PubMed Health⌕ Search

Biomedical subjects

G D Steele

Publications and source records attributed to G D Steele.

At least 73 records · Page 4Linked to original sources
PubMed1989

Detection of the tumor-associated glycoprotein antigen (TAG-72) in premalignant lesions of the colon.

We used monoclonal antibody B72.3 to study the expression of the colorectal carcinoma-associated antigen TAG-72 in premalignant colonic lesions with the immunoperoxidase technique. This antigen, which is rarely detectable in the normal colonic epithelium, was expressed in 13 of 19 adenomas with moderate to severe dysplasia and nine of nine cases of inflammatory bowel disease. The antibody reacted with the normal-appearing mucosa adjacent to a carcinoma in 10 of 12 cases, although only eight of the tumors expressed the antigen. The expression of the TAG-72 antigen in the colonic epithelium may be an early marker of malignant transformation.

Antibodies, Monoclonal↗
PubMed1989

Aberrant mitochondria in two human colon carcinoma cell lines.

Electron micrographs of CCL237 and FET cells (two slowly growing, differentiated human colon carcinoma lines) revealed enlarged mitochondria with few cristae. Polarographic measurement of respiratory activity in mitochondria isolated from these cell lines was compared to that of CV-1 cells (a normal monkey kidney epithelial line) and MIP101 cells (another human colon carcinoma line), both of which have mitochondria with a "normal" appearance. The respiratory control ratios of CCL237 and FET mitochondria were found to be considerably lower than those of CV-1 and MIP101 mitochondria (approximately 3 as compared to greater than 10, respectively), indicating that in CCL237 and FET mitochondria the processes of substrate oxidation and phosphorylation of ADP are only loosely coupled. In intact cells, differences in radiolabeled tetraphenylphosphonium uptake showed that the mitochondrial membrane potential in CCL237 and FET cells was less than that in CV-1 and MIP101 cells, and that nigericin failed to hyperpolarize the mitochondria of CCL237 and FET cells. In addition, FET mitochondria exhibited significantly lower ADP-stimulated and uncoupled respiratory rates than mitochondria isolated from the other cell types, indicating that in the former, the capacity for oxidative phosphorylation is somehow impaired. Selective toxicity of FET cells was obtained by treatment with 2-deoxyglucose, an inhibitor of glycolysis, suggesting the possibility of exploiting the phenotype of impaired oxidative metabolism for chemotherapy.

Animals↗
PubMed1989

Relationship between extracellular matrix interactions and degree of differentiation in human colon carcinoma cell lines.

Human colon carcinoma cell lines that vary in their degree of differentiation were examined for their ability to interact with extracellular matrix components. For this purpose, established cell lines were classified on the basis of several criteria that relate to degree of differentiation. These criteria include histology of the original tumor, histology of xenografts, in vitro morphology, and carcinoembryonic antigen expression. On this basis, the cell lines used were either moderately well or poorly differentiated. The poorly differentiated cell lines adhered to surfaces coated with laminin or reconstituted basement membrane extract (Matrigel) to a significantly greater extent than the moderately well differentiated lines with the exception of one moderately well differentiated line that was derived from a highly aggressive signet ring cell carcinoma. In addition, the poorly differentiated cell lines exhibited considerable spreading on laminin and Matrigel after adherence that was not evident for the moderately well differentiated lines. The adherence of these cell lines on fibronectin-coated surfaces did not correlate as well with differentiation although, in general, poorly differentiated cell lines adhered better than moderately well differentiated lines. None of the cells that adhered to fibronectin exhibited the extensive spreading seen on laminin. The specificity of tumor cell interactions with extracellular matrix glycoproteins was examined using synthetic peptides which correspond to sequences within these proteins that are recognized by cell surface receptors. The pentapeptide YIGSR-NH2 significantly inhibited the adherence and spreading of the tumor cell lines on laminin, but not on fibronectin. The peptide RGDS, however, did not inhibit tumor cell interactions with laminin although it did inhibit their interactions with fibronectin. Thus, the interactions of colon carcinoma cells with laminin and fibronectin are probably mediated by separate receptors. Taken together, the data demonstrate that cells derived from colon carcinomas exhibit considerable variation in their ability to interact with extracellular matrix components, and that this variability is related to the degree of differentiation of original tumor.

Carcinoembryonic Antigen↗
PubMed1989

Natural killer sensitivity of colorectal carcinoma targets. Correlation with degree of differentiation.

