Variety Of Different Tumors Research Articles

The Role of Ets Factors in Tumor Angiogenesis

Angiogenesis is a critical component of tumor growth. A number of growth factors, including VEGF, FGF, and HGF, have been implicated as angiogenic growth factors that promote tumor angiogenesis in different types of cancer. Ets-1 is the prototypic member of the Ets transcription factor family. Ets-1 is known to be a downstream mediator of angiogenic growth factors. Expression of Ets-1 in a variety of different tumors is associated with increased angiogenesis. A role for other selected members of the Ets transcription factor family has also been shown to be important for the development of tumor angiogenesis. Because Ets factors also express a number of other important genes involved in cell growth, they contribute not only to tumor growth, but to disease progression. Targeting Ets factors in mouse tumor models through the use of dominant-negative Ets proteins or membrane permeable peptides directed at competitively inhibiting the DNA binding domain has now demonstrated the therapeutic potential of inhibiting selected Ets transcription factors to limit tumor growth and disease progression.

Unexpected 99mTc-tetrofosmin findings during myocardial perfusion scintigraphy: intraindividual comparison with PET/computed tomography

99mTc-tetrofosmin single photon emission computed tomography (SPECT) is routinely used in the evaluation of coronary artery disease. A variety of different tumors, however, also demonstrate 99mTc-tetrofosmin uptake. We report six patients found with unexpected mediastinal and thoracic tumor uptake during Tc-tetrofosmin myocardial perfusion scintigraphy (MPS). We investigated 2,155 patients with Tc-tetrofosmin MPS during 2006-2007. One thousand four hundred and eighty-six of these patients had no coronary history and were sent to our department due to newly developed thoracic complaint such as chest pain, dyspnea and others. Six hundred and sixty-nine patients had coronary history. All patients underwent 99mTc-tetrofosmin exercise study. Patients with unexpected extracardiac Tc-tetrofosmin findings during MPS were referred to PET/CT for further diagnostic investigation. Region of interest (ROI; 99mTc-tetrofosmin) and SUVmax (2-[F]fluoro-2-deoxy-D-glucose, F-FDG) were estimated and the results were compared with histological findings. Abnormal mediastinal and/or thoracic activities were visualized in six of the 2,155 patients with 99mTc-tetrofosmin images. Subsequently, the patients underwent resection of a thymoma (n=2), nonsmall cell lung cancer (n=1) and breast cancer (n=3). In the patients with breast cancer one was a male patient with ductal, invasive breast cancer. Benign thymomas showed high 99mTc-tetrofosmin ROI >4.0 and low F-FDG SUVmax <2.0, whereas low 99mTc-tetrofosmin ROI <2.0 were found in nonsmall cell lung cancer and breast cancer and high F-FDG SUVmax >2.5 in these malignant tumors. During Tc-tetrofosmin SPECT exercise stress tests performed in patients with suspected coronary artery disease, much more attention must be given to unexpected extracardiac uptakes. With 99mTc-tetrofosmin a large variety of different unknown tumors can be detected during MPS.

Expression of MAGE-A12 in Oral Squamous Cell Carcinoma

Melanoma associated-A antigens (MAGE-A) are silent in normal tissues except testis. However, they are activated in a variety of different tumors. Thus, their expression is highly specific to cancer cells. Reverse transcription-nested polymerase chain reaction (RT-nPCR) is a highly sensitive technique that has been used successfully for the detection ofMAGE genes in tissue samples. The aim of the study is to analyze the expression rate of MAGE-A12 in oral squamous cell carcinoma (OSCC) using a high sensitive RT-nPCR. Total of 57 tissue samples obtained from patients with OSCC and 20 normal oral mucosal (NOM) probes of otherwise healthy volunteers were included to this study. No expression of MAGE-A12 was observed in the non-neoplastic NOM tissues. MAGE-A12 was expressed in 49.1% of the investigated tumor samples. The correlation between malignant lesion and MAGE-A12 detection was significant (p < 0.001). It is concluded that results of this study may indicate MAGE-A12 as a useful additional diagnostic marker especially for the early detection of OSCC distinguishing neoplastic transformation and detection of occult and/or rare disseminated cancer cells. In addition, MAGE-A12 expression in OSCC may also determine a new immunotherapeutic target and might be warranted to develop vaccine for OSCC.

