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Biomedical subjects

K R Cleary

Publications and source records attributed to K R Cleary.

At least 73 records · Page 4Linked to original sources
PubMed1993

Nonfunctioning islet cell carcinoma of the pancreas.

BACKGROUND: Nonfunctioning islet cell carcinoma of the pancreas has a variable and often indolent natural history, which has resulted in a wide range of treatment recommendations. To more clearly define the natural history and appropriate treatment of this disease, we reviewed our institutional experience over the last 39 years. METHODS: The records of all patients confirmed to have a nonfunctioning islet cell carcinoma of the pancreas were retrospectively reviewed. Kaplan-Meier life tables were constructed and log-rank comparisons were performed. RESULTS: The 73 patients studied had an overall 5-year actuarial survival rate of 50%. Patients with localized disease at presentation (n = 39) had a significantly higher survival rate (p = 0.03) compared with patients with metastatic disease (n = 34). The 19 patients who underwent a potentially curative resection of the primary tumor had a significantly higher survival rate (p = 0.03) compared with the 20 patients with locally advanced, unresectable, nonmetastatic disease. Nine of these 20 patients died of complications of the primary tumor. In contrast, only 2 of 22 cancer-related deaths in the 34 patients with metastatic disease at diagnosis were due to the primary tumor. CONCLUSIONS: (1) Surgical resection should be performed in patients with resectable nonmetastatic disease. (2) Resection of the primary tumor in the presence of metastatic disease is rarely indicated. (3) Innovative treatment strategies are needed for patients with locally advanced, unresectable, nonmetastatic tumors of the pancreatic head.

Adolescent↗
PubMed1993

Colorectal cancer metastasis determined by carbohydrate-mediated cell adhesion: role of sialyl-LeX antigens.

Human colorectal carcinomas with increased metastatic potential and with poor prognosis are characterized by the high content of sialyl-LeX carbohydrate antigens. The levels of these carbohydrate antigens apparently increase during colorectal carcinoma progression from non-metastatic to metastatic tumors. The levels of tumor-associated sialyl-LeX antigens are inversely correlated to the post surgical survival of colon carcinoma patients as revealed by retrospective studies. Cell lines selected for high levels of cell surface sialyl-LeX antigens metastasize to livers when they are injected intrasplenically into nude mice. The highly expressing cells also strongly adhere to activated endothelial cells apparently through E-selectin. We conclude that sialyl-LeX carbohydrate antigen is a unique molecular phenotype that determines colorectal cancer metastasis.

Cell Adhesion↗
PubMed1992

Quantitation of human tumor-reactive monoclonal antibody 16.88 in the circulation and localization of 16.88 in colorectal metastatic tumor tissue using murine antiidiotypic antibodies.

Detection of administered human monoclonal antibodies in the tissues and circulation of patients requires special reagents to overcome interference by normal endogenous immunoglobulin. A practical approach is the development of antiidiotypic antibodies to the human monoclonal antibody and their application in immunoassays specific for the human monoclonal antibody. Accordingly, antiidiotypic antibodies were made to the monoclonal antibody 16.88, a human IgM class anti-colon carcinoma antibody being developed for applications in antibody-targeted immunotherapy of cancer. Three stable clones were obtained that produced antiidiotypic antibodies reactive with 16.88 but nonreactive with human polyclonal IgM or 16.52, a patient-matched IgM monoclonal antibody with different specificity than 16.88. One antiidiotypic antibody, MID 65, was used in a capture format radioimmunoassay to detect 16.88 in the sera of patients who had received 108-mg doses of unlabeled 16.88 coadministered with trace doses of 131I-16.88. Using this assay it was demonstrated that unlabeled 16.88 antibody and 131I-labeled 16.88 antibody did not differ significantly in blood retention for up to 24 h after administration, the period during which the immunoreactivity of the administered antibody remained over 90%. Indirect microautoradiography using exogenously applied 125I-MID 65 to localize 16.88 in frozen metastatic tumor tissue from patients given 16.88 8 days prior to surgery demonstrated the accumulation of 16.88 in areas of apparently healthy tumor cells. Much less 16.88 was detected in stroma or areas of tumor cell necrosis. The accumulation of antibody in nonnecrotic tumor sites encourages the further development of 16.88 for radioimmunotherapy of colon cancer and provides support for further development of human anticytokeratin monoclonal antibodies for cancer therapy.