Lymphocytes with natural killer (NK) ability recognize a wide range of target cells; however, the mediators of specific target recognition are still largely unknown. Despite the diversity of the NK target repertoire, it is typified by cells of relatively immature phenotype. The purpose of this study was to determine if colorectal carcinoma (CRC) targets were sensitive to spontaneous lysis by fresh human NK effector cells and to observe the role of CRC differentiation in this process. Results demonstrated that poorly differentiated CRC targets were susceptible to NK-mediated lysis whereas CRC targets with more differentiated structure were NK resistant. In addition, chemical induction of a more mature CRC phenotype confers NK resistance on a previously NK-susceptible target. This maturation-related modulation of NK sensitivity can provide a model with which to further study interaction between NK cells and CRC targets.

Butyrates↗
PubMed1989

Interactions of human colorectal carcinoma cells with basement membranes. Analysis and correlation with differentiation.

The abilities of colorectal carcinoma cell lines to adhere and invade through a basement membrane were examined. The four poorly differentiated cell lines studied were three to four times more adherent and spread to a greater extent following adherence to a basement membrane matrix than the three moderately well-differentiated (MWD) lines. One exception was the MWD cell line DLD-2, whose histologic features resembled a signet ring carcinoma. The ability of these cells to invade through a basement membrane model was measured. This assay showed that the poorly differentiated cell lines as well as DLD-2 were three times more invasive than the remaining MWD cell lines. These data indicate that tumor cell adherence can be correlated with invasion through basement membranes. In addition, the ability of colorectal carcinoma cells to interact with the basement membrane seems, in general, to be inversely related to the degree of cytodifferentiation.

Basement Membrane↗
PubMed1989

Experience with colorectal carcinoma metastatic to the liver.

The predilection of colorectal cancer metastases for the liver is probably the result of several factors, including the blood supply, the "homing" characteristics of the tumor cells, and the state of the liver. Five-year survival rates after hepatic resection for colorectal cancer metastases range from 20 to 40 per cent, and some other patients obtain palliative benefit. The authors discuss the three presentations of liver metastases, operative techniques, and prognostic factors.

Colorectal Neoplasms↗
PubMed1989

Hepatic cryosurgery.

Cryoablation of liver metastases from colorectal and neuroendocrine tumors was accomplished in 20 patients using liquid nitrogen delivered through insulated probes. Intra-operative ultrasound was used to detect liver metastases and to monitor freezing and thawing. Tumor response was evaluated by histologic examination, CT, and serum tumor markers. This study established the safety and technical feasibility of hepatic cryosurgery and provided guidelines for treating liver tumors of diverse origins.

Adult↗
PubMed1989

The expression of colorectal carcinoma-associated antigens in the normal colonic mucosa. An immunohistochemical analysis of regional distribution.

Immunohistologic studies were performed to evaluate the expression and regional distribution of 20 colorectal carcinoma-associated antigens in the colonic mucosa of 12 normal adults. A distinct regional variation was seen in the expression of blood group A, B, Lewis(b), and extended Lewis(y) antigens, which were expressed predominantly in the right colon, whereas Lewis(a), Lewis(y), and H-type 2 were prevalent throughout. Lewis(x) and X-like antigens were only occasionally expressed. Two antibodies against sialylated Lewis(a) showed different staining patterns, with CA19.9 positive in only two biopsies and CO29.11 intensely positive in most. Two of the three antibodies detecting carcinoembryonic antigen epitopes (3d6 and COL-4) stained many biopsies, whereas COL-12 was rarely detected. No regional gradient was found in the expression of the other antigens studied (B72.3, ME491; GA73.3, ND1, and ND4). This mapping data will provide an important baseline for future studies of epitope distribution in the colon in premalignant and neoplastic conditions.

ABO Blood-Group System↗
PubMed1988

Increased mRNA expression of a laminin-binding protein in human colon carcinoma: complete sequence of a full-length cDNA encoding the protein.

