Occupational exposure to vinyl chloride and risk of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common form of cancer that arises from hepatocytes and whose risk may be affected by several known factors, including viruses, alcohol, cigarette smoking, and several genetic conditions. Liver angiosarcoma is a rare cancer that develops from endothelial cells and whose most relevant known risk factor is occupational exposure to vinyl chloride (VC). Since occupational exposure to high levels of VC may still occur, we reviewed the epidemiological and experimental evidence supporting the notion that inhalation exposure to VC is a risk factor for HCC. We find that available epidemiological evidence is based on a dose-risk study with 10 HCC cases and on a partially overlapping study reporting similar results: neither study provided controls for known non-occupational confounders for HCC. Carcinogenesis bioassays of VC inhalation in rodents indicate that angiosarcomas account for nearly all liver tumors induced. Thus, the role of inhalation exposure to VC in HCC risk remains unclear, awaiting further studies and the integration of results from epidemiological studies and animal models.     

Occupational exposure to vinyl chloride and cancer risk: a review of the epidemiologic literature.

Occupational exposure to vinyl chloride (VC) is causally related to liver angiosarcoma, whereas there is inconsistent epidemiologic evidence for other neoplasms. Two pooled analyses of worker cohorts from 56 plants in North America and Europe provide the most comprehensive and updated data on cancer risk among workers exposed to VC. These included over 22,000 workers, with a total of 640,000 person-years of observation, followed-up for up to 50 years. Overall, a total of 1,778 cancer deaths were observed versus 1,829.46 expected, corresponding to a standardized mortality ratio (SMR) of 0.97 (95% confidence interval (CI)=0.93-1.02). Excluding 71 confirmed angiosarcomas, there were 60 deaths from liver cancers versus 44.35 expected (SMR=1.35, 95% CI=1.03-1.74). Lung and laryngeal cancer mortality were significantly lower than expected (SMR=0.88 and 0.59, respectively). The SMRs for soft tissue sarcoma, brain, lymphoid and haematopoietic system cancers were not materially different from unity. Thus, the aggregate data from over 20,000 VC workers in North America and Europe exclude any excess mortality from lung, laryngeal, soft tissue sarcoma, brain, lymphoid and haematopoietic neoplasms. There appears to be a slight excess of liver cancer other than angiosarcoma, which is difficult to interpret and is likely due to residual misclassification of angiosarcomas.     

Development of monoclonal antibodies to human tumor markers

The development of hybridoma technology has provided the possibility of preparing unlimited amounts of highly specific and homogeneous monoclonal antibodies thus eliminating many of the disadvantages with conventional antisera and rekindling interest in the application of immunodiagnostic and immunotherapeutic approaches to human cancer. Several reports, including our own of monoclonal antibodies to tumor-associated antigens expressed by solid tumors including gastric, colorectal, lung and other various carcinomas, were reviewed from the viewpoint of tumor markers.     

Immunohistochemical techniques in the early screening of monoclonal antibodies to human colonic epithelium

Selected monoclonal antibodies (McAbs) isolated after immunization of rats with a human colonic carcinoma membrane preparation, have been screened on frozen and paraffin sections of colonic tissue, using immunohistochemical techniques, in order to provide additional information with regard to specificity and crossreactivity with normal tissues.     

Development and identification of monoclonal antibodies against ractopamine

Ractopamine was reacted with two carrier proteins, human serum albumin and bovine thyroglobulin, as immunogen and coating antigen, respectively. Using a conventional immunization protocol, we generated a stable murine monoclonal antibody toward ractopamine, which had high affinities. The clone was found to be of IgG(2a) subclass with kappa light chain. An indirect competitive enzyme-linked immunosorbent assay for the determination of ractopamine has been optimized and characterized. The sensitivity, estimated as the IC(50) value, was 21.25 ng/mL, with a practical working range between 2.9 and 450 ng/mL. The limit of detection was 1.5 ng/mL. Moreover, other phenethanolamine beta-agonists showed low cross-reactivity with the monoclonal antibody. In addition, the indirect competitive enzyme-linked immunosorbent assay for the detection of ractopamine in animal feed was also developed using this antibody.     

