in relation to tumor microvessel density or other variables and may be a marker of vascular remodeling. LH39 is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly formed vessels. We examined the ratio of mature:immature vessels in 81 non-small cell lung carcinomas and correlated the vascular maturation index (VMI) to different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and to CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the percentage fraction of mature vessels (LH39 positive)/total number of vessels (CD31 positive). The median VMI in lung carcinomas was 46% (range, 15-90%). There was a significant inverse correlation between high VMI and low thymidine phosphorylase expression (P = 0.0001), high VMI and nuclear p53 negativity (P = 0.01), high VMI and low angiogenesis (P = 0.0001), as well as between high VMI and absence of nodal involvement (P = 0.01). Low angiogenesis and high VMI were associated with a significantly better outcome (P = 0.0001 and P = 0.02, respectively). These findings show that there is a wide variation in the differentiation of tumor vasculature in lung carcinomas, and VMI gives new information on the degree of active tumor vascular remodeling independently from microvessel quantitation.

Adenocarcinoma↗

PubMed1999

Chemopreventive activity of very low dose dietary tannic acid administration in hepatoma bearing C3H male mice.

Tannins are plant polyphenols comprising a heterogeneous group of compounds. Tannic acid is a common tannin found in tea, coffee, immature fruits, etc. and it has also been used as a food additive. An increasing body of experimental evidence supports the hypothesis that tannins exert anticarcinogenic activity in chemically induced cancers in animal models. In the present study, tannic acid was administered in very low doses in the drinking water of C3H male mice divided into three groups (75 mg/l, 150 mg/l and 300 mg/l). These animals carry a genetic defect and show a high incidence of spontaneous liver tumors (> 50%) at an age older than 12 months. The results showed a decrease in the overall incidence of hepatic neoplasms (adenomas plus carcinomas): 53.3% of animals in the control group developed hepatic neoplasms versus 33.3% in the group given a low dose of tannic acid, 26.6% in the group given a medium dose and 13.3% in the high dosage group. The difference was more pronounced in the animals with carcinomas: 4.44% of mice who received tannic acid developed carcinomas versus 33.3% of those in the control group. Tannic acid administration did not affect the PCNA labeling index of normal hepatocytes. It is concluded that tannic acid dietary intake in low doses can exert a strong dose-dependent chemoprotective activity against spontaneous hepatic neoplasm development in C3H male mice, most probably through antipromoting mechanisms.

Adenoma↗

PubMed1999

Thymidine phosphorylase expression in endometrial carcinomas.

Thymidine phosphorylase (TP) is a potent angiogenic molecule shown to induce endothelial cell migration and proliferation. We investigated the expression of TP in a series of 156 endometrial carcinomas, using immunohistochemical methods. Histopathological parameters of known prognostic significance and the molecular factors of p53, bcl-2 and angiogenesis were also assessed. Thymidine phosphorylase was expressed in cancer cells, stromal fibroblasts and myometrial cells. The pattern of TP staining was nuclear or mixed nuclear/cytoplasmic, and only exceptionally was purely cytoplasmic. An exclusively cytoplasmic staining was documented for the tumour-associated foamy macrophages. Cancer cell reactivity was rather limited; only 3.2% of endometrial carcinomas expressed TP in more than 50% of the neoplastic cell population and only 12% expressed the enzyme in more than 10% of the cancer cells. By contrast, TP reactivity was frequent in the fibroblasts of the tumour supporting stroma and the fibroblasts/myometrial cells at the invading tumour front, where approximately 1/3 of the cases expressed TP in more than 50% of the respective constituent cells. A high TP reactivity in the stromal fibroblasts was significantly associated with the presence of foamy macrophages and an intense lymphocytic response. A high TP reactivity at the invading tumour front was significantly associated with an intense lymphocytic response and the adverse prognostic parameters of high tumour grade, deep myometrial invasion, advanced stage of disease and the non-endometrioid carcinomas. There was no significant association of cancer cell TP reactivity with any of the parameters studied, including nuclear p53 accumulation, cytoplasmic/perinuclear bcl-2 expression, microvessel density (MVD) and prognosis. Similarly, no relationship was established between fibroblastic or fibroblastic/myometrial TP reactivity and MVD. It is concluded that TP is not a major angiogenic factor in endometrial carcinomas. However, a prominent TP activity at the invading tumour front, which is probably induced by cytokines of histiocytic and lymphocytic origin, may promote tumour invasion and progression.

