Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor cell lysis can be enhanced significantly in vitro when heteroconjugate (HC) antibodies (anti-CD3 x anti-tumor mAb) are used to specifically direct lymphocyte effector cells to the tumor cell target. In order to effectively utilize HC antibodies in an immunotherapy protocol, methods must be identified for the optimum expansion, activation, and retargeting of lymphocyte-effector populations from cancer patients. In this study, we have compared the proliferative responses of different normal and renal cell carcinoma (RCC) patient lymphocyte preparations (PBL, tumor-infiltrating lymphocytes) stimulated in vitro for periods up to 12 days with a variety of growth factor combinations (anti-CD3, rIL-2, rIL-4). These activated lymphocyte preparations were then tested in vitro for their ability to kill RCC tumor cells and tumor cell lines in the presence of HC preparations (anti-CD3 mAb covalently linked to mAb reactive to different RCC tumor-associated Ag). RCC patient PBL cultured with anti-CD3 plus rIL-2 for 12 days resulted in a 3- to 160-fold expansion of effector cells. These cells, as well as tumor infiltrating lymphocytes, when retargeted with appropriate HC antibodies were capable of mediating high levels of killing of autologous tumor cells. No constitutive autologous anti-tumor cell response was detected in the absence of added HC antibodies. Of the five anti-RCC mAb tested (A6H, K29, K20, UR07, and URO 3), HC containing URO 3 x anti-CD3 and K20 x anti-CD3 elicited the highest level of tumor cell lysis by the activated lymphocyte effector cells. Together these results demonstrate that HC antibodies may be a useful imunotherapeutic reagent for directing the killing of RCC tumor cells by autologous lymphocytes.
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PMID:Heteroconjugate antibody-directed killing of autologous human renal carcinoma cells by in vitro-activated lymphocytes. 213 77

With a view to increasing drug incorporation without loss of antibody activity, tritium-labeled methotrexate (MTX) was covalently linked to a polyclonal rabbit IgG antibody against bovine serum albumin and a monoclonal mouse IgG antibody against human renal cancer (Dal K20) by a site-specific method based on hydrazone bond formation between MTX hydrazide and the aldehyde groups generated by periodate oxidation of carbohydrate moieties in IgG (which are uncommon in the antigen-binding region). These conjugates were compared with the corresponding non-site-specific MTX-IgG conjugates produced by the N-hydroxysuccinimide active-ester method with regard to synthesis, stability, retention of antibody activity, inhibition of the target enzyme dihydrofolate reductase and antitumor effect. Incorporation levels achieved with the hydrazide method were no greater than with the active-ester method, typically 6-7 mol MTX/mol IgG. Approximately the same dihydrofolate-reductase-inhibitory capacity was observed for MTX bound by either method. Hydrazide conjugates lost bound drug more rapidly than active-ester conjugates on freezing and thawing, on incubation at 37 degrees C and 51 degrees C, and in the presence of serum or rat liver homogenates. Exposure to rat liver homogenates at 37 degrees C, pH 4.6, for 24 h led to the loss of 50%-60% of the bound drug from hydrazide conjugates compared to 20%-30% from the active ester conjugates. Bio-Gel P-2 chromatography of low-molecular-mass fractions, obtained after exposure of each of the conjugates to liver homogenates, revealed the presence of a compound that had the same elution volume and RF on thin-layer chromatography as free MTX. Enzyme-linked immunosorbent assay showed loss of antibody activity of both types of conjugates at 51 degrees C and on freezing and thawing. In a clonogenic assay, the active-ester conjugate of Dal K20 appeared to be equally effective or slightly better as a tumor inhibitor than the corresponding hydrazide conjugate. The hydrazide method may be useful in linking MTX to those monoclonal antibodies that tend to denature when subjected to the active-ester method of linkage.
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PMID:Synthesis of site-specific methotrexate-IgG conjugates. Comparison of stability and antitumor activity with active-ester-based conjugates. 278 96