Development and identification of monoclonal antibodies against parathion

An amino-derivative of parathion was prepared and conjugated to human serum albumin (HSA) and bovine thyroglobulin (BTG) via diazonium condensation. Spleen cells producing high titer antibody were removed and fused with myeloma cells of SP2/0 origin. Using a conventional immunization protocol, we generated nine stable murine monoclonal antibodies (MAbs) producing cell lines to parathion. After four successive limiting dilutions, antibodies produced by nine clones had high affinities, ranging from 10(9) to 10(12) M(-1). These clones were found to be of IgG class and IgM class with k light chain. Subclass determination showed that the clones produced IgG(1), IgG(2a), IgG(2b), and IgM types of antibody. One clone (2H(9)) was used to establish the calibration curve with a sensitivity of 26 ng/mL, a practical working range of 46.8-6000 ng/mL parathion.     

Significance of breast carcinoma-associated antigens as a monitor of tumor burden: characterization by monoclonal antibodies

Use of monoclonal antibodies (Mc 3 and Mc 8) prepared against human mammary-epithelial antigens of human mild fat globule membranes has enabled characterization of breast carcinoma (BC) associated antigens (BCAA), antibodies, and circulating immune complexes (CIC). For this study, BC patients were grouped on the basis of measurable tumor burden: Group I patients with no evidence of disease at sampling time; Group II patients with tumor burden less than or equal to 5 g; and Group III patients with known regional or distal metastases. In an in vitro simulation of tumor burden change, selected BC patients' sera were admixed with Mc 3 and Mc 8 at optimal concentration. CIC reduction (dissociation) for Groups I and III and increment (formation) for Group II were noted. Unlike Group I sera, Groups II and III sera required 4- to 16-fold dilution of Mc 3 and 4-fold more concentrated Mc 8 to achieve maximal CIC changes. Serum BCAA isolated by use of both Mc 3 and Mc 8 immunobead procedures showed apparent Mr 33,000 monomer, 66,000 dimer, and 95,000 trimer. When BCAA were added to BC patients' sera, autologous combinations resulted in small (7.7S) CIC for Groups I and III, and medium (9 to 12S) CIC for Group II. Conversely, allogenic combinations resulted in mainly small CIC for Group I, and intermediate CIC for Group II and Group III. Evaluation of circulating BCAA concentration by use of a three-step radioligand technique demonstrated significant discrimination between BC patients' sera (mean = 105 ng/ml) and normal control sera (less than or equal to 20 ng/ml). BCAA were found to be elevated in 31 of 46 (67%) Group I (mean = 70 ng/ml), 41 of 43 (95%) Group II (mean = 197 ng/ml), and 30 of 46 (65%) Group III (mean = 50 ng/ml) patients' sera, as compared to "background" levels in malignant melanoma and normal controls. Benign breast disease sera showed moderate BCAA increases (mean = 48 ng/ml) in 20 of 35 (57%) patients. Furthermore, serial sample determination of BCAA in 36 selected BC patients confirmed the above pattern, indicating that this assay can be used with some restriction to monitor tumor burden. Whereas in early breast carcinoma increase in BCAA concentration was concurrent with or antedated clinical objective evidence of tumor burden increase, significant decreased BCAA concentration was observed with tumor burden reduction. Overall, increased BCAA levels were associated with limited tumor burden (Group II) while decreased BCAA levels were observed with no evidence of disease (Group I) and known regional or distal metastatic advanced disease (Group III) during patients' follow-up.     

Development of monoclonal antibodies directed against cocaine and cocaethylene: potential new tools for immunotherapy

Cocaine abuse is a major health problem, with the number of overdose-related incidents on a constant increase. Monoclonal antibodies against cocaine and its major toxic metabolite cocaethylene, have been developed for immunotherapeutical neutralization in vivo. A series of monoclonal antibodies with high affinity for cocaethylene and cocaine were obtained. Clones DASm244-4D8A4A4 (4D8) and DASm244-5B3C3C6 (5B3) were selected and fully characterized. The antibodies secreted exhibited 1.40 x 10(8) and 3.69 x 10(7) M(-1) affinity constants for [3H]-cocaine and cocaethylene, respectively. In addition to cocaine, they bound to cocaethylene and did not recognize non-toxic cocaine metabolites. They did not bind to blood cells, indicating that they may be potential tools for cocaine neutralization in vivo in cases of overdose.     