Endometrial Neoplasms↗

PubMed1999

Intratumoral angiogenesis: a new prognostic indicator for stage I endometrial adenocarcinomas?

The prognostic significance of three recently emerged parameters, namely intratumoral angiogenesis and the antiapoptotic proteins bcl-2 and mutant p53, was investigated in a series of 124 patients with endometrial adenocarcinomas of the endometrioid cell type. All patients were treated with total abdominal hysterectomy and bilateral oophorectomy, without node dissection. When deep myometrial invasion or advanced stage of disease was confirmed, adjuvant radiotherapy was given. Intratumoral angiogenesis was assessed in tissue samples, after immunohistochemical staining, with the anti-CD31 monoclonal antibody. The mean microvessel density (MVD) was 23.2 +/- 14.1 (range 4-60; 95% CI 20-25.8). Microvessel density was high (> 30) in 30% of endometrial adenocarcinomas, medium (15-30) in 33% of the tumors, and low (< 15) in the remaining cases (37%). A strong cytoplasmic and/or perinuclear expression of bcl-2 in more than 10% of the neoplastic cells was considered as being positive, and noted in 35.5% of the endometrial neoplasms; it was more frequent in the less vascularized carcinomas (P = 0.03). Nuclear p53 accumulation in an equal percentage of neoplastic cells (> 10%) was less common (7.2%). In univariate analysis, early stage of disease, absence of lymphatic-vascular space invasion (LVI), and low intratumoral MVD were the parameters associated with an improved survival (P = 0.0001, P = 0.001, and P = 0.009, respectively). In multivariate analysis, however, the only independent variable noted was stage of disease (P < 0.0001). Within stage I endometrial adenocarcinomas, only intratumoral angiogenesis was associated with prognosis (univariate analysis): high MVD cases had a significantly worse prognosis compared to medium MVD (P = 0.02). Low MVD adenocarcinomas, on the other hand, were associated with an intermediate prognosis, indicating that other factors, such as hypoxia and related mechanisms, may also be important. It is suggested that intratumoral angiogenesis may prove useful in selecting a subgroup of cancer patients, among others with stage I endometrial disease, that would benefit from additional treatment.

Adenocarcinoma↗

PubMed1999

Oral administration of recombinant human granulocyte macrophage colony-stimulating factor in the management of radiotherapy-induced esophagitis.

Radiation-induced esophagitis often results in treatment interruption, which may severely affect the probability of control of the local disease in patients undergoing chest radiotherapy (RT). No effective regimen that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of oral mucosal healing using topical recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) has been reported, the mechanism of such an interaction remains obscure. Effective topical application of rhGM-CSF for the treatment of radiation-induced esophagitis has never been reported in the past. In pharmacological studies, we observed that glycerol exerts a remarkable stabilizing effect on rhGM-CSF immunoreactivity. After studying the kinetics of esophageal emptying with nuclear imaging, we proposed a rhGM-CSF regimen that could be applied for topical treatment of esophagitis during RT. The regimen was applied for 5 consecutive days in a cohort of 36 patients undergoing chest RT, immediately after the documentation of grade 3 esophagitis. RT was not interrupted. Mucosal biopsies were performed endoscopically and examined immunohistochemically. Regression of dysphagia to grade 0/1 was observed in 19 of 36 (52%) patients, whereas grade 2 dysphagia persisted in 12 of 36 (33%) patients. Progression of dysphagia was seen in 5 of 36 (14%) patients. Recurrence of severe esophagitis within 5-8 days after rhGM-CSF therapy was observed in 7 of 31 (22%) patients with initial response to rhGM-CSF. Four of these patients presented significant improvement of symptomatology after additional rhGM-CSF medication. In immunohistochemical studies, active intraepithelial neovascularization and thymidine phosphorylase and vascular endothelial growth factor overexpression were observed in the damaged epithelium, which was not accompanied by macrophage or neutrophil infiltration. We conclude that rhGM-CSF topical therapy (p.o. administration) exerts a significant therapeutic effect against RT-induced esophagitis. The rhGM-CSF mucosa healing effect is probably due to its direct angiogenic activity and/or to the potentiation of the activity of other angiogenic factors released by the damaged epithelium.

Administration, Oral↗

PubMed1998

Effects of melatonin on proliferation of cancer cell lines.