Animals↗
PubMed1992

Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas.

Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who undergo resection complete multimodality therapy, avoids resection in patients with rapidly progressive disease, and allows radiation therapy to be delivered to well-oxygenated cells before surgical devascularization. Twenty-eight patients with cytologic or histologic proof of localized adenocarcinoma of the pancreatic head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and 50.4 Gy) with the intent of proceeding to resection; all 28 completed this preoperative therapy. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. Our results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.

Adenocarcinoma↗
PubMed1992

Traumatic neuroma of the bile duct causing cholangitis and atrophy of the right hepatic lobe.

Intraluminal traumatic neuromas are an unusual cause of bile duct obstruction. These benign collections of disorganized nerve fibers arise from a bile duct injury during cholecystectomy. Symptoms associated with obstruction or cholangitis may develop decades after the operation. Our patient's neuroma imitated a malignant neoplasm, but the patient has been returned to good health by resection of the right hepatic duct and the atrophic right hepatic lobe.

Aged↗
PubMed1991

Human colonic sulfomucin identified by a specific monoclonal antibody.

Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2-mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid-phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells.

Antibodies, Monoclonal↗
PubMed1991

p53 gene mutations in Barrett's epithelium and esophageal cancer.

Genomic DNA was extracted from archival pathology specimens comprising 10 squamous and 14 adenocarcinomas, including 7 with Barrett's epithelium adjacent to tumor, and corresponding normal esophagus from the resection margin. The polymerase chain reaction was used to amplify selected exons of p53 which were analyzed for mutations using single-strand conformation polymorphism analysis. Mutations were localized to exon 8 for 1 adenocarcinoma and to exon 5 for 1 squamous tumor and 4 of 7 Barrett's specimens. Sequencing confirmed mutations at codons 273 (CGT----CAT; adenocarcinoma) and 176 (TGC----TTC; squamous) and in Barrett's epithelium at codons 152 (CCG----CTG), 155 (ACC----GCC) and 175 (CGC----CAC). Specimens of Barrett's epithelium from separate sites had identical p53 mutations suggesting a clonal origin. Cancers arising in mutant epithelium did not have mutations corresponding to those found in the Barrett's specimens suggesting that other events are required for tumorigenesis.

Adenocarcinoma↗
PubMed1991

Lactose-binding lectin expression in human colorectal carcinomas. Relation to tumor progression.

Lactose-binding lectins having Mr values of approximately 14,000 (L-14.5) and approximately 35,000 Da have been found in a variety of vertebrate tissues, including normal intestine and colon, and in several types of tumors such as colon carcinomas. To determine the clinical relevance of such lectins in human colon cancer, specimens from 46 patients with colorectal carcinoma of identified Dukes' stages were selected and analyzed for the presence and amount of lactose-binding lectins by immunoblotting using a polyclonal, rabbit anti-lectin antibody followed by binding of 125I-labeled anti-rabbit IgG. The amount of a lectin having an Mr value of approximately 31,000 Da (L-31) varied among the specimens. The levels of L-31 lectin in colorectal cancer specimens from primary tumors of patients with distant metastases (Dukes' stage D) were significantly higher than were those from patients without detectable metastases (Dukes' stages B1 and B2). In contrast, among the various specimens the variation in the level of the L-14.5 lectin was smaller, and there was no correlation between the amount of this lectin and cancer stage. Immunohistochemical staining of thin sections of colorectal tumor specimens using antibodies specific for either L-31 or L-14.5 lectin revealed that the two were located at different places, the L-31 lectin primarily within the cytoplasm of carcinoma cells, and the L-14.5 lectin associated with secreted material. These results indicated that the relative amount of the L-31 lectin increases as the colorectal cancer progresses to a more malignant stage.