Development and characterization of monoclonal antibodies against mouse TSLP

Epithelial-derived thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that is mainly produced by epithelial cells. It has been shown to play a key role in the development of Th2-type allergic inflammation. Commercial antibodies available against TSLP can only be used in Western blot assay, which further limits investigation of its function. Here we efficiently generated a panel of anti-mouse TSLP monoclonal antibodies in rats with DNA priming-protein boosting strategy. Overall, four MAb strains (4B12, 4E11, 5D7, and 6H10) were obtained and their characterizations were identified. The MAbs can specifically bind to TSLP according to the ELISA and FACS assays. It was found that they recognized distinct epitopes. They are useful in detecting TSLP expression in the tissue by immunoblotting and in the cytoplasm by intracellular staining assay. Thus, these antibodies will be valuable tools for studying TSLP biological functions.     

Development of mouse hybridomas for production of monoclonal antibodies specific to Burkholderia mallei and Burkholderia pseudomallei

Burkholderia mallei and B. pseudomallei are designated category B biothreat agents on the "select agents" list established by the NIH and CDC. Development of monoclonal antibodies (MAbs) that could effectively differentiate these two closely related species of bacteria and other non-pathogenic Burkholderia bacteria is urgently needed. Splenocytes from mice immunized with various antigen preparations from either B. mallei (American Type Culture Collection [ATCC] 23344) or B. pseudomallei (ATCC 23343) were used for production of hybridomas. Using a three-step cross-screening protocol, a total of 10 hybridomas were selected that produced MAbs which specifically recognized B. mallei 23344 but did not bind B. pseudomallei, Pseudomonas aeruginasa, or any of the other nine Burkholderia species tested. All 10 MAbs targeted to the lipopolysaccharide (LPS) molecules of B. mallei and reacted strongly with 12 out of 15 different strains of B. mallei tested. A total of 14 hybridomas that produced MAbs reacting with B. pseudomallei 23343, but not with B. mallei, P. aeruginasa, or any other nine non-pathogenic Burkholderia species were also selected. All 14 MAbs appeared to react with a proteinase K-sensitive 200-kDa band by immunoblotting analysis. Surprisingly, these 14 MAbs that were raised against the ATCC 23343 strain failed to react to any of the other 13 different strains of B. pseudomallei examined. In conclusion, our B. mallei-specific MAbs can effectively recognize 80% of the different B. mallei strains tested, and all the B. pseudomallei-specific MAbs appeared to react with a unique antigen present only in the ATCC 23343 strain, but not in any other strains of B. pseudomallei tested.     

Differential induction of N(2),3-ethenoguanine in rat brain and liver after exposure to vinyl chloride