Reliable markers to distinguish human colon carcinoma from normal colonic epithelium are needed particularly for poorly differentiated tumors where no useful marker is currently available. To search for markers we constructed cDNA libraries from human colon carcinoma cell lines and screened for clones that hybridize to a greater degree with mRNAs of colon carcinomas than with their normal counterparts. Here we report one such cDNA clone that hybridizes with a 1.2-kilobase (kb) mRNA, the level of which is approximately equal to 9-fold greater in colon carcinoma than in adjacent normal colonic epithelium. Blot hybridization of total RNA from a variety of human colon carcinoma cell lines shows that the level of this 1.2-kb mRNA in poorly differentiated colon carcinomas is as high as or higher than that in well-differentiated carcinomas. Molecular cloning and complete sequencing of cDNA corresponding to the full-length open reading frame of this 1.2-kb mRNA unexpectedly show it to contain all the partial cDNA sequence encoding 135 amino acid residues previously reported for a human laminin receptor. The deduced amino acid sequence suggests that this putative laminin-binding protein from human colon carcinomas consists of 295 amino acid residues with interesting features. Containing only two cysteine residues, the protein does not have consensus sequences for asparagine-linked glycosylation, amphipathic alpha-helix, or the N-terminal leader signal sequences for entry into endoplasmic reticulum, although hydrophobic segments for potential membrane associations exist. There is an unusual C-terminal 70-amino acid segment, which is trypsin-resistant (no lysine or arginine) and highly negatively charged (13 aspartic plus glutamic residues). Within this segment are five repeats of (Asp/Glu)-Trp-(Ser/Thr); two of these are nearly tandem repeats of Thr-Glu-Asp-Trp-Ser-Ala-Xaa-Pro.

Amino Acid Sequence↗
PubMed1987

Laminin expression in colorectal carcinomas varying in degree of differentiation.

We are studying the ability of colorectal carcinomas, which vary in degree of differentiation, to assemble a basement membrane and the relationship between differences in this ability and perturbations in laminin expression. For these studies, we are using human colorectal carcinoma cells grown both in vitro and in nude mice as well as tumors obtained at surgery. Immunoperoxidase staining of human tumors indicates that laminin is present in a defined basement membrane in moderately to well-differentiated tumors. This staining pattern is absent in poorly differentiated tumors. In these tumors, staining is discontinuous and sometimes observed intracellularly. The laminin synthesized by in vitro cells was immunoprecipitated and analyzed by acrylamide electrophoresis. Neither poorly nor well-differentiated carcinoma cells exhibit marked differences in the rate of synthesis of laminin. Differences are present in the rate at which newly synthesized laminin is secreted. These differences may result from alterations in posttranslational processing. Such alterations may contribute, along with other factors, to the inability of poorly differentiated tumors to make a basement membrane.

Animals↗
PubMed1987

Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation.

Positively charged lipophilic compounds, such as rhodamine 123, localize in mitochondria and are selectively accumulated and retained by carcinoma cells. It has been suggested that this phenotype may be exploited for selective killing of carcinoma cells by lipophilic cations. Here we report that doubly positively charged dequalinium, which has been used for 30 years as an antimicrobial agent in over-the-counter mouthwashes, lozenges, ointments, and paints, exhibits significant anticarcinoma activity. Dequalinium is more effective than seven of eight established anticancer drugs in prolonging the survival of mice with intraperitoneally implanted mouse bladder carcinoma MB49. Dequalinium also inhibits the growth of subcutaneously implanted human colon carcinoma CX-1 in nude mice and recurrent rat colon carcinoma W163 in rats. Lipophilic cationic compounds, such as dequalinium, could comprise a unique class of anticarcinoma agents.

Animals↗
PubMed1987

Isolation and characterization of an undifferentiated human colon carcinoma cell line (MIP-101).

An undifferentiated human colon carcinoma cell line was established from tumor tissue obtained from metastasis to the liver of colonic adenocarcinoma in a patient with fulminant Dukes D colorectal carcinoma. Histological analysis of the tumor biopsy from the liver confirmed the hospital pathology report of poorly differentiated colonic adenocarcinoma. Explants of this tumor tissue xenografted into a nude mouse were used to establish an epithelioid-like cell culture line, MIP-101. The cell line formed tumors in nude mice that histologically appeared undifferentiated and did not stain for carcinoembryonic antigen (CEA). No CEA was present either by radioimmunoassay (RIA) of the culture supernatant or by immunoperoxidase staining of the tumors or monolayers. MIP-101 appears to be one of the most undifferentiated human colon carcinoma cells lines available. It should prove useful in the search for markers of undifferentiated colonic cancer and in studies of colonic cancer differentiation.

Adenocarcinoma↗
PubMed1986

Abdominal pain in neutropenic cancer patients.

