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C Karakousis

Publications and source records attributed to C Karakousis.

At least 37 records · Page 2Linked to original sources

Recurrent breakpoints at 9q31 and 22q12.2 in extraskeletal myxoid chondrosarcoma.

A cytogenetic study of extraskeletal myxoid chondrosarcoma cells revealed a complex t(9;22;15)(q31;q12.2;q25) as a primary chromosome change. A reciprocal translocation involving identical breakpoints on chromosomes #9 and #22 in this tumor has been reported in the literature. We suggest that the breakpoints 9q31 and 22.q12.2 are associated with extraskeletal myxoid chondrosarcoma, a comparatively rare tumor of adulthood.

Aged↗

Chromosome changes in metastatic human melanoma.

Cytogenetic studies were performed on human malignant melanoma cells from eight metastatic lesions. Five tumors displayed near-triploid and three near-diploid chromosome numbers. Chromosomes #1, #6, #7, followed by #2 and #9, were found to be most frequently involved in structural aberrations. Aberrations involving chromosome #1, with deletions or translocations of 1p, involving region 1p12-1p22 in seven of eight breakpoints of the p arm were observed. Seven of nine breakpoints of 6q were located at region 6q15-6q21. Most of the breakpoints on chromosome #7 occurred near the centromeric region. All tumors had additional chromosome material involving 1q, chromosome #7 (7q in two tumors), and in five tumors an increased dose of chromosome #6 (6p in one tumor). The nonrandom breakpoints of these and other chromosomes involved diverse bands, including loci of oncogenes and fragile sites. The observation of nonrandom chromosomal changes in advanced malignant melanoma suggests that genes important in the progression of melanoma are located on chromosomes #1, #6, and #7.

Adult↗

Phase I clinical trial of ethyl 6-deoxy-3,5-di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809).

A phase I study of single i.v. doses of a new sugar containing nitrosourea 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809, EDMN) has been carried out in 47 patients with advanced solid tumors. Nine dose levels between 200 and 4500 mg/m2 were examined. Nausea and vomiting were seen in most patients but were controlled with antiemetics. Myelosuppression was minimal. The dose-limiting toxicity was hepatotoxicity, occurring early (peak at days 2-4) and resolving rapidly. No cumulative toxicity was seen with an every 6 weeks schedule. Other toxicities were abdominal pain, diarrhea, arm pain, restlessness, and headache. Pharmacokinetic studies in 20 patients using an HPLC assay and in 5 patients using [14C]EDMN showed a short half-life, rapid plasma clearance, rapid metabolism, and minimal excretion of unchanged drug. There was one partial response in a patient with colon carcinoma. The recommended dose for phase II studies in 3750 mg/m2 every 6 weeks.

Adult↗

Galactoside-binding lectin in human tissues.

Lactose-inhibitable lectin activity has been analyzed by hemagglutination assay in a variety of human tissues and cells obtained at surgery and autopsy. The lectin activity was detected in surgically removed melanoma, sarcoma, colon carcinoma, breast carcinoma, adjacent non-malignant tissues, non-malignant tissues obtained at autopsy and in cells isolated from malignant effusions. Although, on average, malignant tissue had a higher hemagglutinating titer than non-malignant tissue, similar tissues from different individuals varied widely in their apparent lectin content. The lectin was isolated from lung by affinity chromatography and was found to have a native molecular mass of 31,000 daltons and a subunit molecular mass of 14,000 daltons. Utilizing rabbit anti-lung lectin serum in an immunohistochemical assay, the lectin was found to be distributed throughout the cytoplasm of lung epithelial cells. Ouchterlony immunodiffusion analysis confirmed the presence of this lectin in a variety of tissues and in some body fluids. In vitro metabolic radiolabelling experiments showed that the presence of lectin in tissues was most likely due to endogenous synthesis rather than absorption from body fluids. Lectin isolated from several tissues was found to bind to human buffy coat cell receptors.

Electrophoresis, Polyacrylamide Gel↗

P-glycoprotein in human sarcoma: evidence for multidrug resistance.

Overexpression of an immunologically conserved, cell-surface glycoprotein (P-glycoprotein) is consistently associated with multidrug resistance in cell lines in vitro. A preliminary survey of specimens from 12 solid tumor types in our laboratories indicates significant overexpression of P-glycoprotein in some sarcomas. When tested by immunoblotting with monoclonal antibodies directed against P-glycoprotein; tumors from six of 25 sarcoma patients displayed elevated levels of P-glycoprotein. Three of the sarcoma patients exhibiting P-glycoprotein had not previously been exposed to chemotherapy, implying that overexpression of this marker and possible concomitant multidrug resistance may not depend only on selection during prior drug treatments. The P-glycoprotein overexpression in the sarcoma specimens is evidence for the presence of multidrug resistant cells in these tumors; thus, our data suggest that this mode of resistance may have clinical significance in sarcoma patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cytogenetic studies of adipose tissue tumors. I. A benign lipoma with reciprocal translocation t(3;12)(q28;q14).