The pineal hormone melatonin has been reported to have in vitro antiproliferative effects on estrogen receptor-positive human breast cancer cell lines at concentrations near to plasma physiological concentrations (1 x 10(-11) to 1 x 10(-9) M). Its growth inhibitory actions have been thought to be linked to the estrogen-receptor system. We tested the cytotoxic effects of melatonin on MCF-7 and T47D human breast cancer cell lines by using the SRB (sulforhodamine-B), XTT-tetrazolium, and bromodeoxyuridine (BrdU) assays in 96-well microtiter plates. After a 3 or 4 day exposure, melatonin did not have any significant effect on breast cancer cell proliferation and survival in doses up to 1 x 10(-4) M. Doses higher than 1 mM exhibited a potent cytotoxic effect, which was not mediated by the estrogen-receptor or by protein tyrosine kinases and was not specific for breast cancer cell lines. Intracellular glutathione levels did not seem to play any role in the sensitivity of breast cancer cells to melatonin, since the addition of L-buthionine-[S,R]-sulfoximine, ethacrynic acid, or exogenous glutathione did not modify our results. We conclude that under our experimental conditions melatonin has no inhibitory effects on human breast cancer cells at low (physiological or supraphysiological) concentrations. The different experimental procedures that were utilized in the present study can partially explain the divergence between our results and the literature.

Breast Neoplasms↗

PubMed1997

Lymphomatoid papulosis type A: clinical, morphologic, and immunophenotypic study.

BACKGROUND: Lymphomatoid papulosis (LyP) is a cutaneous clonal or polyclonal Ki-1 + T-cell lymphoproliferative disorder, morphologically resembling Ki-1 + anaplastic large cell lymphomas (Ki-1 + ALCL) or Hodgkin's disease (HD). Lymphomatoid papulosis usually has a characteristic benign clinical course with remissions and relapses of the cutaneous eruptions. METHODS: The authors studied three patients with LyP. In each case the diagnosis was established based on the typical clinical history and presentation of the cutaneous lesions as well as the morphologic and immunophenotypic findings. RESULTS: In all three cases the skin biopsies showed a polymorphic, nonepidermotropic, dermal lymphocytic infiltrate, composed of small lymphocytes and fewer large, atypical cells. The large cells were positive for the activation markers CD30 (Ki-1) and CD45R (leukocyte common antigen), and were negative for the HD marker CD15 (Leu MI). CONCLUSIONS: In most cases, LyP can be distinguished from Ki-1 + ALCL and HD on the basis of clinical, morphologic, and/or immunophenotypic findings. We emphasize the importance of the recognition of LyP as a clinicopathologic entity and the awareness of dermatologists, oncologists, and surgical pathologists in differentiating LyP from other primary cutaneous Ki-1 + lymphoproliferative disorders (Ki-1 + ALCL and HD). The prognosis of cutaneous Ki-1 + ALCL and HD is usually different from LyP and requires a different therapeutic approach.

Adult↗

PubMed1997

Fetal magnetoencephalographic mapping in normal and pre-eclamptic pregnancies.

This study investigates the fetal brain activity in normal and pre-eclamptic pregnancies. Measurements were performed by means of a superconducting quantum interference device (SQUID) in an electrically shielded room of low magnetic noise. The study was prospective. Ten pregnant women with pre-eclampsia and 11 healthy gravidae were included. All were preterm at 28 to 37 weeks' gestation. Biomagnetic signals (waveforms), recorded from the fetal brains in the frequencies 2-7 Hz, were expressed in terms of magnetic power spectral amplitudes: these were low in almost all normal pregnancies, and high in most pregnancies complicated with pre-eclampsia. The pictorial representation of the results in the form of iso-spectral amplitude (ISO-SA) mapping showed two different patterns: (a) iso-contour lines 'organised' in dense concentration zones (pre-eclamptic pattern), (b) iso-contour lines at random distribution without dense concentration zones (normal pattern). Biomagnetic measurements of fetal brain activity is a promising screening procedure for assessing the cerebral function, especially at high risk pregnancies.

Journal Article↗

PubMed1997

The hemodynamics of the umbilical artery in normal and pre-eclamptic pregnancies. A new application of SQUID biomagnetometry.

