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Biomedical subjects

C Karakousis

Publications and source records attributed to C Karakousis.

At least 55 records · Page 3Linked to original sources

Phase II study--intra-arterial BCNU therapy for metastatic brain tumors.

Thirty-one patients with metastatic brain tumors (MBT) from lung cancer and ten patients with MBT from melanoma received BCNU, 100 mg/m2, every four weeks by intracarotid and/or vertebral artery infusion into each involved site. Twenty-five patients with lung cancer and all melanoma patients are currently evaluable. Twelve patients with lung cancer had complete and partial responses lasting from 1 to 14 months. Four of them with the histologic diagnosis of small cell carcinoma, one with large cell carcinoma and one with squamous cell carcinoma showed complete response. None of the patients with melanoma MBT experienced any response. All of the patients had periorbital erythralgia and/or occipital pain during the infusion. Four patients manifested mild focal seizures during the infusion or 6 to 24 hours after the treatment. Transient confusion with disorientation was observed in two patients 4 and 24 hours, respectively, after a BCNU infusion. Two patients developed reversible thrombocytopenia after the fifth course of the IA chemotherapy. Median survival of patients with MBT from lung carcinoma was 4 months, with two of them still alive at 10 and 14 months, respectively. Only one patients of the 25 with lung carcinoma died from MBT. Failure to control the primary disease resulted in the deaths of a vast majority of the patients.

Adenocarcinoma↗

Characterization of cells obtained by mechanical and enzymatic means from human melanoma, sarcoma, and lung tumors.

Characterization of cells comprising solid tumors will facilitate the rational design of cancer chemotherapy for individual patients. We have prepared cell suspensions from human melanoma, sarcoma, and lung tumors by thinly slicing the tissue with a microtome and scalpels (mechanical release), followed by treatment with a mixture of collagenase II and DNase I (enzymatic release). This method of disaggregation resulted in two cell suspensions for each tumor specimen, and we characterized these suspensions by assessing their dye exclusion capability, ribonucleoside triphosphate pools, cytological profile and clonogenicity in soft agar. The enzymatic method thus yields cells in addition to those obtainable by a mild mechanical procedure, and these cells are similar in cytological profile and clonogenicity in soft agar to those released mechanically. Furthermore, the enzymatically released population is superior to that released mechanically for purposes requiring large numbers of dye-excluding cells having intact ribonucleotide pools.

Cell Count↗

Cyclic nucleotide phosphodiesterases in normal and malignant human tissues.

Biopsy samples were obtained from tumor tissue and surrounding normal tissue from the same organs of the same patients in 25 patients. Adequate studies could be performed on all parameters in 18 tissue pairs: 12 malignant melanomas, 4 sarcomas, and 2 others. Significantly higher levels of cAMP low affinity phosphodiesterases were found in the tumors as compared to the controls. Similar differences were seen in the high affinity cAMP phosphodiesterases, but these were of borderline significance. High affinity cGMP phosphodiesterase levels did not differ significantly between normal and neoplastic tissue samples. Low affinity cGMP phosphodiesterases were not detectable in either tissues. These studies together with earlier experimental findings suggest possible auxiliary therapeutic trials with phosphodiesterase inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗

High incidence and characterization of glucocorticoid receptors in human malignant melanoma.

The glucocorticoid receptor was characterized in biopsy samples from patients with recurrent malignant melanoma. Glucocorticoid receptors were measured by the charcoal-adsorption technique. Tumor cytosol from approximately 86% (25/29) of the patients contained large quantities of receptors (20-324 fmol/mg protein). The dissociation constant of this cytoplasmic receptor was determined to be 2-22 nM. This binding component sedimented at 7.1S on sucrose gradients of low ionic strength and dissociated into lower molecular weight components that sedimented at 4.4S on sucrose gradients of high ionic strength. Receptor binding was specific for glucocorticoids. Although progestins competed well for the binding that is typical for glycocorticoid receptor as reported in the literature, other steroids, e.g., 17 beta-estradiol and 5 alpha-dihydrotestosterone, were only weak competitors. These results demonstrated that this neoplasm contains large quantities of glucocorticoid receptors that are similar in their physicochemical characteristics to those found in normal tissues. This finding in human melanoma biopsy specimens may be of therapeutic value in the management of patients with malignant melanoma.

Adult↗

Surgical management of metastases to the lung.

Our experience with 234 patients having resection of metastatic lesions of lung is reviewed. Most bilateral lung metastases were removed though a median sternotomy. Exploration of the contralateral lung with simultaneous removal of all lesions is possible through such an incision, and moreover, it appears to give less pain postoperatively. The over-all median survival time of the patients was 21.4 months, with a surgical mortality of 2.6 per cent. The therapeutic results were analyzed according to various factors. Incomplete resection and the presence of a positive hilar mediastinal node, or both, resulted in poor survival rate of the patients. Generally, the survival rates of the patients were found to be proportional to the disease-free interval and the tumor doubling time. Patients with a solitary lesion and those with two lesions removed had the best survival time. There was no difference in the survival rates of patients with unilateral and bilateral pulmonary multiple metastases. Treatment of metastases to the lung should be carefully planned in consultation with physicians who are acquainted with the natural history of the primary tumor, as lung resection is a part of the multimodal therapy of patients with solid tumor.

Adolescent↗

Treatment of adult neuroblastoma.

Twelve patients, all over 17 years of age, with adult neuroblastomas, an entity recently described, were seen at Roswell Park Memorial Institute for the period from 1950 to 1977. Four of these patients who were treated by multimodality therapy constitute the bulk of this report. One patient had a complete response and showed no evidence of disease 23 months after treatment with surgery and combination chemotherapy (CYVADIC); she also had maturation of established metastases. Another patient remained stable for 22 months after treatment with combination chemotherapy. These results indicate that chemotherapy may be effective treating adult neuroblastoma patients as complete remissions are achieved and survival times prolonged.