Detailed clinical histories and cytogenetic investigations using short-term cultures are reported in three typical benign lipomas. Although a diploid (normal) karyotype was observed in two cases, a reciprocal chromosome translocation t(3;12)(q28;q14) was found in the third case, which was briefly reported previously. These data are discussed in light of a lipoma with similar karyotypic changes reported by Heim et al. and a similar translocation observed by us in malignant myxoid liposarcomas. The nonrandom involvement of segment 12q13-q14 in benign and malignant lipomatous tumors suggest a common basis for at least one of the possible multiple steps in the genesis of neoplastic processes.

Adult↗

Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas.

Detailed chromosome studies, briefly reported previously, from short-term cultures of tumor cells from myxoid liposarcomas are reported. A common reciprocal translocation, t(12;16)(q13;p11), was found in three cases and a complex t(1;12;16)(p11;q13;p11) in the fourth one. This nonrandom primary change, not described before in solid tumors, could characterize the myxoid form of liposarcoma. The involvement of a closely located breakpoint on chromosome #12 in a reciprocal t(3;12)(q28;q14) described in a lipoma in the previous article of this series, suggests a common basis in the biological process of proliferation of tumors sharing a common histogenesis.

Adult↗

Cytogenetic findings in a malignant melanoma and its derived cell line.

A cell line, MEL #26, was established from a metastatic solid tumor specimen obtained from a patient with malignant melanoma. Cytogenetic analyses were performed on both the fresh biopsy specimen (using short-term culture; 2 days) and an established cell line at three different passages. The chromosome number of the fresh biopsy specimen was in the near-triploid range and the chromosome number of the cell line was tetraploid. Three stable marker chromosomes involving #1, #6, and #7 were observed both in the original tumor and cell line. The marker chromosomes involving #1 and #7 were consistently present in all passages of this line, whereas, i(6p) was not present in every metaphase; a 15p+ marker completely disappeared after passage 20. Based on the results of the present study, we conclude that exclusive of one marker chromosome, the nonrandom chromosome changes seen in the original tumor were retained by the cell line and no particular additional clonal changes occurred during in vitro growth and establishment of this cell line. These considerations are of importance in the interpretation of results of various other studies that have been (or could be) performed with this cell line.

Cell Line↗

Surgical intervention of countless metastatic lung lesions: a case report.

A patient with countless metastatic bilateral lung lesions from sarcoma of an extremity was treated surgically. The patient is alive in good physical condition nearly 2 years following the surgery. Although there are residual pulmonary metastases, they appear to be stational. Surgical intervention of countless metastatic lung lesions may be indicated in selected cases.

Adolescent↗

Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

Autopsy↗

Serial cytogenetic analysis of a recurrent malignant melanoma.

A metastatic malignant melanoma in a 54-yr-old white female was examined cytogenetically on three different occasions. We found two different clones, one hypodiploid and another hypertriploid; however, both clones had the same markers [i.e., der(6),t(6;17), and der(17),t(1;17)]. Detailed analysis of the histopathology and clinical course suggests that these two different clones reflected different morphology and results of therapy.

Chromosome Aberrations↗

Plasminogen activators in human malignant melanoma.

Metastatic malignant melanomas from 16 patients, extracted with Triton X-100, were analyzed for plasminogen activator activity by azocaseinolysis . In 6 cases tumor explants were set up also in short-term organ culture, and the rate of plasminogen activator secretion into the culture medium was determined. Both the extractable activator content [8.66 +/- 7.8 "Committee on Thrombolytic Agents" (CTA) U/g tissue] and the activator secretion rates (0.90 +/- 1.6 CTA U/g/hr) were low in comparison with values for other human tumors. In addition to the activity, the type of plasminogen activator also was determined by immunoinhibition with goat antihuman urokinase antibody in the azocaseinolytic assay, as well as by sodium dodecyl sulfate (SDS) gel electrophoresis followed by zymography on fibrin-agar, in the presence and absence of antibody. On the average, 77% of the activator activity was of the urokinase type in the extracts, and 90% in the culture fluids. Immunoperoxidase reaction for the detection of urokinase showed this enzyme to be localized mainly in the cell membrane of the melanoma cells; stromal elements showed no specific staining. These results are of interest in view of the findings made recently by investigators in several laboratories that in all but one of the melanoma cell cultures derived from metastatic human tumors, only the vascular type ("tissue activator") was cell associated or was secreted into the culture medium. The possible reasons for this discrepancy are discussed.

Adolescent↗

Prostaglandin E2 production by human tumors. Defense mechanism against the host? A preliminary report.

