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Biomedical subjects

G Zografos

Publications and source records attributed to G Zografos.

At least 19 recordsLinked to original sources
PubMed2006

Cytolytic and cytotoxic activity of a human natural killer cell line genetically modified to specifically recognize HER-2/neu overexpressing tumor cells.

NK92 cells genetically engineered to recognize the HER-2/neu oncoprotein have been previously reported to lyse HER-2/neu positive tumor cell lines through direct cell to cell contact. In the present study we have transduced NK92 cells with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5) antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3 zeta chain. NK92 cells expressing this chimeric receptor (NK92.HER-2/neu/zeta) specifically recognized and lysed HER-2/neu overexpressing tumor cell lines both in vitro and in preclinical tumor models in vivo. More important we demonstrate that NK92.HER-2/neu/zeta cells constitutively secrete high levels of soluble scFv which mediate strong tumor cytostatic effects by directly binding on cell surface HER-2/neu. Our data uncover an additional mechanism through which NK92.HER-2/neu/zeta cells mediate antitumor effects and further support their use in cell based therapeutics for the treatment of HER-2/neu expressing cancers.

Animals↗
PubMed2005

The use of isobutylcyanoacrylate as a tissue adhesive in abdominal surgery.

BACKGROUND: The use of cyanoacrylate substances as tissue adhesives is of valuable aid in surgery, especially in cases of injuries of the intraabdominal organs, where the haemorrhage is very difficult to control. MATERIALS AND METHODS: We investigated the efficiency of isobutyl-2-cyanoacrylate as a tissue adhesive in the haemostasis and adhesion of different types of wounds in solid and hollow organs. Forty-six dogs underwent single-organ (26 dogs) and combined-organ (20 dogs) procedures; cuneiform excisions of the liver and the spleen, as well as incisions of the small intestine were carried out. The wound surfaces were coated with isobutyl-2-cyanoacrylate and approximated. RESULTS: The majority (91.3%) of the surgical operations were uncomplicated, in which a very good macroscopical and histological result was achieved. Histological examination of the surgical injuries, performed 4 months later, confirmed complete wound healing. CONCLUSION: Isobutyl-2-cyanoacrylate proved to be a very effective tissue adhesive for both solid and hollow organs, even for high risk surgical operations.

Animals↗
PubMed2005

Identification of germline BRCA1 and BRCA2 genetic alterations in Greek breast cancer moderate-risk and low-risk individuals--correlation with clinicopathological data.

The current study was designed to evaluate the prevalence of BRCA1 and BRCA2 germline mutations in Greek moderate- and low-risk individuals with respect to clinicopathological phenotype and clinical outcome of breast cancer. Ninety-four consecutive individuals were prospectively recruited from two University Breast Cancer Clinics (Hippokrateion Hospitan and Laikon Hospital) between 1989 and 1999 and were categorized as moderate-risk and low-risk individuals for carrying BRCA1/2 germline mutations. To identify the underlying mutations, protein-truncation test and single-strand conformation polymorphism methods were used, followed by direct sequencing. Three novel BRCA1 missense mutations, one novel BRCA1 intronic deletion, three novel (previously reported) BRCA2 truncating mutations, and one novel BRCA2 missense mutation were identified in the moderate-risk group of individuals studied. The BRCA1/2 missense mutations as well as the single intronic variant identified were designated as unclassified genetic variants. Two BRCA1 unclassified genetic variants (missense mutations) were detected in two of the three (66.7%) male breast cancer patients analyzed, while the third one was identified in a sporadic (low-risk) breast cancer patient. Clinicopathological characteristics of breast carcinomas originating from BRCA1/2 heterozygotes were consistent with those already reported and not different from those observed in BRCA1/2 mutation (-) breast cancer patients. Furthermore, BRCA1/2 mutation carriers presented an excellent 4.5-year overall survival (100%). Our results reveal the unique characteristics of BRCA1/2 mutation status, genotype-phenotype correlations, and prognosis, in moderate- and low-risk individuals of Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2 genes appears to be a heterogeneous syndrome in the Greek population.

Adult↗
PubMed2004

Human leukocyte antigens as genetic markers in Greek patients with sporadic pancreatic cancer.

PURPOSE: In this study we investigated the relationship between specific HLA antigens and sporadic pancreatic cancer in Greek population. METHODS: The allele frequencies of serologically and molecular defined class I and II HLA antigens were studied in 60 unrelated patients with pancreatic cancer histologically confirmed. The results obtained for HLA frequencies were compared with those of 105 healthy control subjects (control group). RESULTS: Increased frequencies of HLA-A30 (16.7 vs. 3.8%; P < 0.01; OR = 5.05), A31 (9.5 vs. 1.9%; P < 0.05; OR = 5.72), B18 (31.7 vs. 14.3%; P < 0.05; OR = 2.78) and Cw7 (53.3 vs. 21.9%; P < 0.01; OR = 4.07) were observed in patients with pancreatic cancer in comparison to the control subjects. CONCLUSIONS: This study demonstrates the association between specific HLA antigens and pancreatic cancer development in whites and suggests a genetic susceptibility factor for the disease.

