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S Coca

Publications and source records attributed to S Coca.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of the antitumor activity of interleukin-12 in an experimental murine model of colorectal cancer induced by 1,2 dimethyl-hydrazine (DMH).

OBJECTIVE: Interleukin 12 (IL-12) is a cytokine that may enhance the proliferation and cytotoxic activity of T lymphocytes and natural killer (NK) cells. A relationship between extensive intratumoral infiltration of NK cells and longer survival rates in colorectal cancer (CRC) patients was previously noted. Preliminary evidence suggests that the combined administration of IL-12 and IL-2 may produce additive immunomodulatory activity. The purpose of this study was to determine whether the systemic administration of IL-12 (+/- IL-2) may induce an immune response against CRC as induced by 1,2-dimethylhydrazine (DMH). METHODS: Sixty-five 6-week-old Wistar rats were treated with weekly subcutaneous injections of DMH for 26 weeks at a dose of 20 mg/kg of body weight. Once tumoral induction was over, the animals were randomly allocated to one of three groups: I, control; II, intraperitoneal injections of IL-12; III, intraperitoneal injections of IL-12 combined with IL-2. At 30 weeks, all surviving animals were sacrificed. We studied the following parameters in each rat--number of tumors, size of tumors, and total tumoral volume. Tumor samples were studied using the monoclonal antibody CD 57 for the detection of NK cells. The extent of NK infiltration was classified as small, less than 50 NK cells/50 high-power field (HPF); moderate, 50 to 150 NK cells/50 HPF, and extensive, more than 150 NK cells/50 HPF. RESULTS: Thirty-five rats died before completion of the carcinogen exposure, and 30 rats were randomized (10 each group). In group II, 2 animals died during treatment. All rats in groups I and III developed tumors, while in group II two rats (25%) were tumor-free. Moreover, only one rat in group II developed multiple neoplasms, in contrast with group I and group III, where six rats (60%) and seven rats (70%), respectively, had more than one tumor. We found statistically significant differences in the mean number of tumors found in group II when compared to group I (p = 0.028) and group III (p = 0.019). Other parameters measured, such as biggest tumor size and total tumoral volume were found to be lower in group II, although no statistical differences were found between groups. Only 10% of rats in group I showed moderated/extensive NK cell infiltration, vs. 60% of rats in group II (p = 0.077) and 70% in group III (p = 0.02). CONCLUSION: The administration of DMH to rodents provides a reliable and consistent means of inducing CRC that may be suitable for the evaluation of anti-cancer therapies. Our findings suggest that IL-12 is effective against the development of experimental CRC. Its antineoplastic effect could be attributed to the stimulus of this cytokine on the intratumoral infiltration of NK cells.

1,2-Dimethylhydrazine↗
PubMed2003

Apoptosis is not correlated with the presence of CD57+ NK-cells in brain metastases.

BACKGROUND: Cell apoptosis in solid tumours has been related to immunological attack by NK-cells. The purpose of the present study is to verify in the tissue of brain metastases a possible relationship among the degree of NK-cell infiltration and the number of apoptotic tumour cells. METHODS: Twenty brain metastases whose tumour cells expressed CD95 (Fas/APO1) have been studied. NK-cells were identified by using the monoclonal antibody to CD57, and apoptotic tumour cells by means of the immunostain with the anti-ssDNA monoclonal antibody F7-26. The Spearman rank correlation test was used to study the relationship between the degree of CD57-NK-cell infiltration and the apoptosis labelling-index. FINDINGS: Positivity to F7-26 was present in all tumour samples, but the number of immunostained cells showed a wide variability, with a mean apoptosis labelling-index of 11.48%. All the studied tumours showed CD57 immunostained cells, with a number that ranged between 4 and 20 per microscopical field at 200x (mean+/-standard deviation: 8.4+/-3.7). Statistical studies showed that there was no correlation between the number of CD57 immunostained NK-cells and the apoptosis labelling-index (p>0.05). INTERPRETATION: These findings suggest that in brain metastases, apoptosis related to immune response is mainly mediated by activated tumour-infiltrating mononuclear cells other than CD57(+) NK-cells.

Adenocarcinoma↗
PubMed2003

Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer.