In VivoElectroporation for Gene Therapy

PLASMID DNA-BASED GENE TRANSFER is attractive because it eliminates the need for a biological vector, although it has been handicapped by the lack of efficient and/or effective delivery methods. When compared with viral delivery, the advantages include reduced potential for immunogenicity, integration into the genome, and environmental spread. One method that has emerged as a means to facilitate delivery of plasmid DNA is in vivo electroporation or electropermeabilization. Gene therapy-specific descriptions include gene electroinjection, gene electrotransfer, electrically mediated delivery, or electrogene transfer. For the purpose of this minireview, all these terms are referred to as in vivo EP. In vivo EP has also been used to facilitate transdermal delivery, the use of electric pulses to transport molecules through the skin, but this area of research will not be discussed. Electroporation originated for in vitro transfection (Neumann et al., 1982) and over the past 25 years has become a standard laboratory method. The administration of electric fields under specific pulse conditions increases cell membrane permeability, which allows uptake of molecules through the cell membrane. The initial demonstration of in vivo EP was the delivery of chemotherapeutic agents to solid tumors (Okino et al., 1987). In the midto late 1990s, the effectiveness of this approach for drug delivery was demonstrated in a variety of different tumors in animals and humans (Gothelf et al., 2003). This technique was then tested for enhanced plasmid DNA delivery (Heller et al., 1996; Nishi et al., 1996). In vivo EP is applicable to all tissues tested, the primary issue being accessibility. The use of in vivo EP for plasmid DNA delivery has seen tremendous growth, including the initiation of the first clinical trials. Gene expression level and kinetic patterns after in vivo EP delivery can be varied for different applications by manipulation of the electrode configuration, electrical parameters, and tissue of delivery (Table 1). The versatility of expression is a distinct advantage, and these variables should be carefully selected to match the specific gene transfer application. Therapeutic in vivo EP delivery focuses on a variety of applications such as cancer therapy, regulation of protein levels to enhance or reduce function, or the amelioration of symptoms of iatrogenic or natural disease. Vaccine and preventive gene expression has also been demonstrated. Like other gene delivery methods, enhancement of transgene expression by in vivo EP may also be developed for possible economic rather than therapeutic benefit. Examples include the production of monoclonal antibodies (Perez et al., 2004; Tjelle et al., 2004) or the generation of healthier livestock (Prud’homme et al., 2006). Plasmids or oligonucleotides may also be delivered to explore promoter or gene function. Expression of reporter genes may be used to optimize in vivo EP parameters, to explore the mechanism of EP, or simply to demonstrate delivery in a new tissue. The increased use of in vivo EP for gene delivery has established its potential for many therapeutic applications. Numerous published studies and reviews (Heller, 2003; Andre and Mir, 2004; Heller et al., 2005) describe in vivo EP delivery of plasmid DNA. This minireview is limited in scope to the most recent studies using in vivo EP for delivery of plasmid DNA. The focus is on those studies that demonstrated a clear therapeutic response with the potential to be used clinically.

Epstein–Barr virus in breast cancer: artefact or aetiological agent?

The Epstein-Barr virus (EBV) has been reported to be associated with a variety of different tumours; for some of these malignancies, including breast cancer, the association remains controversial. This might be due in part to differences in the methodologies used to detect EBV in tissue samples. One approach favoured by many groups is to use immunohistochemistry to detect an EBV protein, EBNA1, which is essential for the maintenance of viral latency in infected cells and therefore should be a good marker for the presence of the virus. However, in this issue of the Journal of Pathology, Hennard and colleagues report that one of the antibodies frequently employed to detect EBNA1 in tissue samples cross-reacts with the MAGE4 protein, a cancer testis antigen expressed in many cancer types. Their observation suggests that reports documenting an EBV association on the basis of reactivity with this antibody must be considered unreliable. It also re-opens the debate about whether breast cancer is an EBV-associated disease.

CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment

Signals from the microenvironment have a profound influence on the maintenance and/or progression of hematopoietic and epithelial cancers. Mesenchymal or marrow-derived stromal cells, which constitute a large proportion of the non-neoplastic cells within the tumor microenvironment, constitutively secrete the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). CXCL12 secretion by stromal cells attracts cancer cells, acting through its cognate receptor, CXCR4, which is expressed by both hematopoietic and nonhematopoietic tumor cells. CXCR4 promotes tumor progression by direct and indirect mechanisms. First, CXCR4 is essential for metastatic spread to organs where CXCL12 is expressed, and thereby allows tumor cells to access cellular niches, such as the marrow, that favor tumor-cell survival and growth. Second, stromal-derived CXCL12 itself can stimulate survival and growth of neoplastic cells in a paracrine fashion. Third, CXCL12 can promote tumor angiogenesis by attracting endothelial cells to the tumor microenvironment. CXCR4 expression is a prognostic marker in various types of cancer, such as acute myelogenous leukemia or breast carcinoma. Promising results in preclinical tumor models indicate that CXCR4 antagonists may have antitumor activity in patients with various malignancies. Collectively, these observations reveal that CXCR4 is an important molecule involved in the spread and progression of a variety of different tumors. As such, CXCR4 antagonists, although initially developed for treatment of AIDS, actually may become effective agents for the treatment of neoplastic disease.