Aged↗
PubMed2004

Leucovorin and fluorouracil vs levamisole and fluorouracil as adjuvant chemotherapy in rectal cancer.

The aim of this study was to evaluate the effectiveness of 6-month therapy with leucovorin (LV) + 5-fluorouracil (5-FU) vs 12 months of therapy with levamisole (LVZ) + 5-FU, as adjuvant chemotherapy in patients with completely resected Dukes' stage B2 or C rectal cancer. One hundred and fifty patients with surgically resected rectal carcinoma, were enrolled in the present study; Dukes' stage B2 (n=70) or C (n=80), were randomly assigned to chemotherapy with 5-FU + LV x 6 months or 5-FU + LVZ x 12 months. Patient characteristics were equally balanced between the examined groups. Adjuvant CT consisted of LV 20 mg/m(2) intravenously (i.v.) plus 5-FU 450 mg/m(2) i.v., on days 1-5 every 4 weeks for 6 cycles or 5-FU 450 mg/m(2) i.v. every week plus LVZ 50 mg t.i.d x 3 days for 1 year. All patients received radiotherapy with a three-field technique to a total dose of 45 Gy, over 5 weeks. After a median follow-up of 7.4 years there were no significant differences between the two treatment groups with respect to the recurrence rates (P=0.821). Moreover, there was no difference in disease-free survival for patients stage Dukes' B2 (log-rank p=0.73); median for LV group 90 (8-131) months, and for LVZ group 86.5 (3-129) months. No difference was noted in disease-free survival for patients stage Dukes' C (log-rank p=0.73); median for LV group 60 (17-128) months, and for LVZ group 64 (2-123) months. There was no difference in overall survival for patients stage Dukes' B2 (log-rank p=0.75); median for LV group 90 (22-131) months, and for LVZ group 86 (10-129) months. For stage Dukes' C (log-rank p=0.73); median for LV group 67 (17-128) months, and for LVZ group 64 (5-123) months. Toxicities were as follows in the 5-FU + LVZ vs 5-FU + LV group; myelosuppression (leucopenia grade 3, 12% vs 4%, p<0.04), diarrhea (grade 0, 60% vs 76%, p<0.02), and liver toxicity (increase of transaminases >3-fold, 12 patients vs 2, p<0.03), were more frequent in LVZ group. None of the patients stopped chemotherapy because of the toxicity, and there were no toxicity-related deaths. In conclusion, adjuvant chemotherapy in RC with LV + 5-FU for 6 months is equally effective and less toxic than LVZ + 5-FU for 12 months.

Adult↗
PubMed2003

Incidental finding of gallbladder carcinoma detected during or after laparoscopic cholecystectomy.

AIM: Carcinoma of the gallbladder is a rare neoplasm with a dismal prognosis. With the increase of cholecystectomies due to the wide acceptance of laparoscopic cholecystectomy, the incidental diagnosis of gallbladder carcinoma is more frequent. We report our experience with gallbladder cancer diagnosed during or after the performance of laparoscopic cholecystectomy. METHODS: We evaluated 11 patients with gallbladder cancer out of 5539 patients who underwent laparoscopic cholecystectomy. Patient clinical and demographic characteristics were reviewed. RESULTS: Intraoperatively in 297 patients there was the suspicion of adenocarcinoma and frozen sections were performed. In four of them the diagnosis of adenocarcinoma was confirmed. In two of them the procedure was converted to open with gallbladder liver bed resection and regional lymph node dissection while the other two were considered inoperable. Of the remaining 5242 patients, seven were diagnosed postoperatively at the pathologic examination. Of these, five patients refused to undergo a repeat operation. We did not observe port site metastasis in any of our patients. Survival was low and ranged from 3-14 months. CONCLUSION: Gallbladder cancer runs a short course, with a poor prognosis. The use of a meticulous laparoscopic technique seems to be important for the diagnosis and the avoidance of early complications of the disease.

Adenocarcinoma↗
PubMed2002

Common prognostic factors for stage III melanoma patients and for stage I and II melanoma patients with recurrence to their regional lymph nodes.