BACKGROUND: Survival at the intermediate stage of colorectal cancer (CRC) is less predictable than in the early and advanced stages. Several genetic markers possibly involved in growth and progression of CRC can be used for prognosis. AIMS: This study investigated the proportion of allelic loss (loss of heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient prognosis. PATIENTS AND METHODS: A total of 314 patients were investigated for LOH at the BRCA1 locus using polymerase chain reaction by means of three intragenic polymorphic microsatellite markers. Allelic losses were compared with clinicopathological characteristics of patients, recurrence rate, disease free survival (DFS), and overall survival. RESULTS: Twenty six patients were excluded because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%) were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was higher in patients with LOH (p=0.0003), and DFS was 73.3% (SEM 5.7) at five years in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss (p=0.0004). Retention of alleles at the BRCA1 locus was associated with a favourable DFS in stages I and II (p<0.05). The presence of LOH was also significantly associated with short overall survival (p=0.02). Multivariate analysis in the complete series showed that stage (p=0.006) and lymph node metastases (> or =4 nodes, p=0.0001; 1-3 nodes, p=0.038) were independent prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH was an independent prognostic factor in stages I and II (p=0.001). CONCLUSIONS: BRCA1 LOH is a molecular alteration present in CRC, with unfavourable repercussions for overall survival, that could be considered as an outstanding independent prognostic factor in stages I and II.

Aged↗
PubMed2002

Imbalance between apostain expression and proliferative index can predict survival in primary glioblastoma.

BACKGROUND: Cell proliferation and cell death are opposing processes in tumour growth, with tumour progression reflecting the balance between proliferating and apoptotic cells. The purpose of the present study is to verify the hypothesis that an imbalance between apoptosis and proliferation can predict survival in patients with primary glioblastoma. METHODS: After the immunohistochemical study of Apostain and MIB-1 expression, the index of apoptosis (AI), the index of proliferation (PI), and the ratio AI/PI was recorded for each tumour specimen, in a series of 32 primary glioblastomas. Studies of correlation between AI and PI, between AI and survival, between PI and survival, and between the ratio AI/PI and survival, were performed using the Spearman rank correlation test. Furthermore, a comparative study of survival was performed for subgroups of patients with ratio AI/PI greater or lesser than 1, using the log rank test. FINDINGS: In the present series, values of AI and PI showed a wide distribution, with a mean +/- SD of 8.16 +/- 7.2, and of 12.69 +/- 21.1, respectively. The values for the ratio AI/PI ranged between 0.01 and 6.03 (mean +/- SD: 1.44 +/- 1.60). Statistical study failed to obtain correlation between AI and PI. Survival of patients not correlated with AI neither with PI. The ratio between AI and PI did not correlate with survival either. Nevertheless, when survival for the subgroups of patients showing a ratio AI/PI greater or lesser than 1 was compared, a significant difference was found (p: 0.02). Survival ranged between 50 and 81 weeks (mean of 58.5 +/- 11.05 weeks) for the 12 cases showing a ratio AI/PI greater than 1, and it ranged between 8 and 85 weeks (mean: 38.20 +/- 25.37 weeks) for the 20 cases showing a ratio AI/PI lesser than 1. INTERPRETATION: Our present results suggest that a clear imbalance between cell proliferation and apoptosis can predict outcome in patients operated on for a primary glioblastoma.

Aged↗
PubMed2002

Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma.