Adolescent↗

The role of hepatic artery ligation and dearterialization with infusion chemotherapy in advanced malignancies in the liver.

Because of limited benefits derived with the use of systemic chemotherapy, 15 patients with metastatic malignancy of the liver or hepatoma were treated by hepatic artery ligation (6) or dearterialization (9) and regional infusion chemotherapy. There were two postoperative deaths and three patients required surgical drainage of hepatic tumor liquefaction necrosis. The median survival was 14 months with two patients still living. The longest survivors were those patients with visceral leiomyosarcoma or carcinoid tumor. Five of the patients had failed to respond to previous chemotherapy, all showed a favorable response to this therapy. Rigid criteria for proper case selection have been developed which should reduce the operative mortality. Hepatic artery ligation is a therapeutic modality that can be of benefit to patients for whom no other satisfactory treatment is available.

Adult↗

Colony growth in soft agar of human melanoma, sarcoma, and lung carcinoma cells disaggregated by mechanical and enzymatic methods.

The effect of mechanical and enzymatic disaggregation on human malignant melanoma, soft-tissue sarcoma and lung carcinoma colony growth in soft agar was studied. The enzymatic disaggregation was advantageous in most cases of melanoma and sarcoma, giving a larger number of colonies and increasing the probability of achieving growth in soft agar. Enzymatically treated pulmonary carcinoma cell populations had lower clonogeneic potential, especially in the case of anaplastic carcinomas. Morphological studies showed that the cells growing in soft-agar colonies had the same characteristics as those of the original tumor. A linear relationship was obtained between the number of enzymatically and mechanically treated tumor cells plated and the number of colonies. Delayed plating decreased the number of colonies.

Agar↗

Implantable oxygen microelectrode suitable for medium-term investigations of post-surgical tissue hypoxia and changes in tumor tissue oxygenation produced by radiotherapy.

Teflon-covered platinum oxygen probes were used to monitor tissue oxygen levels in post-surgical cancer patients and those treated with radiotherapy. Progressive wound healing was usually accompanied by a decrease in tissue pO2. Radiotherapy produced a slight increase in pO2 while hyperthermia effected a significant increase in the oxygen level during 100% oxygen breathing.

Animals↗

Management of multiple lung metastases.

During the past seven years, 78 patients with multiple lung metastases under went lung resection. Most of the patients with bilateral lung metastases had lung resection through a median sternotomy rather than by bilateral thoracotomies. "Local excision" of the lung lesions was the most frequently used technique in order to preserve as much lung tissue as possible. Sixty-three of the 78 patients received adjuvant therapies following lung resection. Operative mortality was 3.8%. The over-all median survival was 18.3 months. Analysis of the data showed shorter tumor doubling time to be an indicator of poor prognosis, whereas other factors such as disease-free intervals and unilateral vs bilateral metastases did not affect the postoperative survival.

Adolescent↗

Problems in resection of chest wall sarcomas.

To illustrate the problems of reconstruction in major chest wall resection, five patients with a variety of soft tissue tumors of the chest wall, located at different sites, are presented. Patients, who underwent a lateral or posterolateral chest wall resection required removal of two to five ribs sequentially as well as the adjacent soft tissue. Those who underwent an anterior chest wall resection required resection of the manubrium or the body of sternum as well as of adjacent costal cartilages. To prevent instability of the chest, herniation, and to minimize flailing, the chest defect was bridged with the use of Marlex mesh. Whenever possible, the omentum was brought into the chest cavity to increase the vascularity of the reconstruction. Since, in most instances, the tumors involved the skin because of previous damage from radiation therapy, extensive skin coverage was planned well in advance of resection. Pedicle skin flaps or rotation flaps were used to cover the skin defect. Ventilatory support by volume respirator, was required for three to four days. In all patients, the chest wall was completeley stable after three to six weeks.

Adolescent↗

Lung resection for metastatic sarcoma.

Our experience with lung resection in fifty patients with metastatic sarcoma is presented. Seventeen patients underwent lung resection for solitary lung metastasis and thirty-three had multiple metastases. The overall estimated median survival of the patients was 22.2 months. Shorter tumor doubling time was found to indicate poor prognosis. The tumor-free interval, length of the waiting period, and the number of metastatic lesions removed did not influence the postoperative survival rate. Surgical therapy of solitary as well as multiple metastatic sarcoma of the lung appears to produce acceptable therapeutic results.

Adolescent↗

Human fibroblast interferon in human neoplasia: clinical and laboratory study.

Human fibroblast interferon (HFIF) produced on a large scale from normal diploid cell strains was highly purified and then evaluated as to its safety clinical investigation. The selective antiproliferative activity of HFIF was observed in vitro against certain human malignant cell lines and in vivo against human bladder tumors grown in nude mice. Direct injections of HFIF into metastatic melanoma lesions of two patients resulted in either the disappearance of malignant cells or the significant reduction in tumor volume.

Animals↗

Rectocolic reconstruction via a modified Kraske approach.

In carefully selected patients, the sacrococcygeal approach (Kraske's operation) with rectal colostomy can save a patient from abdominoperineal resection without loss of continence. This procedure is also useful in the management of rectal strictures that occasionally occur after leaks from the anastomosis of a low anterior resection of the rectosigmoid colon. Three illustrative cases are presented and discussed.

Adenocarcinoma↗

The posterior approach to rectal anastomoses.

The posterior approach to the rectum provides excellent exposure for benign lesions which are too high to be excised through the anus but too low to be excised transabdominally. As an adjunct to low anterior resection, it broadens the scope of the procedure without compromising the requirements of a proper operation for cancer.

Humans↗