Three IgG1 monoclonal antibodies derived from BALB/c mice immunized with the Caki-1 human renal cell carcinoma (RCC) line react with antigens present in most human RCCs but restricted in their expression in normal adult tissues. Antibody DAL-K20 reacted with five of six RCCs and the lining epithelium of normal proximal and distal convoluted tubules. Antibody DAL-K29 reacted with eight of nine RCCs, with glomeruli, where it outlined the capillaries, and more weakly with prostatic glandular epithelium and the basal layer of the epidermis. K29 precipitated molecules with molecular weights of 118,000 and 150,000 from extracts of surface-labeled Caki-1 cells. Antibody DAL-K45 reacted with four of six RCCs but not with any normal adult tissue including kidney. It precipitated Mr 177,000 and 150,000 antigens. The three antibodies showed distinct patterns of reactivity with human tumor cell lines.
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PMID:Monoclonal antibodies to kidney and tumor-associated surface antigens of human renal cell carcinoma. 353 Apr 41

Intermediate filaments (IFs; diameter, about 10 nm) are cytoplasmic cytoskeletal structures found in most vertebrate cells. Their protein subunits comprise a large multi-gene family of related proteins, which make it possible to divide IFs into seven separate classes whose expression is cell-type-dependent. The most important IF classes are cytokeratin (CK) filaments (epithelial cells), vimentin filaments (mesenchymal cells), desmin filaments (muscle cells), glial filaments (astrocytes), and neurofilaments (nerve cells). As the specificity of expression of IF proteins is retained in malignant tumors, they are suitable as histological markers of differentiation (tumor markers). The protein subunits of the epithelial CK filaments are unusually diverse, and within the various types of epithelia, their expression is differentiation specific. Until recently, the catalog of human CKs comprised 19 related, yet distinct polypeptides (CKs 1-19; Moll et al., 1982a); CK 20 can now be added to this list. On the basis of sequence relationships, two CK subfamilies can be delineated (CKs 9-20 = type I; CKs 1-8 = type II). Any given epithelial cell exhibits a characteristic, differentiation-dependent combination of two or more CK polypeptides, with type-I and -II polypeptides always occurring in stoichiometric amounts (i.e., as "pairs"), because the basic structural unit of the CK filaments is a heterotypical tetramer complex. On the basis of their main tissue distribution patterns, it is possible further to subdivide these polypeptides into CKs typical of stratified squamous epithelia (CKs 1-6, 9-17) and those typical of simple columnar epithelia (CKs 7, 8, 18-20); these CKs exhibit differential expression patterns in the various types of squamous and columnar epithelia. The actual characterization of the novel CK 20 as a CK initially proved to be rather difficult, as this cytoskeletal protein, which can be biochemically isolated from cells of the intestinal epithelium (M(r) 46,000; previously called "IT protein"), exhibits no reaction with numerous well-known CK antibodies in Western blots. However, a series of other characteristics typical of CKs could be demonstrated. Thus, IT protein was found, in vitro (nitrocellulose-blot binding test, native gel electrophoresis), to for heterotypical complexes with the type-II CK 8, and these complexes were able to reconstitute themselves into typical IFs in vitro. Chymotrypsin-cleaving experiments revealed the presence of a resistant core fragment (M(r) 38,000), indicating a alpha-helical "coiled-coil" conformation typical of IFs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cytokeratins as markers of differentiation. Expression profiles in epithelia and epithelial tumors]. 750 60

Inverted papilloma (transitional cell papilloma, inverted type) is a rare, benign urothelial tumor. The distribution of cytokeratin (CK) expression in 22 cases was investigated and compared with normal urothelium and urothelial carcinomas: CK7/8, basal increased positivity; CK13, diffuse positivity; CK18, loss of intensity and loss of umbrella cell staining; CK19, reduction of positivity; CK20, reduction of umbrella cell staining. The data indicate that the inverted papilloma is a basal cell urothelioma.
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PMID:[Cytokeratins in inverted papillomas of the urinary bladder. (Part 1.)]. 751 66

