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Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 109 records · Page 6Linked to original sources
PubMed1986

Characterization of a new monoclonal antibody to a cell surface antigen on colorectal cancer and fetal gut tissues.

Murine hybridoma were raised against the human colon carcinoma cell line CL-187. One clone was found to secrete a monoclonal antibody (ND-1) that recognizes a large external antigen (LEA) on human colon carcinoma cells. With indirect immunofluorescence on formaldehyde-fixed cells, more than 90% of the human colorectal carcinoma cell lines tested expressed LEA. Almost all of the 46 human noncolorectal and nonhuman cell lines tested did not express LEA, including cancer cell lines from other endodermally derived tissues. Staining of frozen sections from human colorectal tumors, noncolorectal tumors, normal adult, and normal fetal tissues showed expression of the antigen on colorectal cancer tissue, fetal colon, and fetal biliary epithelium. LEA can also be detected in the serum and ascites of colorectal cancer patients. Double indirect immunofluorescence with rabbit anti-carcinoembryonic antigen (CEA) antibody and ND-1 monoclonal antibody on a human colorectal carcinoma cell line showed that LEA is distinct from CEA. Physicochemical analysis of LEA showed that it has a large molecular weight, is resistant to extraction from the cell surface, and that sialic acid is an important component of the antigenic site. Because of the specificity for colorectal cancer tissue along with certain biochemical properties, LEA appears to be unique when compared with other tumor-associated antigens. Further research is needed to define the clinical usefulness of LEA in either the diagnosis or treatment of colorectal carcinoma.

Animals↗
PubMed1986

The effect of alloimmunization on recurrence in an experimental colon cancer model.

Primary bowel tumors were induced in Wistar/Furth (W/Fu) rats by 16 weekly injections of 1,2-dimethylhydrazine (DMH). After curative resection, 70% to 75% of control rats who receive no further treatment developed local or regional recurrence within 22 weeks. Rats immunized with three weekly subcutaneous inoculations of 1 X 10(6) irradiated (10,000 rad) Brown Norwegian (BN) X W/Fu F1 or Buffalo (Bu) tumor cells (both containing colon cancer tissue-type specific antigens [TSA] but differing from the W/Fu at Ag-B [histocompatibility] loci) developed recurrent tumor at a rate not significantly different from untreated or concurrent Ag-B antigen matched non-TSA treated controls. By 22 weeks after tumor resection, 63% of rats immunized with BN X W/Fu F1 colon adenocarcinoma and 52% of those immunized with Bu adenocarcinoma had recurred. Sixty-one percent and 44% were the respective recurrence rates for rats immunized with strain matched renal cell tissue. These data show nonspecific protection against tumor recurrence because of alloimmunization but clearly demonstrate the subordination of any beneficial colon cancer TSA immunotherapeutic effect by contained histocompatibility antigens. The problem of such nonspecific immune stimulation by alloantigen overriding an expected specific effect by TSA and possible alternative methods of immunization to prevent this phenomenon are discussed.

Animals↗
PubMed1986

Increased expression of the epidermal growth factor receptor on human colon carcinoma cells.

Epidermal growth factor (EGF) is a small polypeptide hormone that promotes the growth of cells in culture and elicits the differentiation of epithelial tissues in vivo. The effect of EGF is mediated by a transmembrane receptor that is expressed in increased amounts on some tumor cells. We have used a monoclonal antibody to the EGF receptor to detect increased expression of the receptor on human colon carcinoma cells. All eight of the moderately well-differentiated colon carcinoma cell lines tested and several frozen colon carcinoma tissue sections showed increased expression of the EGF receptor, while five poorly differentiated colon carcinoma cell lines and normal colon tissue sections did not. Increased expression of the EGF receptor on moderately well-differentiated colon carcinoma cells but not on poorly differentiated colon carcinoma cells was also demonstrated by western transfer and iodine 125-labeled EGF binding assays. Increased expression of the EGF receptor on moderately well-differentiated colon carcinoma cells seems to be a useful marker for the differentiation of human colon carcinoma cells. In addition, it might provide a site for adjuvant hormonal therapy or immunotherapy.

Antibodies, Monoclonal↗
PubMed1986

Inhibition of rat colon tumor isograft growth with dequalinium chloride.