This study was undertaken in order to identify the prognostic factors for stage III malignant melanoma patients. In addition we compared the survival data of these patients with data from patients presenting with stage I and II disease who subsequently developed a regional nodal recurrence, in order to identify common prognostic factors and to compare the biological behaviour of the two groups. We retrospectively examined two groups of patients. The first consisted of 116 patients with stage III malignant melanoma and the second consisted of 57 patients with stage I and II malignant melanoma that were found to have regional lymph node metastases diagnosed at least 6 months after surgical treatment of their primary lesion. The age of the patients, the number of disease-involved lymph nodes, the site of the primary lesion and the presence or not of palpable lymph nodes proved to be significant prognostic factors of the first group. We also analysed the survival data of the second group and compared it with data from the stage III patients. The 5 year survival starting from the time after diagnosis of the primary lesion was 47.37% compared with 25.86% in stage III patients; however, this difference was not statistically significant. Patients who present with stage III malignant melanoma seem to have a more aggressive phenotype than stage I and II malignant melanoma patients who present with recurrent disease in their regional lymph nodes. Disease behaviour is dictated by the number of disease-involved lymph nodes, the site of the primary lesion and the type of surgical procedure performed (elective or therapeutic lymph node dissection).

Adolescent↗
PubMed2002

Etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) in 5-FU+LV pre-treated patients with advanced colorectal cancer.

In the present study, we evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV+5-FU. Etoposide was administered at 3 different dose levels (DLs), in 3 groups of 20 patients each (total: 60); DL-I: etoposide 80 mg/m2, DL-II: etoposide 120 mg/m2, and DL-III: etoposide 180 mg/m2, in 45 min i.v. infusion, and followed in all levels by LV 100 mg/m2 i.v. over 1 hour and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered weekly until disease progression or unacceptable toxicity. No patients at DL-I responded, while 2 patients at DL-II and 3 at DL-III had a partial response (PR). Stable disease (SD) rates were as follows; at DL-I: 2, DL-II: 8 and DL-III: 9. More patients in DL-I progressed (n = 19) compared to DL-II (n=10) and DL-II (n = 8) (p < 0.0007). Time to progression was for DL-I, -II, -III: 17, 15, and 14 weeks, respectively. Median survival was DL-I, -II, -III: 30, 30, and 32.5 weeks, respectively. Toxicity consisted mainly of neutropenia, diarrhea and mucositis at all DLs, and was significantly more severe in DL-III. No difference was noted in responses between DL-II and DL-III. The authors conclude that the combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC and should not be recommended for further evaluation.

Adenocarcinoma↗
PubMed2000

An adult patient with a mixed germ cell tumor of the spermatic cord.

Tumors of the spermatic cord are very rare, and approximately one half of all primary spermatic cord tumors are malignant. We report the presentation and treatment of an adult (36-year-old) patient with a mixed germ cell tumor that originated in the spermatic cord. No similar cases of mixed tumors of the spermatic cord in adults have been reported.

Adult↗
PubMed2000

Prognostic factors in malignant melanoma patients with solitary or multiple brain metastases. Is there a role for surgery?

BACKGROUND: The aim of this study is to evaluate the prognostic parameters and treatment modalities of malignant melanoma patients with brain metastases. METHODS EXPERIMENTAL DESIGN: a retrospective study with a mean follow-up of 46 months. SETTING: specialized Cancer Center. PATIENTS: the charts of 136 patients, treated in Roswell Park Cancer Institute, for melanoma brain metastases, were analyzed. INTERVENTIONS: all patients were treated surgically and in the majority adjuvant therapy was applied. MEASURES: survival and time of recurrence of patients and possible prognostic factors. RESULTS: PATIENTS who were treated surgically had a better one-year survival rate (28.3%), than patients who received radiotherapy and/or chemotherapy (6.67%) or patients who refused any kind of treatment (3.45%), (p=0.006). Prolonged survival after surgical treatment was found in patients with single metastatic lesions and in patients with multiple metastatic lesions. CONCLUSIONS: Melanoma patients with single metastatic lesions to the brain seem to do better after surgical treatment. The role of surgical intervention in patients with multiple brain metastases needs re-evaluation from a big multicenter, prospective trial.

Adult↗
PubMed1999

The effect of various types of splenectomy on the development of B-16 melanoma in mice.

Two hundred and sixty CB57BL/J6 mice were used in an experimental protocol designed to investigate the effects of four different varieties of splenectomy on the growth rate of subcutaneously implanted GB-16 melanoma. In addition, the mean and absolute survival of the mice, the histopathology of the tumour and the effects of the same procedures on the immunological status of the tumour-bearing animals as assessed by serum IgG levels and immunoelectrophoresis were determined. The effects of timing of splenectomy and the removal of the primary tumour after splenectomy on the above parameters were also annotated. The following were found: 1. Splenectomy performed 8 days after B-16 melanoma tumour implantation in mice i.e. in the early period of oncogenesis, lengthened the survival of the grafted experiments, delayed tumour growth, reduced the "activity" of the tumour and caused pseudoencapsulation of the tumour by fibrous tissue. It increased, but not by a statistically significant degree (p > 0.05), the circulating levels of the IgG immunoglobulin. 2. Splenectomy performed 28 days prior to grafting of the same tumour did not affect the circulating IgG levels nor did it prolong survival; however it reduced the rate of tumour growth and pseudoencapsulation of the tumour was observed. 3. Splenectomy at the early stages of oncogenesis in combination with surgical removal of the primary tumour increased absolute and mean survival, delayed the tumour growth rate, increased the time to relapse and reduced the "activity" of the pseudoencapsulated tumour.