Although vinyl chloride (VC) clearly induces hepatic angiosarcoma in humans and rodents, a causal association with brain tumors has not been definitively established with the available epidemiological and experimental evidence. Because VC acts by genotoxic mechanisms, DNA adduct formation is thought to be a sensitive biomarker of early events in carcinogenesis. Adult male Sprague Dawley rats were exposed to 0 or 1100 ppm VC for 1 or 4 weeks (6 h/day, 5 days/week) by inhalation. Male weanlings were similarly exposed for 5 days. Another group of male adults was exposed to 1100 ppm [(13)C(2)]VC in a nose-only inhalation apparatus for 5 days (6 h/day). A sensitive gas chromatography high-resolution mass spectrometry assay was used to measure the major promutagenic DNA adduct, N(2),3-ethenoguanine (N(2),3-epsilonG), in rat brain and hepatocyte (HEP) DNA. The respective concentrations of N(2),3-epsilonG in control rat brain DNA at 1 and 4 weeks were 5.0 +/- 0.9 and 5.6 +/- 1.1 N(2),3-epsilonG/10(8) unmodified guanine. There was no change in N(2),3-epsilonG in adult rat brain after exposure to 1100 ppm VC for 1 or 4 weeks. In HEPs from the same animals, these adduct concentrations increased from 5.5 +/- 1.4 to 55 +/- 2.0 N(2),3-epsilonG/10(8) unmodified guanine after a 1-week exposure and from 3.0 +/- 0.3 to 110 +/- 20 N(2),3-epsilonG/10(8) unmodified guanine after a 4-week exposure. When weanlings were exposed to 1100 ppm VC for 5 days, there was a statistically significant (P = 0.04) increase in N(2),3-epsilonG in brain from 1.5 +/- 0.2 to 4.4 +/- 1.1 N(2),3-epsilonG/10(8) unmodified guanine. Weanlings exposed to 1100 ppm VC had an even greater increase in N(2),3-epsilonG in HEPs from 1.6 +/- 0.1 to 97 +/- 5.0 N(2),3-epsilonG/10(8) unmodified guanine. [(13)C(2)]N(2),3-epsilonG was not detected in brain DNA from adult rats exposed to 1100 ppm [(13)C(2)]VC for 5 days but was present in HEP DNA at 55 +/- 4.0 [(13)C(2)]N(2),3-epsilonG/10(8) unmodified guanine. The concentrations of the endogenous adduct in both organs were unchanged after this exposure. 7-(Oxoethyl)guanine (OEG), the major DNA adduct formed by VC, was reduced to 7-(2-hydroxyethyl)guanine and measured by liquid chromatography-electrospray ionization-tandom mass spectrometry in brain and HEP DNA from rats exposed to 1100 ppm VC for 1 week. Whereas 4.0 +/- 0.8 OEG/10(6) unmodified guanine were present in HEP DNA from VC-exposed rats, no adducts were detectable in brain DNA (detection limit, 0.3 OEG/10(6) unmodified guanine). These findings indicate that the genotoxic metabolite of VC is not formed in or transported to adult rat brain. Thus, it is unlikely that N(2),3-epsilonG or other VC-induced promutagenic DNA adducts play a significant role in initiating carcinogenesis in adult rat brain after exposure to VC. The data for weanling rats are less clear. Whereas a small increase in N(2),3-epsilonG in the brains of weanlings was found after exposure to 1100 ppm VC, the resulting adduct concentration was similar to that measured in unexposed adults. Future exposures of weanling rats to the stable isotopically labeled compound will be necessary to conclusively determine whether this increase was due to VC.     

Development of a monoclonal antibody-based immunoassay for cyclic DNA adducts resulting from exposure to crotonaldehyde

In order to develop an immunoassay for DNA modifications resulting from exposure to crotonaldehyde, monoclonal antibodies specific for the 8R,6R- and 8S,6S-stereoisomers of 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxy-6 - methylpyrimido[1,2-a]purine-10(3H)one were produced. These cyclic 1,N2-propanodeoxyguanosines are formed in DNA exposed to crotonaldehyde in vitro. Three of the four antibodies were most specific for one stereoisomer while the fourth was most specific for the other stereoisomer. Fifty % inhibition of binding in an enzyme-linked immunoabsorbent assay using two of these antibodies and capable of detecting 0.5 mumol of 1,N2-propanodeoxyguanosine per mol of deoxyguanosine was developed. The method was validated by comparison to results obtained with fluorescence assay.     

Development and characterization of murine monoclonal antibodies specific for dissimilatoric copper nitrite reductase

Several hybridoma cell lines from mice were established, producing monoclonal antibodies (MAbs) directed against the dissimilatoric copper nitrite reductase (dNIR) to detect actual denitrifying bacteria at the single cell level under nondestructive conditions in the environment. The mice were immunized with native or recombinant enzyme gained from two different bacteria, Ochrobactrum anthropi and Alcaligenes faecalis. The antibodies obtained could be divided into two groups according to their different specificities for dNIRs of different bacteria: One group of MAbs had a broad specificity for dissimilatoric copper nitrite reductases from bacteria of different phylogenetic taxa; the other group gave only a clear signal with the corresponding immunogen. None of the raised MAbs showed a cross reactivity with the dissimilatoric heme nitrite reductase. One MAb from each group (MAb dNIR1a and MAb dNIR29) has been selected for further investigation. Data of enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunofluorescence-microscopy are presented and compared with phylogenetic data. Furthermore, results of Western blotting experiments with cells, grown without nitrate under aerobic conditions, and cells cultivated with nitrate under anaerobiosis, are shown.     