Immunoreactive PGE2 was determined in 11 surgically removed malignant tumors. When compared to adjacent non-malignant tissues PGE2 content was significantly higher in the neoplastic tissues. These findings support the view that PG may play a role in cell proliferation and/or vascular supply to tumor tissues. The hypothesis was also discussed that PGE2 may represent a tumor against host defense since it can decrease spontaneous and antibody dependent cytotoxicity. PGE2 may also play a role in tumor induced osteoporosis and hypercalcemia. If this hypothesis is correct PGE2 synthesis inhibitors may be employed as auxiliary antitumor agents.

Dinoprostone↗

Management of cutaneous melanoma in the United States.

Melanoma is an especially important malignant disease for surgeons to know about, since it can be cured with surgical treatment if diagnosed at an early stage. In the American College of Surgeons Melanoma Survey of 4,545 melanoma patients diagnosed during 1980, the typical melanoma was relatively thin (less than 1.5 millimeters), not ulcerated (except in 9 per cent) and did not invade into the reticular dermis or beyond (level IV or V). The melanomas were most commonly located on the trunk in men and on the lower extremities in women. Eighty-eight per cent of the patients had no clinical evidence of metastases to regional nodes or to distant sites at the time of initial diagnosis. Only a small proportion (1 per cent) of patients in the survey were black and in most of these patients, their melanoma were located on the feet or hands. The treatment of melanoma was surgical in 92.5 per cent of the patients, with the majority of patients undergoing a wide excision of the melanoma as the initial form of treatment. Only one-fifth of the patients underwent elective regional node dissection for suspected micrometastases, and most of these patients had a tumor thickness exceeding 1.5 millimeters or a lesion invading to the reticular dermis (level III, IV or V). While the Breslow Microstaging Method is now recognized as the most important parameter that predicts the clinical course of the patient, this parameter was reported in only 45 per cent of the patients in the survey. The natural history of melanoma is changing, since the disease is increasing in frequency and becoming more curable. Surgical treatment should be tailored to the biologic aggressiveness of each individual patient's melanoma. This can be estimated by integrating such prognostic factors as the melanoma thickness, the presence or absence of ulceration, the level of invasion, the anatomic site and the gender of the patient.

Adult↗

The role of the tissue adhesive fibrin seal (FS) in esophageal anastomoses.

Following surgical removal of esophageal tumors, leakage and mediastinitis is a frequent and often fatal complication. A new method has been developed to seal suture lines in the esophagus with preparations containing fibrinogen, cold insoluble globulin, factor XIII, antiplasmin, platelet growth factor, thrombin, and calcium chloride. In experimental animals operated on by standard methods, esophageal leakage developed in 50% of the animals and death in 40%. By contrast, in treated animals, esophageal leak and death developed in only 20%. More adhesions were found in treated animals than in control animals.

Animals↗

High-dose cytoreductive therapy with autologous bone marrow transplantation in advanced malignancies.

Twenty-one patients with advanced malignancies received high-dose chemotherapy and/or radiotherapy followed by autologous bone marrow infusion. Eighteen patients (85.7%) had fever greater than or equal to 100 degrees F for a median of 6 days; 14 of these patients required broad-spectrum antibiotics for a median of 13 days. Nineteen patients (90.5%) had a granulocyte count less than 500/mm3 for a median of 11 days. Thrombocytopenia (platelet count less than 50,000/mm3) was observed in 18 patients (85.7%) for a median of 14 days. Mucositis and diarrhea were not common, occurring in six (28.6%) and seven (33.3%) patients, respectively. Of the 21 patients studied, 16 were evaluable for tumor response; there were four complete responses and four partial responses, and two patients who showed no change for variable times. Two patients have unmaintained remissions for greater than 2 years. Our response rate (complete plus partial) is 50%. Our study shows that high-dose cytoreductive therapy can be given with moderate toxicity when combined with autologous bone marrow infusion. Because responses in this group of patients are generally of short duration, we believe that patients with advanced malignancies who have had less exposure to therapy or who have a high likelihood of disease recurrence should be considered for high-dose cytoreductive therapy with autologous transplantation.

Adult↗

Nonrandom chromosome changes in malignant melanoma.

Chromosome aberrations were analyzed in 4 cases of malignant melanoma (MM) after disaggregation of the tumors with collagenase and short-term culture. In all cell cultures, the MM cells displayed a typical triangular spindle form. The chromosome number was near-diploid in one case and near-triploid in three cases. A total of 27 abnormal chromosomes were identified with the Giemsa banding technique. By far, the most common types of abnormalities were translocations, followed by deletions and isochromosomes. Chromosomes 1, 6, and 7 were found to be most frequently involved in structural aberrations. Markers originating from chromosomes 1 and 6 were found in all four cases, and abnormalities of chromosome 7 were found in three. Each marker chromosome was unique for a given case; no common markers for two or more cases were found. Based on the present results and an analysis of reports on the chromosomal constitution of MM cells in the literature, we suggest that abnormalities involving chromosomes 6 and 7 may be a characteristic feature of MM. Aberrations of chromosome 1, although common in MM, may be part of a general cytogenetic feature in human neoplasia.

Adult↗