OBJECTIVE: To study the prognostic significance of angiogenesis and enhancement on contrast-enhanced computerized tomography (CT) in oligodendrogliomas. MATERIAL AND METHODS: CD34 immunostaining was employed in samples of 26 low-grade oligodendrogliomas from patients treated by extensive resection and radiotherapy to determine the tumor angiogenesis index (TAI), calculated by measuring the immunostained endothelial surface area, in microm(2), per 1000 tumor cells. Preoperative CT scan was evaluated in each case, and the absence or presence of tumor enhancement after contrast administration was recorded. Survival was analyzed and statistically compared for subgroups of patients with lesions in which the TAI was less than or greater than 15, and for subgroups of patients having tumors showing presence or absence of enhancement on contrast-enhanced CT. RESULTS: Survival of patients with tumors showing a TAI of less than 15 was 100% and 71% at 5 and 10 years, respectively, vs a survival of 50% and 0% for patients showing a TAI of more than 15 (P < 0.05). The 14 patients whose tumors showed enhancement in preoperative contrast-enhanced CT had 5- and 10-year survival rates of 57% and 14%, respectively, vs 100% and 83% for the 12 patients whose tumors presented no enhancement (P < 0.05). Moreover, 79% of the tumors showing contrast enhancement had a TAI greater than 15, while 92% of those exhibiting no enhancement had a TAI of less than 15. CONCLUSION: These findings indicate a relationship between enhancement on preoperative CT scan and endothelial surface area in oligodendrogliomas, and suggest that this enhancement and the TAI may be considered angiogenesis-related factors with similar prognostic significance in terms of survival.

Antigens, CD34↗
PubMed2001

Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.

The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p < 0.05). Our present findings suggest the usefulness of VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma.

Adolescent↗
PubMed2000

Prognostic significance of clinical and angiogenesis-related factors in low-grade oligodendrogliomas.

BACKGROUND: Keeping in mind that oligodendrogliomas have unpredictable biological behavior, the aim of this study is to investigate the prognostic significance of VEGF expression and microvessel density in a homogeneous series of low-grade oligodendrogliomas. METHODS: For this study 36 patients with a low-grade oligodendroglioma treated by surgical resection and radiotherapy were selected. At the time of surgery, in all cases the Karnofsky Performance Scale (KPS) score was more than 70, and the study of the resected tumor disclosed a Ki-67/MIB-1 labeling index (MBI-1 LI) less than 1%. In this homogeneous series, immunohistochemical studies were performed using monoclonal antibodies against VEGF in order to study the expression of this cytokine, and against vascular endothelial CD-34 antigen, in order to identify microvessels. RESULTS: Our results show that in contrast to low-grade astrocytomas, low-grade oligodendrogliomas lacked immunoreactive VEGF. Oligodendrogliomas with low vascular density (less than 20 microvessels per microscopical field, at 200 x) or high vascular density (more than 100 microvessels per field, at 200 x) were identified, but this factor had no influence on the survival rate of patients. On the other hand, analysis of the present series showed that clinical factors, such as age or extent of surgical resection, were not significantly associated with survival. CONCLUSIONS: In contrast to low-grade astrocytomas, the angiogenesis score of low-grade oligodendrogliomas (counting the number of microvessels in tumor tissue) adds little information to help predict tumor behavior.

Antigens, CD34↗
PubMed2000

Prognostic significance of endothelial surface score and MIB-1 labeling index in glioblastoma.

The aim of this study is to investigate the usefulness of a vascular endothelial surface score (VESS) and MIB-1 labeling index (MIB-1 LI), in a defined series of glioblastomas, as biological markers with prognostic significance of survival. Tumor tissue and survival were studied in a series of 38 patients with glioblastoma, previously treated by surgical resection and radiotherapy. For each tumor, immunohistochemical and morphometric studies were performed in order to study MIB-1 LI, and VESS, expressed as the CD-34 immunostained endothelial surface per 1000 tumor cells. The survival for the entire patient population of the series was 48.1+/-14.1 weeks, and the mean VESS for the tumors of the series ranged from 16.7 to 107 microm2 per 1000 tumor cells (mean: 38.7+/-18.2). Factors such as age or MIB-1 LI were not significatively associated with survival, but the median survival for the 18 patients with a VESS less than 35 was 50.7+/-3.7 weeks, versus 45.9+/-2.8 weeks for the 20 patients showing a VESS higher than 36 (p < 0.05). Our present results suggest that tumor VESS, expressed as the CD-34 immunostained endothelial surface per each 1000 tumor cells, may have usefulness, as angiogenic-related factor influencing survival, in patients with glioblastoma.

Adult↗
PubMed2000

Cerebral angiofibroma: case report.