A review of 58 patients with malignancies (age range, 14-73 years), who required surgical consultation for acute abdominal pain in the setting of neutropenia (granulocyte count less than 1000/mm3) after chemotherapy was conducted. Ninety percent had fevers greater than 37.8 degrees C, 30% had diarrhea or melena, and 25% had diminished bowel sounds. Five of the 29 patients (17%) with localized pain had surgical intervention; 3 of 29 patients (10%) with generalized pain underwent operations (2 for x-ray findings). All eight of these surgically treated patients survived to leave the hospital. Eighteen of the 29 patients with generalized pain were believed to have a similar syndrome of diarrhea (occasionally heme positive) and diffuse abdominal tenderness (some with peritoneal signs and distension), which was termed "neutropenic enteropathy." Eleven of these 18 patients had their symptoms resolve with antibiotic therapy, aggressive fluid replacement, and a return of their granulocyte count to normal. The other seven died of pneumonia (two), unknown causes (one), and diffuse enterocolitis throughout the intestinal tract (four documented at autopsy). The overall 30-day mortality rate in this series was 34%. Several factors correlated significantly with mortality: hypotension at the onset of pain (80% mortality), bacteremia (63% mortality), and fungemia (100% mortality). Absolute leukocyte count and absolute platelet count did not correlate with mortality. This study reaffirms that patients with neutropenic enteropathy are best treated conservatively. Patients with surgically correctable disease were identified by specific focal findings on examination or x-ray.

Abdomen↗
PubMed1986

Serial levels of CA 19-9 and CEA in colonic cancer.

The use of serial carbohydrate antigen (CA) 19-9 assays was assessed by comparison with serial carcino-embryonic antigen (CEA) levels on the plasmas of 53 patients with colorectal carcinoma. The patients had all undergone resection for their primary tumors and in six instances subsequent resections for hepatic metastases. Initial CA 19-9 levels were greater than or equal to 37 U/mL in 22 of the 53 patients (41%) and in 68% of the patients with metastatic disease. Similar trends of serial CA 19-9 and CEA levels were found in 79% of the 53 patients. One patient with initially normal CEA levels had elevated CA 19-9 levels from the start. In ten of the 53 patients (19%), serial CA 19-9 levels remained low despite tumor recurrence or progression, and despite increasing CEA levels above 5 ng/mL. The increasing serial CEA trends predicted recurrence in 88% and increasing CA 19-9 trends in 50% of cases, which was increased to 70% by including trends of CA 19-9 levels below 37 U/mL. Following hepatic lobectomy, both serial CEA and CA 19-9 levels decreased rapidly. Used alone, serial CA 19-9 levels did not appear to be as sensitive as standard CEA in this retrospective study of selected patients.

Adult↗
PubMed1985

Colorectal carcinoma in patients under age 40.

Patients under the age of 40 with colorectal cancer (29 females, 18 males) were compared with similar patients in our general hospital population and analyzed for patterns of presentation, stage at diagnosis, degree of tumor differentiation, and survival. There was a higher incidence of poorly differentiated tumors in the young patients (21% vs. 8% in the general population). Colon cancer in young adults was in a more advanced stage at presentation. The survival rate for young patients was 23% vs. 61% for the general population (p = 0.02). Stage C patients treated for cure had a survival rate of 56% in the general population compared with 34% in young adults (p = 0.05). The degree of tumor differentiation did not affect survival in those young patients undergoing curative resections (41% for well-differentiated and 30% for poorly differentiated cancers, p = 0.09). The median survival time by stage was: Stage A and B (N = 3) 36 months, Stage C (N = 26) 32 months, and Stage D (N = 18) 15.8 months. The need for early recognition of colorectal cancer in young adults is emphasized by the greater incidence of advanced disease and the high failure rate.

Adult↗
PubMed1984

Current treatment of metastatic renal cell carcinoma with xenogeneic immune ribonucleic acid.

In 1979 we reported a phase I trial involving 6 patients treated with immune ribonucleic acid for renal cell carcinoma. Since that report 27 patients with stage III or IV renal cell carcinoma have been assessed in a phase II trial. All patients have undergone excision of the primary tumor or superficial metastases, injection of tumor into guinea pigs and harvesting of immune ribonucleic acid. Autologous lymphocytes, obtained by plasmapheresis on an outpatient basis, have been incubated with immune ribonucleic acid and reinfused into the host. Results indicate complete response in 1 patient for more than 61 months, partial response in 5 patients for 6 to 10 months and stabilization in 10 patients for 2 to 8 months, all of whom had progressive disease before the institution of therapy. Six patients with continued progressive disease died at a median of 2 months after therapy. Of 5 patients treated in an adjuvant fashion only 1 has had a relapse from 9 to 18 months after therapy. Patients with pulmonary metastases seem to represent the most favorable group for this passive form of immunotherapy. This therapy would seem to offer reasonable alternatives in selected patients with advanced disease.

Adenocarcinoma↗
PubMed1983

Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump.

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.

Adult↗