A case of an undoubted squamous-cell carcinoma arising at the hepatic flexure in the colon of a middle-aged man is reported. Review of the literature and exclusion of cases not strictly comparable suggest that pure squamous-cell carcinoma of the colon is rare, this being only the fifteenth such tumor reported, and only the second recorded case of such a tumor of the hepatic flexure. Possible pathogenesis is suggested.

Adult↗

PubMedDate not supplied

Further evidence for different isoenzymic forms of a cell surface protease, guanidinobenzoatase, associated with tumours.

Normal colonic epithelial cells possess a cell surface protease referred to as guanidinobenzoatase (GB) and a corresponding cytoplasmic protein inhibitor of GB. Colonic carcinoma cells possess two isoenzymic forms of GB, the normal and the carcinoma specific form, each of which is recognised by the corresponding inhibitors present in the cytoplasm of colonic carcinoma cells. An affinity-purified inhibitor preparation obtained from the cytoplasm of cultured colonic carcinoma cells inhibited these two colonic carcinoma isoenzymic forms of GB but not the GB associated with other forms of tumour. The data suggest that each cell type possessing isoenzymic forms of cell surface GB also possesses the corresponding cell-specific inhibitors of GB.

Carboxylic Ester Hydrolases↗

PubMedDate not supplied

Evidence for distinct isoenzymic forms of a cell surface protease on normal colonic cells and on carcinoma cells from the same colon.

Both normal and carcinoma cells of the colon possess the cell surface protease guanidinobenzoatase (GB). GB is similar to plasminogen activator. In fixed sections, the insolubilised GB can be located by the fluorescent probe 9-amino acridine (9-AA) which binds to the active centre of GB, causing cells possessing active GB to fluoresce yellow. Both cell types possess cytoplasmic proteins which can be extracted in isotonic saline and were shown to inhibit their respective cell surface GB. The formation of an enzyme-inhibitor complex was demonstrated by the failure of 9-AA to react with the cell surface GB inhibitor complex. The data presented indicate that the colonic carcinoma cells possess an isoenzymic form of GB not recognised by the inhibitors of GB extracted from normal colonic cells.

Aminacrine↗

PubMedDate not supplied

The targeting of agmatine-liganded mitomycin C to an enzyme on the surface of tumour cells.

Tumour cells possess a cell surface protease referred to as guanidinobenzoatase (GB). We have synthesised a liganded form of mitomycin C which we refer to as MMC*. This MMC* has the fluorescent properties of mitomycin C and the additional ability to be directed to the active centre of GB by the agmatine moiety of the ligand. We have demonstrated the selective delivery of MMC* to the cell surface of tumour cells possessing active GB by fluorescent microscopy and competition experiments with molecules known to bind to the active centre of GB. The MMC* has a high affinity for tumour cell surface GB and we hope it may have potential in the selective delivery of mitomycin C in the chemotherapy of tumours in vivo.

Agmatine↗

PubMedDate not supplied

Primary adenoid cystic carcinoma of the oesophagus.

The light and electron microscopic appearances of a primary adenoid cystic carcinoma of the oesophagus are described in a 70 year old male patient. A large tumour in the lower third of the oesophagus was resected. The tumour exhibited a polypoid appearance and was histologically identical to the previously described adenoid cystic carcinoma of the oesophagus. The patient died 3 months after surgery from widespread distant metastases. These tumours appear to be more aggressive when they arise in the oesophagus than in the salivary glands.

Aged↗

PubMedDate not supplied

Differential competitive inhibition of a cell surface protease on normal epithelial cells and carcinoma cells of the colon.

The cell surfaces of normal colonic epithelial cells and colonic carcinoma cells both possess a protease referred to as guanidinobenzoatase (GB). Previous studies have shown that these cells possess two distinct isoenzymic forms of GB which could be distinguished by their selective recognition of cytoplasmic protein inhibitors of GB. In the present study we have used competitive inhibitors of GB to demonstrate the differential inhibition of the GB on normal colonic epithelial cells whilst the GB on colonic carcinoma cell surfaces remains active. The enzymic status of GB on these cells has been determined by challenging the treated cells in frozen sections with a second fluorescent inhibitor, followed by fluorescence microscopic analysis.

Aminacrine↗

PubMedDate not supplied

The interactions of protein inhibitors with tumour proteases studied in solution and immobilised on cell surfaces in frozen sections.

The cell surface protease guanidinobenzoatase (GB) has been purified from human colonic and lung carcinoma tissue by an affinity step involving the binding of the enzyme either onto fibrin fibrils or onto agmatine-sepharose. The inhibitor protein (I) was extracted from the cytoplasm of tumour cells and isolated by an affinity step involving the binding of I to GB on the surface of cultured carcinoma cells. The interaction of GB and I in solution was followed by kinetic studies employing the release of the fluorescent 4-methylumbelliferone (MU) from the synthetic substrate 4-methylumbelliferyl-p-guanidinobenzoate (MUGB). The interaction of soluble I with membrane bound GB was followed by using the yellow fluorescent probe 9-aminoacridine (9AA) which binds to active GB but not to GB-I. The results of these studies demonstrated the presence of isoenzymic froms of GB which were recognized specifically by their appropriate isoinhibitor, isolated from the appropriate cell type. This high degree of selectivity suggests a cell specific regulatory role for the inhibitors and the possibility that they might be used for the delivery of cytotoxic molecules to the surface of specific types of tumour cells.

Carboxylic Ester Hydrolases↗

PubMedDate not supplied

Reduced expression of molecules of the cadherin/catenin complex in the transition from colorectal adenoma to carcinoma.

E-cadherin is crucial to the intercellular adherens junctions which are involved in the organisation and maintenance of epithelial structure and suppression of tumour invasion. E-cadherin is associated with the actin cytoskeleton via cytoplasmic proteins, including alpha-, beta- and gamma-catenins, which together form the cadherin/catenin complex. To evaluate changes of the molecules of the cadherin/catenin complex in colorectal carcinogenesis, seventy-four sporadic adenomas, samples of histologically normal epithelium adjacent to 65 adenomas, and 52 carcinomas arising in adenomas were investigated by immunohistochemistry. All normal epithelial cells showed a uniform membranous staining pattern for E-cadherin, alpha-, beta-, and gamma-catenin. Decreased expression of all 4 proteins occurred in parallel in adenomas and carcinomas (in all cases, p < 10(-5). Decreased expression of the cadherin/catenin complex in adenomas was associated with increasing severity of dysplasia (p < 0.001, for E-cadherin, alpha-, and gamma-catenin, p < 0.005 for beta-catenin). Carcinomas displayed significantly reduced expression of the cadherin/catenin complex compared with their associated adenomas (all p < 0.001). The results directly confirm that colorectal tumour progression and invasion is associated with disruption of the cadherin/catenin complex and suggest that the genetic changes and transcriptional modulation of catenins underlying this progression may affect all members of the complex.

Adenoma↗