OBJECTIVE AND IMPORTANCE: Intracranial fibromatous tumors are very rare lesions, with few reported cases. CLINICAL PRESENTATION: We report the case of a 34-year-old male patient who experienced seizures resulting from a cystic lesion in the left occipital region, which remained unchanged for 11 years. After the seizures increased in number, magnetic resonance imaging revealed a large cyst with a tumor nodule. INTERVENTION: A left occipital craniotomy was performed, and the tumor was removed. Pathological studies, including immunohistochemical and ultrastructural analyses, indicated that this neoplasm was composed of fibrous and angiomatous components, and a diagnosis of cerebral angiofibroma was established. CONCLUSION: Cerebral and meningeal fibromas are rare neoplasms that differ from solitary fibrous tumors and fibrous meningiomas. When a number of prominent blood vessels are present in a cerebral or meningeal fibroma, a diagnosis of angiofibroma can be considered. It is possible that some nodular brain tumors that were previously described as meningioangiomatosis could be reclassified as cerebral or meningeal angiofibromas.

Adult↗
PubMed1999

Vascular permeability factor expression in cerebellar hemangioblastomas: correlation with tumor-associated cysts.

The presence of vascular endothelial growth/permeability factor (VEG/PF) has been studied in histological specimens from a series of 16 cerebellar hemangioblastomas. In this series, the tumors were classified as presenting a macroscopic solid pattern (4 cases), a mainly solid pattern with macroscopic cysts (4 cases) or a mainly cystic pattern (8 cases). Solid tumors showed a low degree (75% of cases) or moderate degree (25% of cases) of VEG/PF positivity. The mainly solid tumors containing macroscopic cysts showed a moderate degree (50% of cases) or high degree (50% of cases) of VEG/PF positivity. Nevertheless, mainly cystic hemangioblastomas showed a high degree (87.5% of cases) or moderate degree (12.5% of cases) of VEG/PF positivity. These findings suggest that the predominance of a cystic or solid macroscopic appearance of cerebellar hemangioblastomas may be influenced by the degree of VEG/PF expression within the tumor tissue.

Cerebellar Neoplasms↗
PubMed1999

Expression of vascular permeability factor in craniopharyngioma.

OBJECT: The expression of vascular endothelial growth/permeability factor (VEG/PF) has recently been correlated with the presence of tumor-associated cysts in some intracranial tumors. The purpose of this study was to evaluate a possible relationship between the presence of VEG/PF and the formation of cysts in craniopharyngiomas. METHODS: The expression of VEG/PF was studied in histological specimens from a series of 12 craniopharyngiomas. In this series, the tumors were classified as presenting a mainly solid pattern with small macroscopic cysts (four patients) or a mainly cystic pattern (eight patients). The mainly solid tumors containing small macroscopic cysts showed little or no VEG/PF positivity, which was mainly present in tumor cells surrounding cysts. Nevertheless, mainly cystic craniopharyngiomas showed a moderate or high degree of VEG/PF positivity in tumor cells. CONCLUSIONS: These findings indicate that the predominance of a cystic or solid macroscopic appearance of craniopharyngiomas may be influenced by the degree of VEG/PF expression within the tumor cells.

Adult↗
PubMed1999

Vascular endothelial growth/permeability factor in spinal cord injury.

OBJECT: Predicated on the hypothesis that this cytokine can contribute to the development of vascular hyperpermeability, leading to tissue edema after trauma, the purpose of this study was to determine the presence in tissue of vascular endothelial growth/permeability factor (VEG/PF) after experimental spinal cord injury. METHODS: The presence of VEG/PF was studied at 8 hours and 2, 8, and 14 days after a traumatic injury in adult Wistar rats. Studies were conducted in which a monoclonal antibody to the VEG/PF was used. Strong VEG/PF immunoreactivity was detected in the walls of pial and intramedullary vessels and in reactive astrocytes 8 hours posttrauma and was unchanged on Days 2 and 8. By Day 14, immunoreactivity decreased, and most of the arterioles from the pia and gray matter showed no mural VEG/PF. CONCLUSIONS: The authors' present findings suggest a role for this cytokine in the development of tissue edema after spinal cord trauma and point to the possible usefulness of a therapeutic approach to spinal cord injury based on blocking the cell expression of VEG/PF or its physiological effects.

