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Biomedical subjects

W F Sindelar

Publications and source records attributed to W F Sindelar.

At least 91 records · Page 5Linked to original sources
PubMed1984

Detection of a pancreatic cancer-associated antigen (DU-PAN-2 antigen) in serum and ascites of patients with adenocarcinoma.

A competition radioimmunoassay was developed, utilizing a murine monoclonal antibody to human pancreatic adenocarcinoma cells. Immunoblotting of a standard antigen preparation from either serum or ascites fluid after electrophoresis in 1% agarose showed that the specific DU-PAN-2 activity resided in two major high molecular weight bands. DU-PAN-2 antigen levels were expressed as arbitrary units based on a standard partially purified antigen preparation. The inhibition curve with standard antigen was reproducible (SD less than 10%) and essentially linear from 25 to 200 units/ml. The mean DU-PAN-2 antigen concentration for the sera from 126 normal individuals was 81 units/ml. Sera from pediatric patients with malignancy had a mean of 127 units/ml, while nasopharyngeal, stage III melanoma, and ovarian carcinoma patients had means of 89, 92, and 119 units/ml, respectively. All values in normal subjects as well as the melanoma, nasopharyngeal, ovarian, and pediatric cancer patients were less than 400 units/ml. Intermediate antigen levels were detected in patients with alimentary tract malignancies. Eight of 20 gastric cancer and 8 of 76 colorectal carcinoma patients and 3 patients with benign or nonmalignant gastrointestinal tract disease had DU-PAN-2 values exceeding 400 units/ml. Ascites fluids from 6/6 and pancreatic juice from 2/2 pancreatic cancer patients had values greater than 750 units/ml. Serum from 68% of the 89 pancreatic cancer patients tested had DU-PAN-2 antigen levels greater than 400 units/ml. The mean serum value in this patient population was 4888 units/ml.

Adenocarcinoma↗
PubMed1984

Monoclonal antibodies against human pancreatic adenocarcinoma: distribution of DU-PAN-2 antigen on glandular epithelia and adenocarcinomas.

This report describes the distribution of antigen DU-PAN-2, defined by a monoclonal antibody raised against human pancreatic carcinoma cells, on a variety of tumors and nonneoplastic tissues. With the use of an immunoperoxidase technique, the antigen was detected on 16 of 16 pancreatic carcinomas, on 5 of 5 gallbladder or bile duct carcinomas, on the great majority of stomach adenocarcinomas, and, less commonly, on adenocarcinomas of other primary sites. Substantial intratumor heterogeneity of antigen expression was noted. DU-PAN-2 antigen was present on many types of normal glandular epithelial cells but often was more weakly expressed than on the corresponding tumors. The immunomorphology of staining, coupled with biochemical information known about the antigen, supports the notion that the DU-PAN-2 antigen is a mucin-like substance. Its relative restriction of expression on different types of glandular epithelium suggests that DU-PAN-2 antibody might be a useful reagent for helping to determine the site of origin of adenocarcinomas.

Adenocarcinoma↗
PubMed1984

Method of isolation-perfusion of the liver in the pig.

A method was developed in the pig for isolation-perfusion of the liver using a pump-oxygenator that infused blood through the portal vein after vascular isolation and collected the hepatic venous effluent in a closed recirculating system. Portal and vena caval blood flows were diverted around the liver by an intracaval conduit or by an external shunt. Leakage from the perfusion circuit into the systemic circulation was measured using radioactive albumin tracer. Ten pigs were perfused for 30 or 60 minutes at 37 C or 41 C. Nine animals survived treatment with transient elevations of hepatic enzymes but with no clinical or pathologic signs of permanent hepatic damage.

Animals↗
PubMed1984

Active immunization of hamsters against pancreatic carcinoma with lipid-treated cells or their shed antigens.