In searching for a new approach to the systemic treatment of colorectal carcinoma, we have observed that certain lipophilic cationic compounds are accumulated and retained for a significantly longer period in the mitochondria of living carcinoma cells than in normal cells or sarcoma cells. We report the in vivo therapeutic effect of one of these compounds, dequalinium chloride, on the W163 rat colon carcinoma isograft, which grows rapidly in Wistar/Furth rats after primary tumor implantation, and which recurs rapidly after primary tumor resection. In the primary transplant model, tumors were implanted, and daily dequalinium chloride treatments were begun the following day in doses ranging from 1 to 10 mg/kg. In the recurrence model, isografts were implanted, allowed to grow for one week, and then all gross tumor was resected. Dequalinium chloride was administered in varying daily doses starting the day after resection. In both models, tumor was removed on day 11 after implantation or resection. At sublethal doses, dequalinium chloride significantly inhibited primary tumor growth to 60% that of controls and recurrent tumor growth to 50% that of controls. We propose that this unique biologic approach of targeting carcinoma mitochondria with lipophilic cationic compounds may provide a major new opportunity for treating colorectal carcinoma.

Animals↗
PubMed1986

Effects of polychlorinated biphenyls and lipemia on serum analytes.

Twelve serum analytes [triglycerides, cholesterol, total and conjugated bilirubin, high-density-lipoprotein cholesterol (HDL-C), alkaline phosphatase (AP), gammaglutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), beta-glucuronidase (beta-glu), alanine aminopeptidase (AAP), and 5'-nucleotidase (5'nuc)] were measured to investigate their correlation with exposure to polychlorinated biphenyls (PCBs) and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). The relationship between serum lipids, lipophilic toxicants, and the analytes was also evaluated. The beta-glu, 5'nuc, triglycerides, cholesterol, and total bilirubin correlated positively and significantly with log concentrations of serum total PCBs and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a metabolite of DDT. The more highly chlorinated PCBs (Aroclor 1260) had significant, positive correlations with several serum analytes, but the less chlorinated PCBs (Aroclor 1242) correlated significantly and negatively only with HDL-cholesterol. Triglyceride- and cholesterol-rich lipoproteins were added to serum to determine the effects of lipids on these assays. Several were spuriously elevated. AP and beta-glu were not affected by lipoprotein addition with the methods used in this study. AAP was increased significantly only at triglyceride concentrations exceeding 400 mg/dl. Lipoproteins may be elevated because of deranged lipid metabolism in response to PCBs, or PCBs may be elevated because elevated lipoproteins are present, as in familial triglyceridemia, a relatively common dyslipoproteinemia. Because this relationship is not well understood with respect to cause and effect, we propose the further use in epidemiological investigations of assay methods that are little affected by blood lipids yet are correlated with PCB concentrations. Congener-specific quantification of PCBs would help elucidate the effects of PCBs on assays used to monitor health effects.

5'-Nucleotidase↗
PubMed1986

Evaluation of potential health effects associated with serum polychlorinated biphenyl levels.

In late 1983, we conducted a cross-sectional epidemiologic study to evaluate persons at risk of exposure to three chemical waste sites by comparing clinical disease end points and clinical chemistry parameters with serum polychlorinated biphenyls (PCB) levels. A total of 106 individuals participated in the study. The only statistically significant finding in regard to self-reported, physician-diagnosed health problems was a dose-response relationship between serum PCB levels and the occurrence of high blood pressure; however, this association failed to achieve statistical significance (p = 0.08) when we controlled for possible confounding effects of both age and smoking. Serum triglyceride and cholesterol levels were also higher in the group with elevated serum PCBs; additionally, there were isolated statistically significant correlations of serum aspartate aminotransferase (SGOT) with serum lipid fraction-adjusted PCB level (r = -0.21) and serum albumin (r = -0.24) and total bilirubin (r = 0.30) with serum PCB level. Although the ranges of serum levels reported herein from exposures to PCBs in the general environment are lower than those that have been associated with acute symptoms or illness in other studies, whether these levels are associated with long-term health risks is not known. Associations of such chronic, low-dose exposures with observable health effects as suggested by this study must be evaluated further before any final conclusions can be drawn.

Environmental Exposure↗
PubMed1986

Society of Gastrointestinal Radiologists Roscoe E. Miller Award. Monitoring hepatic cryosurgery with sonography.