This study was set to investigate the hemodynamics of the feto-placental circulation in normal and pre-ecclamptic pregnancies using the biomagnetometer SQUID. Thirteen women with pre-eclampsia and 26 healthy women were studied. All were "near term". Biomagnetic signals (waveforms) were recorded from the umbilical arteries. After statistical Fourier analysis, the findings were assigned arbitrarily in terms of spectral amplitudes as high (200-300 fT/ root of Hz), low (80-150 fT/ root of Hz) and borderline (151-199 fT/ root of Hz). In all cases the frequencies considered were distributed in the range 2-7 Hz. Interestingly, the umbilical artery waveforms and the corresponding spectral densities were of high amplitudes in most (88%) normal pregnancies of low amplitudes in most (84.6%) pregnancies complicated with pre-eclampsia. These findings were of statistical significance and were correlated with fetal heart rate (FHR) monitoring, pH and Apgar score at 1 and 5 minutes; high amplitude cases were related with normal FHR monitoring, pH > 7.25 and Apgar score > 7, while low amplitude recordings were connected with abnormal FHR patterns, pH < 7.25 and Apgar score < 7. It is suggested that biomagnetic measurements of the umbilical artery flow, which is an entirely new application of SQUID technology, is a promising procedure in assessing fetal health, especially in high risk pregnancies.

Adolescent↗

PubMed1996

The loss of lectin reactivity from human endometrium is a feature of malignant change.

Changes in the cell surface glycoproteins were investigated in endometrial adenocarcinomas using eight biotin-labelled lectins (Con A, LCA, WGA, e-PHA, l-PHA, SBA, PNA, LTA) which select for the major classes of N-linked and O-linked oligosaccharides. The tissues studied were 14 normal endometria, 20 cases of simple hyperplasia and 30 endometrial adenocarcinomas. Sections were cut at 5 microns from formalin fixed paraffin embedded blocks and were stained with an avidin-peroxidase method. All normal and hyperplastic endometria contained the full range of expected saccharides (positive staining for Con A, LCA, WGA, SBA, PNA, LTA, e-PHA and l-PHA). By contrast, over half of the endometrial adenocarcinomas exhibited a loss of galactosamine (56.7%) and over a third of them failed to reveal galactose (36.7%) and fucose (30.0%) (negative staining for SBA, PNA and LTA, respectively). Interestingly, following neuraminidase treatment, galactose was identified in all adenocarcinomas studied, but the expression of galactosamine and fucose was unaffected. There was a discrete linear staining at the level of the basement membranes in a proportion of endometrial glands treated with e-PHA, l-PHA and LCA; this was continuous in normal and hyperplastic endometria, while it was fragmentary in endometrial adenocarcinomas. The loss of galactosamine reactivity from endometrial adenocarcinomas was significantly correlated with high grade differentiation, and also with the more frequent occurrence of a poor oestrogen (ER) and progesterone (PR) receptor status and with an unfavourable 5-year survival. No relationship was found between fucose reactivity and tumour differentiation, stage of disease, hormone receptor status or prognosis. It is concluded that galactosamine loss, together with reduced fucose expression, is a common feature of endometrial malignancy, and that galactosamine deficient tumours may reflect a more aggressive biological behaviour.

Adenocarcinoma↗

PubMed1993

The prognostic significance of AgNOR counts in lymph node deposits of breast carcinomas.

Low AgNOR counts in metastatic lymph node deposits confer a longer 5-year survival rate in patients with breast carcinoma compared with those having high AgNOR counts. This was demonstrated in a series of 30 axillary lymph nodes from an equal number of patients with malignant breast disease. The beneficial effect of the low AgNOR status was independent of tumour differentiation, tumour size and the patients' age using univariate analysis, but it was related to the number of lymph nodes with metastatic disease. It is thought that AgNOR counts in axillary lymph node metastases may be an additional prognostic variable in assessing breast tumour behaviour.

Age Factors↗

PubMed1992

Chlorpromazine-induced damage on nucleic acids: a combined cytogenetic and biochemical study.

Chlorpromazine is now emerging as an adjuvant chemotherapeutic agent for the treatment of neoplasia. This was further supported in the present study by the following lines of evidence: it was shown that chlorpromazine causes damage in a series of native nucleic acids, though at somewhat high concentrations. Furthermore, chlorpromazine and caffeine were shown to act synergistically to potentiate the cytogenetic effect of adriamycin on human lymphocytes in vitro and on Ehrlich ascites tumour (EAT) cells in vivo. It is suggested that chlorpromazine alone or in combination with caffeine may exert its cytotoxic effect on normal and neoplastic cells not only indirectly, i.e. by facilitating the intracellular retention of adriamycin, but also directly by intercalating into nucleic acids.

Animals↗