Increasing membrane lipid microviscosity of cells by treatment with cholesterol esters such as cholesterol hemisuccinate (CHS) enhances immunogenicity, probably by exposure of cryptic membrane antigens. Transplantable pancreatic carcinoma lines CBP and LSP-1 grown in inbred hamsters were tested for immunogenicity after CHS treatment. Tumor cells were incubated in CHS to rigidify cell membranes, and they were irradiated and injected i.p. into syngeneic hamsters. Incubation media after CHS treatment, considered to contain shed antigens due to hyperrigidification, were also used for immunization. Two identical immunizations using 10(7) cells or incubation media were performed 14 days apart. In control experiments, non-CHS-treated, irradiated cells were injected. Immunizations were performed using both syngeneic and allogeneic cells and supernatants for both the CBP and LSP-1 systems for specificity experiments. The degree of immunization in the treated hamsters was assessed by the response to a subsequent s.c. challenge with viable tumor cells given 7 days following the last immunization. For the CBP pancreatic cancer line, CHS treatment increased tumor immunogenicity significantly, as demonstrated by diminished tumor growth rate and by increased duration of survival after challenge. With the LSP-1 pancreatic tumor, immunization with CHS-treated cells showed no enhancement of immunogenicity. However, immunization with supernatant of CHS-treated cells resulted in a significant delay of tumor growth and increased survival, suggesting immunization by shed antigens in the CHS incubation medium. Use of CHS-treated cells or shed antigeneic material could be of potential value as a method of active immunotherapy.

Adenocarcinoma↗
PubMed1983

Staging laparotomy in early ovarian cancer.

Systematic restaging was performed prospectively in 100 patients referred to the Ovarian Cancer Study Group institutions with a diagnosis of "early" (stage Ia-IIb) ovarian cancer. Before referral, only 25% of patients had an initial surgical incision that was adequate to allow complete examination of the pelvis and abdominal cavity. In patients referred to member institutions, 31 (31%) of 100 were found to have a more advanced stage and 23 (77%) of 31 of these actually had stage III disease. Sixty-one percent of the patients had their advanced stage detected by procedures other than a second laparotomy-nine (29%) of 31 by peritoneoscopy, six (19%) of 31 by peritoneal washings, and six (19%) of 31 by lymphangiography. Sites of unsuspected disease are most likely to be pelvic peritoneum, ascites fluid, other pelvic tissue, para-aortic nodes, and the diaphragms. Based on these data, we conclude that the initial staging approaches traditionally used in clinical evaluation of patients with early ovarian cancer are often incomplete and inadequate.

Adolescent↗
PubMed1983

Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities.

Sixty-five patients with high-grade soft tissue sarcomas of the extremities were treated in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy with doxorubicin, cyclophosphamide, and high-dose methotrexate. Local therapy was administered using either amputation or wide local resection plus radiation therapy and the chemotherapy was begun in the immediate postoperative period. Actuarial analysis with median follow-up of 653 days revealed an advantage in continuous disease-free and overall survival in the patient group receiving chemotherapy (P = 0.0008 and P = 0.04, respectively, one-sided Mantel-Haenszel test). The continuous disease-free survival at three years is 92% in the chemotherapy group compared to 60% in the no chemotherapy group. Overall survival is 95% and 74% in these two patient groups. Fifty-eight percent of patients had limb-sparing surgery plus radiation therapy and 42% underwent amputation. In both treatment subgroups analyzed separately, chemotherapy resulted in an improvement in disease-free survival compared to randomized controls not receiving chemotherapy (P = 0.006 and P = 0.04 for groups receiving amputation and limb sparing, respectively). There were no local failures in the patients receiving chemotherapy and two local failures in the no chemotherapy group. The results of this trial confirm the historically controlled pilot trial performed in 26 patients between 1975 and 1977. A current update of the patients in the pilot trial, with a minimum four-year follow-up, reveals an improvement in disease-free and overall survival due to chemotherapy (P less than 0.002). Analysis of the previous pilot trial indicates that only few recurrences are seen beyond three years. Thus, it appears that adjuvant chemotherapy should be a part of the treatment adult patients with soft tissue sarcomas of the extremities.

Adult↗
PubMed1983

Demonstration of specific serologic reactivity in human osteosarcoma.