1,N6-etheno-2' -deoxyadenosine and 3,N4-etheno-2'-deoxycytidine detected by monoclonal antibodies in lung and liver DNA of rats exposed to vinyl chloride

1,N⁶-Etheno-2'-deoxyadenosine (dAdo) and 3,N⁴-Etheno-2'-deoxycytidine(dCyd) are formed in vitro by reaction of DNA with the electrophilicmetabolites of vinyl chloride (VC), chloroethylene oxide andchloroacetaldehyde. To detect and quantitate these DNA adductsin vivo, we have raised a series of specific monoclonal antibodies(Mab). Among those, Mab EM-A-1 and Mab EM-C-1, respectively,were used for detection of dAdo and dCyd by competitive radioimmunoassay(RIA), following pre-separation of the etheno adducts from DNAhydrolysates by high perfonnance liquid chromatography. At 50%inhibition of tracer-antibody binding, both Mab had a detectionlimit of 187 fmol and antibody affinity constants (K) of 2 x10⁹ l/mol. The levels of dAdo and dyd were quantitated in theDNA of lung and liver tissue of young Sprague-Dawley rats exposedto 2000 p.p.m. of VC for 10 days. The dAdo/2'-deoxyadenosineand dCyd/2'-deoxycytidine molar ratios were 1.3 x 10^–7and 3.3 x 10^–7 respectively, in lung DNA, and 5.0 x 10^–8and 1.6 x 10^–7 in liver DNA. When hydrolysates of 3 mgof DNA were analyzed by RIA at 25% inhibition of tracer-antibodybinding, dAdo and dCyd were not detected in liver DNA from untreatedrats above the limiting dAdo/2'-deoxyadenosine and dCyd/2'-deoxycytidinemolar ratios of 2.2 x 10^–8 and 3.1 x 10^–8, respectively.     

Preparation and characterization of monoclonal antibodies to thrombomodulin

Thrombomodulin (TM) is an endothelial cell surface molecule, capable of specific binding for thrombin. The thrombin/TM complex promotes activation of plasma anticoagulant protein C (PC) and negatively regulates blood coagulation. Along with anticoagulant function, TM has been shown to have additional physiological functions such as regulation of fibrinolysis, cell adhesion, tumor growth, and embryonic development. The extracellular region of TM contains a lectin domain and six epidermal growth factor (EGF)-like domains, which are required for the various functions. To analyze the functions, we established a panel of monoclonal antibodies (MAbs) reactive to each functional domain. We obtained MAbs that react to the lectin domain or the front half of EGF domains from the first to the third using the antigen of a transfected cell line expressing full-length TM. We also obtained MAbs that reacted to the bottom half of the EGF domain from the fourth to the sixth using the antigen of a transfected cell line expressing truncated form of TM lacking the lectin domain and the EGF domains from the first to the third. All obtained MAbs could be used for Western blotting. Endothelial cell function for PC activation can be mimicked by transfected cells positive for TM and the endothelial cell protein C receptor (EPCR). Effects of the established MAbs on thrombin-dependent PC activation on the transfected cells were examined. Strong inhibition was demonstrated by three MAbs, which reacted to the fourth or fifth EGF domain, but not by MAbs to the other domains. The fourth EGF domain is known as the interaction site for PC, and the fifth domain is known to be required for thrombin binding. The sixth EGF domain also has been shown to be required for thrombin binding. An MAb against the domain strongly inhibited thrombin-binding. However, the MAb demonstrated little effect on thrombin dependent PC activation. The contradictory results demonstrated with the MAb to the sixth EGF domain suggest an unknown molecular mechanism for PC activation on the cell surface. A panel of MAbs reactive to each domain could be useful for analyzing the multifunctional molecule thrombomodulin.     