Animals↗
PubMed1998

Systemic cytokine response to hepatic resections under total vascular exclusion.

OBJECTIVE: To investigate the systemic cytokine response to major liver surgery as the basis for assessing potential new treatments. DESIGN: Open prospective study. SETTING: University hospital, UK. SUBJECTS: Thirteen patients undergoing elective hepatic resections that involved total vascular exclusion of the liver. INTERVENTIONS: Blood samples were taken preoperatively, during the operation, and during the first four postoperative days. Concentrations of endotoxin, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNFalpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were measured. RESULTS: Endotoxin concentrations were raised in 3/13 patients before operation and in 6 patients during the postoperative period. TNFalpha concentrations were undetectable. IFN-gamma and IL-1 responses followed a low and inconclusive pattern. IL-6 was significantly increased from 6 hours after operation to the third postoperative day, peaking at 699 (+/-277) pg/ml at 24 hours (p < 0.01). The two patients who died had the highest postoperative concentrations of IL-6. CONCLUSIONS: There is a pronounced systemic response to hepatic resection under total vascular exclusion that is reflected by the increase in IL-6 concentration and correlates with the operative blood loss and postoperative outcome. This might be used as an indicator of the response to specific treatments in this type of surgery. Treatments that minimise the IL-6 response to major hepatic resection may be of value.

APACHE↗
PubMed1997

[Experiences with surgical therapy of hepatic echinococcosis].

Between January 1984 and December 1990, 56 patients with hydatid liver disease were treated surgically at our Department. Diagnosis was made by using clinical criteria, serology and imaging techniques. Most frequent clinical symptom was abdominal pain or local discomfort (38 patients, 68%). Plain X-ray of the abdomen was helpful in 20 patients (36%), liver ultrasound in 53 (93%) and computerised tumorgraphy in 56 patients, (100%). The immunoelectrophoresis test of "arc 5" was sensitive in 51 patients (91%). Thirty patients (53%) underwent partial resection and omentoplasty, 17 patients (30%) underwent external drainage, two cystic resection (3%), one left lateral lobectomy (2%) and six (11%) underwent omentoplasty and T-tube insertion. Fatal complications did not occur. Four patients developed hepatic abscess (7%), three wound infection (5%), one bowel obstruction (2%) and in five instances (8%) drainage was maintained for more than three months. Of the 49 patients available for follow-up (87%), three (6%) developed recurrent disease.

Adult↗
PubMed1994

Chromosome allele loss in colorectal liver metastases and its association with clinical features.

Molecular genetic changes are better characterized in colorectal carcinoma than in other common adult tumours. Consistent allele losses, or loss of heterozygosity (LOH), on chromosomes 5q, 17p and 18q have been well established. These changes are associated with the prognosis of the disease. Little is known of such changes in liver metastases of colorectal origin. The extent of allelic loss and its association with clinical features were investigated in 19 patients with colorectal liver metastases by using 24 probes to detect restriction fragment length polymorphism. A high frequency of LOH on chromosomes 5q, 17p and 18q was found in these secondary tumours. No consistent loss has so far been shown in any other chromosome. The frequency of allele loss correlated significantly with prognostic features such as the number and size of liver secondaries (P < 0.005), metastasis to the lymph nodes (P < 0.01) and curative or palliative operation (P < 0.02).

Alleles↗
PubMed1994

Liver resection with total vascular exclusion for malignant tumours.

The records of 47 patients with no cirrhosis who underwent 56 liver resections under total vascular exclusion (TVE) for malignant tumours, both primary and secondary, were reviewed to study the effects of TVE. The mean (s.e.m.) blood loss was 1651(233) (median 1200 (range 200-8500)) ml and the mean(s.e.m.) intraoperative blood transfusion 930(100) (median 700 (range 0-2800)) ml. In 18 liver resections (32 per cent) no blood transfusion was administered. The mean(s.e.m.) postoperative hospital stay was 19.7(14.2) days. The 30-day operative mortality rate was nil but the hospital mortality rate was 4 per cent. Postoperative prothrombin time was influenced by the amount of liver resected and the duration of TVE but not by the amount of blood transfused. Postoperative serum levels of aspartate aminotransferase and bilirubin were not influenced by either the amount of liver resected or the duration of TVE.

Adult↗