Cultured cell lines of osteosarcoma and normal skin fibroblasts were derived from tissues of five patients with localized osteosarcoma. Testing of pretreatment patient sera in an indirect immunofluorescence assay against both autologous normal fibroblasts and autologous osteosarcoma cells showed cytoplasmic staining. Quantitative absorption of patient sera with human fetal cells removed all reactivity against autologous fibroblasts, but fetal-absorbed sera showed cytoplasmic, membrane, and nuclear fluorescence when tested against autologous osteosarcoma. Testing the five patient sera against all five cell lines showed staining of allogeneic fibroblasts and osteosarcoma by nonabsorbed sera. Following fetal absorption, all reactivity against fibroblasts was removed, with the retention of specific staining of all osteosarcoma cell lines by all five patient sera. Additional testing of sera from normal patients, patients with soft tissue sarcomas, and patients with melanoma showed staining of allogeneic cultured fibroblasts and tumor cells derived from a patient with osteosarcoma. All staining against fibroblasts and tumor cells was eliminated by fetal absorption of the allogeneic sera. Results suggested that fetal neoantigens are expressed in cultured normal and malignant cell lines and that such fetal antigens are recognized by natural antibodies. Absorption of antifetal reactivity allowed demonstration of specific serum reactivity against osteosarcoma cells.

Antibodies, Neoplasm↗
PubMed1983

Demonstration of tissue-specific antigens shared by normal pancreas and pancreatic neoplasms.

Xenoantiserum raised against extracts of normal hamster pancreas, after absorption with normal tissues, reacted specifically with normal hamster and human pancreas by immunodiffusion. Absorbed antiserum also reacted with hamster and human pancreatic carcinoma but not with other neoplasms. Immunization of hamsters with normal pancreas extracts prevented growth of transplantable pancreatic carcinomas.

Adenocarcinoma↗
PubMed1983

Demonstration of type-R and type-C virus particles in hamster pancreatic adenocarcinomas.

Two transplantable solid tumors (CBP and PDP) and two continuous cultured cell lines (CBP-TC and PDP-TC) were established from nitrosamine-induced pancreatic ductal adenocarcinomas in inbred Syrian hamsters. Electron microscopic examination of both CBP and PDP solid tumors as well as CBP-TC cultured cells revealed the presence of type-R virus particles, which consisted of a 100 nm envelope containing a central 50 nm nucleoid with characteristic radiating 'spokes'. Type-R particles were abundant in cultured CBP-TC cells, moderately frequent in CBP solid tumors, and rare in PDP solid tumors; they were not present in PDP-TC cultured cells. The CBP and PDP solid tumors and cultured PDP-TC cells exhibited type-C viral particles, having a 150 nm envelope containing a 75 nm nucleoid. Mature, immature and budding forms of Type-C viruses were present and quite prominent in PDP tumors. Type-C particles were present but rare in CBP solid tumors and in PDP-TC cells. C-particles were not observed in cultured CBP-TC cells. Examination of normal hamster pancreas, liver, duodenum, muscle and connective tissue failed to reveal evidence of type-R or type-C virus particles. It is important to recognize the presence of virus particles in hamster pancreatic carcinoma lines, since viruses could potentially affect biochemical or immunological studies on the carcinomas through the production of viral proteins that could be mistaken for tumor-associated antigens.

Adenocarcinoma↗
PubMed1983

Effects of intraoperative electron irradiation in the dog on cell turnover in intact and surgically-anastomosed aorta and intestine.

Adult dogs were subjected to laparotomy and intraoperative electron irradiation after division and reanastomosis of aorta or after construction of a blind loop of small intestine having a transverse suture line and an end-to-side anastomosis. Dogs received intraoperative irradiation of both intact and anastomosed aorta or intestine in doses of 0, 2000, 3000, or 4500 rad. Animals were sacrificed at seven days or three months following treatment. At 24 hours prior to sacrifice, dogs received 5 mCi tritiated thymidine intravenously. Irradiated and non-irradiated segments of aorta and small intestine, including intact and anastomotic regions, were analyzed for tritiated thymidine incorporation and were subjected to autoradiography. Incorporation studies showed diminution in tritiated thymidine uptake by irradiated portions of aorta and small intestine, in both intact and anastomotic regions. Autoradiograms revealed that irradiated areas of intact or anastomotic aorta or intestine had diminished labeling of stromal cells, suggesting a lowered cell proliferative capacity of irradiated tissue compared to non-irradiated portions. Inflammatory cells showed similar labeling indices in irradiated and non-irradiated tissues, both intact and surgically-manipulated, suggesting that irradiation does not significantly affect a subsequent local inflammatory response. Radiation-induced decreases in tritiated thymidine incorporation in irradiated aorta and small intestine were generally more marked at seven days than at three months following irradiation, suggesting that radiation-induced depression of cell turnover rates decreases with time. The presence of tritiated thymidine uptake after irradiation demonstrates the ability of intact and surgically-manipulated aorta and intestine to recover from radiation-induced damage.