Colorectal Neoplasms↗
PubMed1991

Plasma cell granuloma of the nasal cavity treated by radiation therapy.

Plasma cell granuloma is a rare, benign tumor most commonly found in the lungs in patients younger than 30 years. Although presentation has been reported at a number of other anatomic sites, this report is the first of plasma cell granuloma of the nasal cavity. The tumor was initially resected, but progression was seen at 1-month follow-up. Because further surgery to completely eradicate the tumor would have been extensive and disfiguring, 40-Gy external beam radiation was given in 20 fractions using a three-field wedge technique. Most recent clinical follow-up at 27 months showed local control. Surgery remains the treatment of choice for plasma cell granuloma when the disease can be completely resected. However, irradiation can also be effective in patients with recurrent or inoperable local disease.

Adolescent↗
PubMed1991

Increased content of an endogenous lactose-binding lectin in human colorectal carcinoma progressed to metastatic stages.

The quantity and localization of two lactose-binding lectins with molecular weights of 31,000 and 14,500 in human colorectal carcinoma tissue specimens obtained by surgical resection have been studied using specific polyclonal antibodies. Electrophoretic separation and blotting of detergent extracts of tumor tissues (48 specimens), followed by the binding of an antibody that recognizes both of these lectins, demonstrated that the contents of Mr 31,000 and 14,500 lectins vary from one specimen to another. The Mr 31,000 lectin content was higher in tumor specimens classified as Dukes' stage D than in those from other stages. A significant correlation was found between Mr 31,000 lectin levels and the levels of carcinoembryonic antigen in the patients' sera at the time of surgery. Immunohistochemical staining with antibodies specific for each lectin was performed with 20 colon carcinoma tissues and 5 colonic adenoma tissues. The results showed that the Mr 31,000 lectin localizes in the cytoplasm of colorectal carcinoma cells and normal epithelial cells, whereas antibody binding to Mr 14,500 lectin is observed in a limited number of carcinoma specimens and is mainly associated with luminal surfaces and secretory products. Adenoma cells were reactive with Mr 14,500 anti-lectin antibody at their luminal surfaces or cytoplasms, but they did not stain with Mr 31,000 anti-lectin antibody. These results suggest that a correlation exists among the level of the Mr 31,000 lectin, the serum level of carcinoembryonic antigen, and the stage of progression of colorectal carcinomas.

Analysis of Variance↗
PubMed1991

Prognostic factors in esophageal squamous carcinoma. A study of histologic features, blood group expression, and DNA ploidy.

The authors studied 69 squamous carcinomas of the middle or lower esophagus to evaluate prognostic factors. Clinical and histologic parameters that were evaluated included weight loss, esophageal obstruction at presentation, site, gross configuration, degree of tumor differentiation, vascular invasion, the status of resection margins, and stage. Blood group antigen (BGA) expression in the tumors was determined immunohistochemically and compared with blood type and antigen reactivity in adjacent normal mucosa. A loss of BGA expression was seen in 27 tumors. This finding was correlated with high stage but was not significantly linked to survival. DNA ploidy was determined by flow cytometry of paraffin-embedded tissues. Forty-one of 52 tumors were aneuploid, and 14 had two or more separate aneuploid populations. However, survival was not correlated with ploidy status. The degree of differentiation and stage of the tumors were the only two independently significant prognostic indicators in this study.

Adult↗
PubMed1991

Mucinous carcinomas of the colon and rectum. An analysis of 62 stage B and C lesions.