Animals↗
PubMed1998

Expression of vascular endothelial growth factor in cerebellar hemangioblastomas does not correlate with tumor angiogenesis.

The relation between angiogenesis and tissue expression of vascular endothelial growth factor (VEGF) was studied in a series of 14 capillary cerebellar hemangioblastomas. In the present series, the number of intratumoral microvessels, identified by the endothelial marker CD34, does not correlate with the degree of VEGF expression. This finding suggests that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms.

Antigens, CD34↗
PubMed1998

Cyclosporine A induces apoptosis in murine tubular epithelial cells: role of caspases.

BACKGROUND: The pathogenesis of cyclosporine A (CsA) nephrotoxicity has not been completely elucidated. METHODS: The ability of CsA to induce apoptosis in cultured murine tubular epithelial cells and its regulation by the cell microenvironment and inhibitors of caspases were studied. RESULTS: This study found that CsA induces apoptotic death in murine proximal tubular epithelial MCT cells in a dose- (0.1 to 15 micrograms/ml) and time-dependent (24 to 72 hr) manner. Death caused by CsA is additive to apoptosis induced by deprivation of the survival factors present in serum. Primary cultures of murine tubular epithelial cells are also sensitive to CsA-induced apoptosis. Peptide inhibitors of caspases such as zVAD-fmk (which inhibits caspases 8 and 9) and DEVD-CHO (which inhibits caspase 3 and related caspases) prevented CsA-induced apoptosis in MCT cells, although zVAD-fmk was effective at lower concentrations. CONCLUSION: These data suggest that tubular cell apoptosis mediated by caspases may play a role in CsA nephrotoxicity and that the microenvironment modulates resistance to CsA lethality as low local levels of survival factors may potentiate nephrotoxicity. Caspases my be new therapeutic targets in the management of nephrotoxic injury.

Amino Acid Chloromethyl Ketones↗
PubMed1997

The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma.

BACKGROUND: Natural killer (NK) cells have a spontaneous cytotoxic capacity-against tumor cells. These cells represent a small proportion of human colon carcinoma-infiltrating lymphocytes. Their prognostic significance in these tumors has yet to be determined. METHODS: One hundred and fifty-seven patients who each had a colectomy for large bowel adenocarcinoma were studied. No patient received adjuvant therapy. Immunohistochemical stains were performed for NK cells using the monoclonal antibody CD57. The number of NK cells was counted using a MICRON image analyzer. The total area studied for each tumor was 1 cm2. In this area, 50 intratumoral fields of 0.173 mm2 were selected. The degree of NK infiltration was classified as little (< 50 NK cells), moderate (50-150 NK cells), and extensive (> 150 NK cells). The Kaplan-Meier method was used to obtain survival figures. Multivariate analyses were performed using the Cox regression model. RESULTS: At 5 years, patients with little and moderate NK infiltration showed significantly shorter survival rates (overall and disease free survival) than those with extensive infiltration (P < 0.01). Three significant factors affecting survival were selected in a stepwise fashion in increasing order as follows: TNM stage, NK infiltration, and lymphocytic infiltration. Patients with TNM Stage III disease and extensive NK infiltration showed significantly longer survival rates than those with little or moderate infiltration (P < 0.001). In these patients, multivariate analysis using the Cox regression model identified two significant variables: number of involved lymph nodes and NK cells infiltration. CONCLUSIONS: In patients with colorectal carcinoma, an extensive intratumoral infiltration of NK cells is associated with a favorable tumor outcome. Intratumoral infiltration of NK cells can be used as a variable with prognostic value, especially in patients with TNM Stage III disease.

Adenocarcinoma↗
PubMed1996

Gangliosides modulate the growth rate and cell phenotype of a murine primitive neuro-ectodermal tumour.

Intratumoural administration of gangliosides (GSD) into a murine primitive neuro-ectodermal tumour, growing in the epicranial subcutaneous tissue of syngenic rats, results in a decrease in the tumour growth rate and causes a more differentiated phenotype of tumour cell, with immunohistochemical expression of neuronal markers. These findings suggest that the potential usefulness of intralesional administration of GSD for the control of tumours of primitive neuro-epithelial character could be considered.

Animals↗