The intraoperative sonographic appearance of frozen hepatic tumors and frozen normal liver was correlated with the histologic appearance of pathologic specimens from six patients. Frozen tissue was visualized as a hyperechoic rim with posterior acoustic shadowing. Normal liver that was frozen and then thawed appeared hypoechoic when compared with normal unfrozen liver. These findings allowed visualization of the extent of freezing in relation to tumor margins. Pathologically, frozen tumors showed definite evidence of necrosis. Normal liver tissue was extremely sensitive to cold and was completely necrotic after freezing. The sonographic appearance of frozen and thawed liver correlated precisely with the gross morphologic and histologic changes seen in the cryolesion. It appears that intraoperative sonography allows accurate monitoring of hepatic cryosurgery.

Carcinoma↗
PubMed1985

Serum dependent variability in the adherence of tumour cells to surgical sutures.

Five commonly used surgical sutures were tested for their abilities to adhere tumour cells by an in vitro adherence assay. Adherence was quantified in vitro using radiolabelled tumour cells after standard incubation with a set length of the differing sutures. Tumour cells consistently adhered least to Prolene. All suture materials tested adhered significantly more tumour cells than Prolene (P less than 0.002 for chromic and less than 0.0001 for nylon, silk and Vicryl when compared with Prolene, with increasing cell numbers adhering to the sutures tested in that order). These differences in adherence were dependent upon an as yet unidentified macromolecule(s) in serum. All of the suture materials supported tumour growth in vivo after pre-incubation with tumour cells. Rapidity of in vivo tumour growth, however, correlated well with the in vitro tumour adherence characteristics of the different suture materials. The clinical significance of these findings is discussed.

Animals↗
PubMed1985

Particle size and surface charge studies of a tin colloid radiopharmaceutical for liver scintigraphy.

The change in particle size of the liver scanning tin colloid radiopharmaceutical (Amerscan) has been determined using the non-perturbing method of photon correlation spectroscopy. Although samples of the tin colloid taken from the preparation vial immediately after preparation and allowed to remain undisturbed in the light scattering cell grow to sizes of ca. 1,200 nm radius, when samples are taken by syringe from the preparation vial at varying times, the particle size is only ca. 400 nm radius. This effect has been shown to be due to shear deflocculation within the syringe needle. Thus, as the tin colloid is always administered in the clinical situation with a syringe, the size of particle which the patient receives is satisfactory for liver uptake. The tin colloid has been shown to be essentially a charge-stabilised colloidal system from measurements of both zeta potential and effect of electrolyte on the flocculation process.

Electricity↗
PubMed1985

Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy.

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.

Adenocarcinoma↗
PubMed1985

The use of carcinoembryonic antigen in the clinical management of patients with colorectal cancer.

It has taken approximately 18 years to define the clinical utility of carcinoembryonic antigen (CEA) as a marker in patients with colorectal cancer. Hopefully, the use of CEA as a prototype and the knowledge of the many clinical studies designed to define its use in patients with colorectal cancer will help avoid the need for 18 years of studies in determining the biologic and clinical applicability of the many promising new candidate tumor markers now being developed. In this paper we will review our own studies which have helped to define the clinical utility of CEA in the care of patients with colorectal cancer.

Carcinoembryonic Antigen↗
PubMed1984

Surgical implications for infusion chemotherapy.

Technical advances that have provided reliable long-term vascular access are described in the setting of pulse and continuous venous chemotherapy infusion and for regional arterial drug delivery. Despite dramatic improvement in the morbidity of such access procedures, it is important to remember that their value still depends upon the effectiveness of the chemotherapy delivered.

Adolescent↗
PubMed1984

Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia.

The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 delta OD450 +/- 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 delta OD450 +/- 147, P less than 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG-CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G-200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti-HLA antisera against the husband's HLA tissue type. In each case, this fraction contained no immunoglobulin or beta-2 microglobulin and was antigenically crossreactive with only one of the husband's HLA haplotypes. The authors believe the PEG-CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor-associated antigens from these complexes which may apply to other solid tumors.

Antigen-Antibody Complex↗
PubMed1984

Effects of tumor growth on interleukins and circulating immune complexes. Mechanisms of immune unresponsiveness.

This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL-1 production by adherent mononuclear cells [AMC]; and IL-2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 X 10(6) W163 ( a dimethylhydrazine [DMH]-induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL-1 and IL-2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P less than 0.05) which correlated with a fall in both IL-1 and IL-2 generation (r = -0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL-1 = 0.9% and IL-2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation.