The significance of a large extracellular mucinous component in colorectal adenocarcinomas continues to be controversial. We studied 62 stage B and C mucinous carcinomas defined by 60% or greater mucinous component. Sixty of these patients had matched nonmucinous adenocarcinoma controls. Patients with mucinous carcinomas with a residual adenoma had a significantly greater survival than those who did not. Overall, no difference was noted in 5-year survival between patients with mucinous carcinoma and nonmucinous adenocarcinoma (64% each). However, when the stages were considered separately, patients with stage B mucinous carcinoma fared significantly worse and had more local sites of treatment failure. We speculate that patients with stage B mucinous carcinoma may have a worse prognosis owing to the extra-cellular mucin, which may make a complete surgical extirpation more difficult.

Adenocarcinoma, Mucinous↗
PubMed1991

Ectopic expression of mucins in colorectal cancer metastasis.

Cancer metastasis is an ectopic growth of malignant cells. In human colorectal cancer, it is hypothesized that, during the progression of the disease to an advanced stage, highly malignant and metastatic tumor cells arise within primary tumors and become predominant. Based on this hypothesis, molecules associated with metastatic cells have been sought by the comparison of surgical specimens from patients at various clinical stages. Colorectal carcinomas with increased metastatic potential and with poor prognosis have been characterized by a loss of an organ-specific mucin determinant (sulfomucin), by an increased expression of non-intestinal sialomucins, and by an ectopic expression of adhesion ligands (sialyl-dimeric Lex antigens) on mucins.

Adenocarcinoma↗
PubMed1991

Exophytic signet-ring cell carcinoma of the colorectum.

Previous studies have assessed colorectal signet-ring cell carcinomas of the linitis plastica variant but not of the exophytic subtype. We retrospectively reviewed 20 cases of colorectal signet-ring cell carcinoma of the exophytic subtype (greater than 50% signet-ring cells). The patients ranged in age from 14 to 79 years (mean, 51.8 years); 10 were male; 17 were white; and three were black. Ten tumors were colonic (eight, right sided; two, left sided) and 10 were rectal; seven were stage B and 12 were stage C. One patient presented with distant metastases. Eleven of 16 tumors assessed by flow cytometry were diploid. Parenchymal hepatic metastases developed in only two patients. The overall 5-year survival rate was 36%, and matched cases did not vary significantly in survival from typical nonmucinous adenocarcinomas. There was a trend toward poorer survival for patients with advanced-stage tumor. Survival was not affected by primary site, ploidy, presence of vascular/lymphatic invasion or residual adenoma, or percentage of extracellular mucin or signet-ring cells. Our cases were somewhat lower stage than literature cases of signet-ring cell carcinoma of the lintis plastica variant.

Adenocarcinoma, Mucinous↗
PubMed1991

Oncogene activation in esophageal cancer.

We used molecular biology techniques to study the genetic events associated with the development of human esophageal cancer. Point mutations of the p53 tumor suppressor gene were detected in one of 10 squamous cell and one of 14 adenocarcinomas of the esophagus, a frequency that implicates this gene in tumorigenesis. However, the finding of p53 mutations in Barrett's epithelium adjacent to adenocarcinomas may have clinical implications for p53 as a premalignant marker for esophageal cancer.

Adenocarcinoma↗
PubMed1990

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations.

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.

Aged↗
PubMed1990

Metastatic potential of colon carcinoma. Expression of ABO/Lewis-related antigens.

Four monoclonal antibodies specific to various Lewisx-related antigens were tested for binding to monolayers and detergent extracts of the human colon carcinoma cell line HT-29 P and its metastatic variant HT-29 LMM. Only monoclonal antibody FH6 (antisialyl-dimeric Lex) bound more to the metastatic variant compared with HT-29 P. Detergent extracts of human tissues were then assayed for their FH6-binding activity. Normal colonic mucosa displayed less FH6 binding than either Dukes stage B or D primary colon carcinomas. Liver metastases from colorectal carcinoma demonstrated greater binding than stage B and stage D primary tumors, and more than normal liver. Expression of sialyl-dimeric Lex increases as the metastatic potential of colorectal carcinomas increases, and is related to the progression of colorectal cancer.

ABO Blood-Group System↗