Cutaneous adverse reactions to therapeutic monoclonal antibodies for cancer

Advances in molecular biology have led to the successful development of targeted monoclonal antibodies to several types of malignancies. By June 2007, nine therapeutic monoclonal antibodies had been approved by the US Food and Drug Administration to treat various human cancers. In general, the adverse reactions of these agents have been milder than their cytotoxic chemotherapy counterparts, but side effects do occur. Cutaneous adverse reactions to the first of these agents were rare, and primarily limited to infusion reactions, local inflammation at injection sites, and ill-defined transient eruptions. However, the use of monoclonal antibody therapy against the epidermal growth factor receptor-1 in gastrointestinal and head and neck cancer has been frequently associated with significant skin reactions. As the use of these agents becomes more widespread, the recognition and management of these skin reactions becomes an increasingly important part of patient care.     

Unsuitability of monoclonal antibodies to oncogene proteins for anti-tumour drug-targeting

Monoclonal antibodies (MAbs) to ras, sis, erb-B, src, myb and myc oncoproteins were evaluated for their potential to target anti-cancer drugs to malignant cells. Each antibody was tested for reactivity against both fixed and viable cultured human tumour cells by immunofluorescence, and all reacted against a variety of fixed tumour cell preparations. Reactions were also observed against fixed non-malignant cells. None, however, reacted significantly with viable cells. Two antibodies (against ras and myc proteins) were tested for their ability to localize to tumour xenografts in nude mice, and conjugates were constructed by linking these antibodies to methotrexate using human serum albumin as an intermediate carrier. Neither antibody localized to tumour in vivo, and the methotrexate conjugates were not significantly cytotoxic for tumour cells in vitro, in contrast to similar conjugates simultaneously prepared with a proven anti-tumour MAb (791T/36). It was concluded that currently available MAbs to oncogene proteins are not suitable vectors for targeting cytotoxic agents to tumour cells.     

Immunotherapy for non-Hodgkin's lymphoma: monoclonal antibodies and vaccines.

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.     

Development of monoclonal antibodies to the human breast carcinoma cell line PMC42

In an attempt to identify antigens expressed during breast differentiation, three murine monoclonal antibodies, CIBr2, CIBr7, and CIBr18, were produced against the human pleomorphic breast carcinoma cell line PMC42. All three monoclonal antibodies reacted with previously undescribed antigenic determinants on the PMC42 cell line. Antibody CIBr18 reacted only with the immunizing cell line PMC42, whereas antibodies CIBr2 and CIBr7 showed minimal reactivity toward a panel of 34 human leukemia- and solid tumor-derived cell lines. The antigenic determinants detected by the three antibodies were distinct, and each showed variable expression in PMC42 monolayer and organoid cultures. The heterogeneity of staining seen on PMC42 cultures may reflect the fact that this cell line contains up to eight morphologically distinct cell types. Antigen expression correlated with cell type in some instances, whereas in other instances phenotypic subdivision within a cell type was apparent. Antigens recognized by antibodies CIBr7 and CIBr18 were characterized biochemically. In Western blotting, antibody CIBr7 identified a single band of an apparent molecular weight of 38,000 within PMC42 cell lysates. Sodium dodecyl sulfate-polyacrylamide gel analysis of polypeptides immunoprecipitated by antibody CIBr18 from [35S]methionine-labeled PMC42 cell lysates identified two glycoproteins of apparent molecular weights of 115,000 and 120,000, respectively. No biochemical data for the CIBr2 antigen are yet available. All three antigens were detected in human mammary epithelium and some non-breast tissues. The expression of these antigens in normal and neoplastic mammary epithelia is discussed in terms of antigen heterogeneity and changes in antigen expression upon conversion to the malignant state.     

Murine monoclonal antibodies to human pancreatic cancer: specificity and sensitivity

Pancreatic carcinoma (n = 7), pancreatitis tissue (n = 4), normal pancreas tissue (n = 5), colonic adenocarcinoma (n = 4) and in vitro human pancreatic cancer cell lines (n = 6) were studied with the murine monoclonal antibodies (MAbs) 3DS2A, AR1-28, AR2-20, Ca19-9 and CA17-1A to determine their immunohistologic specificity and sensitivity for use as radiolabeled diagnostic imaging agents. Using the avidinbiotin-immunoperoxidase staining technique, MAbs 3DS2A and AR1-28 stained 86 and 100% of pancreatic cancer specimens, respectively. MAbs 3DS2A and AR1-28 are suitable agents for use as radiolabeled diagnostic imaging agents in patients with pancreatic cancer.