Adenocarcinoma↗
PubMed1984

The effect of 1,2-dimethylhydrazine (DMH) carcinogenesis on peripheral T cell subsets in the Wistar Furth rat.

1,2-dimethylhydrazine (DMH)-induced colon cancer in Wistar/Furth (W/Fu) rats is analogous in many ways to human colorectal cancer. As part of our attempt to understand the immunobiology of these tumors, we have utilized the recently available monoclonal antibodies W3/25 and OX8 to monitor helper (Th) and suppressor (Ts) lymphocyte subpopulations. Normal untreated male W/Fu rats of less than 1 year of age were phenotyped (n = 43). The mean percentage of Th and Ts was 42 +/- 1 (mean +/- SEM) and 33 +/- 1, respectively. The mean Th/Ts ratio was 1.3 +/- 0.1. A Th/Ts equal to or greater than 1 is considered "normal" in the W/Fu rat. The DMH-treated rats (20 mg/kg/wk) were evaluated in initial experiments at various intervals after treatment. Rats studied 24 hours after a single DMH injection had no alterations in T cell subsets. Rats studied 28, 32, and 65 weeks after the start of 16 weekly DMH injections were found to have a decrease in the percentage of Th and a relative increase in Ts, with Th/Ts ratios of 0.6 +/- 0.2, 0.7 +/- 0.1, and 0.7 +/- 0.1, respectively (each P less than 0.01). In a separate experiment in which rats were studied after 4, 8, and 16 weeks of DMH injections, no alterations in T cell subsets were noted. Rats (n = 5) studied at 20 weeks after the start of DMH were found to have 41 +/- 3% Th and 36 +/- 2% Ts and a Th/Ts ratio of 1.2 +/- 0.1. Three of five rats were found to have adenocarcinomas. Four of five rats had Th/Ts less than 1. One rat with Th/Ts equal to 0.9 had metastatic disease. Rats studied at 25 weeks (n = 8) were found to have more advanced carcinomas (4/8) that were causing obstruction or bleeding in the animal. There was a significant decrease in Th and Ts in this group, with 24 +/- 3% and 26 +/- 3% respectively (P less than 0.001). The Th/Ts ratio for this group was 0.9 +/- 0.1 (P less than 0.01). In other experiments, rats were treated with DMH or placebo over a 16-week period and serially bled during and after treatment. No effect of DMH treatment on T cell subsets was noted. Repeated bleeding alone was noted to cause persistent alterations of T cell subpopulation.(ABSTRACT TRUNCATED AT 400 WORDS)

1,2-Dimethylhydrazine↗
PubMed1984

Patterns of failure after surgical cure of large liver tumors. A change in the proximate cause of death and a need for effective systemic adjuvant therapy.

During a period of 7 years, we have aggressively treated liver tumors whether primary or metastatic. Our experience after 43 curative major liver resections has shown an excellent overall survival: 34 of 43 patients still alive a median of 12 months after liver resection (patient ages ranged from 21 to 85 years, median 57 years). Nineteen patients underwent right hepatic lobectomy, 9 trisegmentectomy, 5 left hepatic lobectomy, 5 extended left hepatic lobectomy, 4 right lobectomy plus left lobe wedge resection, and 1 patient underwent a major hilar wedge resection. Two patients died from sepsis and hepatic failure on or before the 60th postoperative day. One patient with no evidence of recurrent colorectal cancer was lost to follow-up after 2.5 years. One patient died without cancer 12 months after left hepatic lobectomy for colon cancer metastases. Cumulative survival for the entire series and for patients after resection of colorectal cancer metastases was the same: 1 year survival 90 percent; 2 year survival 75 percent, and 3 year survival 65 percent. Seventeen of 30 patients remain disease-free after resection of liver metastases. Of the 13 who had recurrence, 8 are still alive. Ten recurrences were outside of the residual liver (predominantly multiple pulmonary metastases). One recurrence was in the right hemidiaphragm, and only three were in the residual or regenerated liver. Serial carcinoembryonic antigen analysis was the best indicator of recurrence in these 13 patients, 12 of whom were asymptomatic. These data confirm that major liver resection can be performed with minimum postoperative mortality (4.7 percent in this series). More importantly, the majority of patients were cured of their liver metastases. The next goal should be the initiation of adjuvant systemic therapy trials after liver resection in such patients.

Adult↗