Animals↗
PubMed1983

Television system for verification and documentation of treatment fields during intraoperative radiation therapy.

Intraoperative radiation therapy (IORT) involves direct treatment of tumors or tumor beds with large single doses of radiation. The verification of the area to be treated before irradiation and the documentation of the treated area are critical for IORT, just as for other types of radiation therapy. A television system which allows the target area to be directly imaged immediately before irradiation has been developed. Verification and documentation of treatment fields has made the IORT television system indispensable.

Intraoperative Care↗
PubMed1983

Induction of delayed hypersensitivity reactions in cancer patients by cholesterol-hemisuccinate-treated autologous tumor cells.

Cholesterol-hemisuccinate (CHS) incorporated into tumor cells increases membrane lipid microviscosity and confers enhanced immunogenicity, which can be manifested by delayed hypersensitivity skin reactions. Skin testing was performed in 30 patients with various advanced malignant tumors. Patients were given intradermal injections of 10(6) autologous, irradiated, CHS-treated tumor cells. Control injections consisted of untreated irradiated tumor cells, CHS-treated autologous normal peripheral lymphocytes, or CHS-treated autologous normal tissues. For all patients tested, strongly positive skin reactions were observed when CHS-treated tumor cells were used. Untreated irradiated cells gave negative or very weakly positive reactions. In all cases, normal CHS-treated cells did not elicit any observable skin reactions. CHS-treated cells may have unmasked tumor-associated antigens to which patients may elicit immunologic responses.

Carcinoma↗
PubMed1983

Experimental and clinical studies with intraoperative radiotherapy.

Studies of normal tissue tolerance to intraoperative radiotherapy were done upon 65 dogs subjected to laparotomy and 11 million electron volt electron irradiation in doses ranging from zero to 5,000 rads. Results of studies indicated that intact aorta and vena cava tolerate up to 5,000 rads without loss of structural integrity. Ureteral fibrosis and stenosis develop at doses of 3,000 rads or more. Arterial anastomoses heal after doses of 4,500 rads, but fibrosis can lead to occlusion. Intestinal suture lines heal after doses of 4,500 rads. Bile duct fibrosis and stenosis develop at doses of 2,000 rads or more. Biliary-enteric anastomoses fail to heal at any dose level. A clinical trial of intraoperative radiotherapy combined with radical surgery was performed upon 20 patients with advanced malignant tumors which were considered unlikely to be cured by conventional therapies and which included carcinomas of the stomach, carcinomas of the pancreas, carcinomas involving the hilus of the liver, retroperitoneal sarcomas and osteosarcomas of the pelvis. All patients underwent resection of gross tumor, followed by intraoperative irradiation of the tumor bed and regional nodal basins. Some patients received additional postoperative external beam radiotherapy. Treatment mortality for combined operation and radiotherapy occurred in four of 20 patients. Postoperative complications occurred in four of the 16 surviving patients. Local tumor control was achieved in 11 of the 16 surviving patients, with an over-all median follow-up period of 18 months. The clinical trial suggested that intraoperative radiotherapy is a feasible adjunct to resection in locally advanced tumors, that the resulting mortality and morbidity is similar to that expected from operation alone and that local tumor control may be improved.

Abdominal Neoplasms↗
PubMed1982

Nitrosamine-induced pancreatic carcinogenesis in outbred and inbred Syrian hamsters.

Pancreatic carcinogenesis was investigated in outbred and in five strains of inbred Syrian golden hamsters utilizing the nitrosamines N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP). Thirty eight outbred hamsters were treated for an average of 15 weeks with weekly s.c. inoculations of BHP at doses of 250,000 or 1000 mg/kg. Pancreatic carcinomas developed in 19%. Eighty nine inbred hamsters of strains CB, LHC and PD4 were given BHP at 250 mg/kg weekly for an average of 25 weeks. Pancreatic carcinomas developed in 61%. Pancreatic inflammation, fibrosis, and ductal hyperplasia were prominent. Toxic changes in the liver, biliary hyperplasia, and pulmonary interstitial inflammation were also prominent features of BHP-treated hamsters, along with occasional carcinomas of the liver and respiratory tract. One hundred and sixteen inbred hamsters of strains CB, LHC, LSH, MHA, and PD4 were treated with BOP at a dose of 5 mg/kg weekly for 15 weeks. The incidence of pancreatic carcinoma was 51%. BHP-treated hamsters exhibited pancreatic fibrosis and ductal hyperplasia. Livers of BHP-treated animals showed biliary hyperplasia, and lungs exhibited chronic inflammation. Occasional carcinomas of the liver and lung developed. From 243 hamsters treated with nitroso carcinogens, eight pancreatic ductal adenocarcinoma lines were derived that can be transplanted and propagated in inbred hamsters.