Cytokeratins, which comprise a multigene family of 20 related polypeptides (CKs 1-20), are constituents of the intermediate filaments of epithelial cells, in which they are expressed in various combinations depending on the epithelial type and the degree of differentiation. Of these, CK 19 (400 amino acids; 44.1 kilodaltons) is an example of a widely distributed CK, being expressed in various epithelia, including many simple epithelia. In contrast, the recently identified CK 20 (424 amino acids; 48.6 kilodaltons) is essentially confined to gastrointestinal epithelia, the urothelium and Merkel cells. The differential expression of individual CKs in various types of carcinomas makes them useful markers for histopathological carcinoma subtyping, providing relevant information concerning the differentiation and origin of carcinomas, especially when tumors first present as metastases. The CKs that are of particular value for differential diagnosis include CK 20, as it is mainly expressed in carcinomas derived from CK 20-positive epithelia; it is also found in bile-tract, pancreatic and mucinous ovarian adenocarcinomas, being absent in most other carcinomas. In certain carcinoma types, the changes in the expression of individual CKs that may occur during tumor progression could be of prognostic relevance. It remains to be established whether the serological detection of fragments of not only widely distributed but also more restrictedly expressed CKs may provide useful serological tumor markers in the future.
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PMID:Cytokeratins in the histological diagnosis of malignant tumors. 752 43

Keratin 20 is a recently identified keratin protein distributed particularly in the epithelial cells of the gastrointestinal tract. In this study, keratin 20 was immunohistochemically evaluated in 788 epithelial tumors of different organs. Keratin 20 was consistently present in colonic adenocarcinomas and their metastases in lymph nodes, liver, lung, and ovaries; most primary and metastatic colon carcinomas showed high numbers of positive cells independent of their level of differentiation. Adenocarcinomas of the upper gastrointestinal tract, pancreas, and cholangiocarcinomas showed variable reactivity. Hepatocellular carcinomas and carcinoid tumors often showed focal reactivity limited to scattered tumor cells. In contrast, keratin 20 was virtually absent in primary adenocarcinomas of lung, ovaries, and endometrium. Notable exceptions among ovarian tumors were the mucinous neoplasms that showed variable, sometimes significant keratin 20 reactivity. Transitional cell carcinomas irrespective of grade were usually positive, whereas most prostatic and renal adenocarcinomas were negative or showed only single positive cells. Typically negative were squamous cell carcinomas of all organs and carcinomas of the breast. Merkel cell carcinomas of the skin showed consistent reactivity, whereas small cell carcinomas of the lung were negative. On the basis of these observations, keratin 20 seems to be a suitable adjunct marker to evaluate the primary origin of carcinomas in specific contexts, especially to separate adenocarcinomas of gastrointestinal versus nongastrointestinal origin.
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PMID:Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. 756 35

Using a commercially available monoclonal antibody (Ks20.1) and the avidin-biotin peroxidase method on cytospins and cell blocks, we analyzed cytokeratin (CK) 20 expression in 169 serous effusions. Cytoplasmic staining was observed in 44/151 malignant fluids. Colon, gastric, and pancreatic adenocarcinomas and mucinous ovarian tumors were most frequently positive. Single cases of transitional-cell and squamous cell carcinomas were reactive as well. Lung and breast cancers were mostly negative. Nonmucinous ovarian tumors were invariably unlabeled as were mesotheliomas and normal mesothelial cells. The study shows that CK 20 is valuable in distinguishing tumor cell origin in effusions. In particular, it identifies a set of carcinomas with the majority arising from the gastrointestinal tract, and represents a highly characteristic marker for colorectal cancer.
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PMID:Utility of cytokeratin 20 in identifying the origin of metastatic carcinomas in effusions. 765 55

The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nervus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cell carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.
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PMID:Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene. 884 Jan 59

The bel-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nevus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cel carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.
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PMID:Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene. 873 19


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