Adenocarcinoma↗
PubMed1982

The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy.

Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m2), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomized to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p1 = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (71% and 78% at five years; p2 = 0.75) or overall survival rates (83% and 88% at five years; p2 = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p1 less than 0.0001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p1 = 0.0008) and overall survival (95% vs. 74%; p1 = 0.04). Thus limb-sparing surgery, radiation therapy, and adjuvant chemotherapy appear capable of successfully treating the great majority of adult patients with soft tissue sarcomas of the extremity.

Adolescent↗
PubMed1982

Tolerance of retroperitoneal structures to intraoperative radiation.

In conjunction with the clinical development of intraoperative radiotherapy, a study was undertaken in dogs to define the tolerance of normal anatomic structures in the retroperitoneum to radiation delivered during operation. Twenty adult dogs were subjected to laparotomy and intraoperative 11 MeV electron irradiation in single doses ranging from 0.to 5000 rad. Animals were followed regularly with clinical observation, blood count, serum chemistries, pyelography, and angiography. Animals were sacrificed and autopsied at regular intervals up to 12 months following treatment to assess radiation-induced complications or tissue damage. Irradiation field in all dogs consisted of a 4 X 15 cm rectangle extending inthe retroperitoneum from the level of the renal vessels to the bifurcation of aorta and vena cava. The field included aorta, vena cava, inferior portion of left kidney, and distal portion of left ureter. No complications or histologic changes occurred in any animal given doses of 2000 rad, with a follow-up in excess of 18 months. A dose of 3000 rad was well tolerated, except for left ureteral occlusion in one animal. Mild vascular fibrosis was present inthe aorta and vena cava, and significant ureteral fibrosis developed by six months after doses of 4000 or 5000 rad. All animals that received 5000 rad died of radiation-related complications, including ureteral obstruction and rectal perforation. It was concluded that major vessels tolerate intraoperative irradiation well up to and including 3000 rad and that no clinically significant vascular problems develop after 4000 and 5000 rad, although some fibrosis does occur. The ureter and kidney appear to be the most radiosensitive structures inthe retroperitoneum, showing progressive changes at 300 rad or greater and showing the potential for serious complications after doses of 4000 rad or more.

Animals↗
PubMed1982

Evidence for acute cellular changes in human hepatocytes during anesthesia with halogenated agents: an electron microscopic study.

Liver biopsy specimens of 24 patients who had elective laparotomies were studied by electron microscopy for evidence of anesthesia-related toxic changes. All patients were initially anesthetized with nitrous oxide, barbiturate, and narcotic until the laparotomy incision was completed and an initial preanesthesia liver biopsy specimen was taken. Patients were then give, in randomized fashion, maintenance inhalational anesthesia for the duration of the procedure with halothane, fluroxene, or enflurane. Control patients were continued on nitrous oxide, barbiturate, and narcotic. After approximately 60 minutes a second postanesthesia liver biopsy specimen was taken. For each patient, the preanethesia and postanesthesia liver biopsy specimens were compared, in blinded fashion, for evidence of morphologic changes resulting from anesthesia. Ultrastructural changes consistent with hepatic toxicity were present in more than 25% of the cells examined in the postanesthesia specimens in all of the seven patients given halothane, five of the six patients given fluroxene, and one of the five patients given enflurane. None of the six nitrous oxide-barbiturate-narcotic control patients showed toxic changes in postanesthesia specimens. The most prominent toxic change was dilatation of endoplasmic reticulum. Accumulation of intracellular inclusions occurred in some cells, and a small percentage of cells also showed lipid accumulation and mitochondrial swelling. Evidence suggested that exposure to halogenated anesthetics is related to acute toxic subcellular changes in hepatocytes.

Adolescent↗