The 5' Flanking Region of the Rhesus Monkey H3 (DMBT1) Gene Contains Putative Progesterone Response Elements

DMBT1 (deleted in malignant brain tumors) encodes a large scavenger receptor cysteine rich (SRCR) protein with proposed tumor suppressor properties due to its frequent deletion or lack of expression in a variety of different tumors including endometrial cancers. The gene is alternatively spliced to produce a number of related proteins with suspected functions in mucosal inflammation and epithelial regeneration. Expression of DMBT1 has been demonstrated in a wide variety of cell types, mostly of epithelial origin, including tissues of the respiratory system, the alimentary system, brain, and reproductive system. We have previously identified a Rhesus monkey cDNA clone H3 (homologous to human DMBT1) as a progesterone-induced gene in Rhesus monkey endometrium during the secretory phase of the menstrual cycle. As an initial step in understanding the molecular mechanisms of H3 (DMBT1) regulation we have cloned and sequenced 1.5 kb of the 5'-flanking region expected to contain promoter sequences of the Rhesus monkey gene and identified six putative progesterone receptor binding sites in the 5'-upstream region.

Isolation from phage display libraries of lysine-deficient human epidermal growth factor variants for directional conjugation as targeting ligands.

Ligand-targeted anticancer therapeutics represent an opportunity for the selective and efficient delivery of drugs to tumours. The chemical coupling of ligands to drugs or drug carrier systems is, however, often hampered by the presence of multiple reactive groups within the ligand, for example, epsilon-NH(2) groups in lysine side chains. In this paper, we describe the isolation by phage display of human epidermal growth factor (EGF) variants without lysine and a reduced number of arginine residues. The selection on A431 carcinoma cells also revealed that R41 is indispensable for EGF binding activity as all EGF variants contained an arginine residue at this position. One EGF variant (EGFm1) with K28Q, R45S, K48S and R53S mutations was expressed in bacteria and showed an identical binding activity as wild-type EGF. EGFm1 could be labelled with fluorescein isothiocyanate demonstrating the accessibility of the N-terminal amino group for coupling reagents. Furthermore, coupling of EGFm1 to PEGylated liposomes resulted in target cell-specific binding and internalization of the liposomes. These human EGF variants should be advantageous for the generation of anticancer therapeutics targeting the EGF receptor, which is overexpressed by a wide variety of different tumours.

The eye in malignant disease.

The eye and its adnexae (the extraocular muscles, orbit, orbital walls and eyelids) can be involved in malignant disease, either as the primary source of the tumour or as a site of secondary metastatic involvement. Indeed, there is a wide variety of different tumours which are known to affect the eye, this diversity being a consequence of the richness of the ocular tissues present. In addition, disorders of vision or eye movements may be the presenting signs and symptoms of intracranial malignancy.

NAN0PARTICLE GUIDED MISSILES

MANY CANCER DRUGS CURrently in clinical trials act by inhibiting new blood vessel formation, or angiogenesis. Disruption of this process deprives tumors of the blood supply they need to grow. Now, scientists at Scripps Research Institute and Stanford Medical School have added a new weapon to the antiangiogenesis arsenal [ Science , 296 , 2404(2002)]. The team, led by Scripps immunologist David A. Cheresh, directs tiny polymer beads decorated with a small organic ligand specific for the integrin ανβ3 — a cell-surface molecule specific to endothelial cells of growing blood vessels — to the angiogenic blood vessels of tumor-bearing mice. The cationic nanoparticles also carry a deadly weapon: DNA encoding a mutant form of Raf, a protein kinase common to all known angiogenic pathways. The angiogenic endothelial cells take up and express the mutant gene, which disrupts normal Raf function and blocks blood vessel growth. When mice bearing a variety of different tumors ...

Managing the Neurotoxicity of Paclitaxel (Taxol®) and Docetaxel (Taxotere®) with Neurotrophic Factors

Paclitaxel and the related compound docetaxel are diterpine alkaloids (taxoids) that have demonstrated significant efficacy against a variety of different tumors, including carcinomas of the ovary, breast, head and neck, and lung (1–5). Paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia, during a screening program looking for natural antitumor agents sponsored by the National Cancer Institute in 1971 (6). Before 1993, paclitaxel was referred to as taxol. The Bristol-Myers Squibb Company (Princeton, NJ) registered the name Taxol®, and the generic name paclitaxel was approved. Paclitaxel binds to tubulin and promotes microtubule polymerization (7,8). In tissue culture, paclitaxel causes abnormal bundles of microtubules to form throughout the cytoplasm, disrupting normal cell functions such as proliferation (8). Docetaxel has a similar mechanism of action in that it also binds to the β-subunit of tubulin, inducing polymerization, but may be more potent than paclitaxel (9).

Immunoblot Analysis of CD34 Expression in Histologically Diverse Neoplasms

CD34 is a heavily glycosylated transmembrane protein of approximately 110 kd whose function is essentially uncharacterized. First identified in a myeloid leukemia cell line, immunohistological reactivity with anti-CD34 antibodies is also encountered in a histologically diverse subset of nonhematolymphoid neoplasms including angiosarcoma, solitary fibrous tumors, epithelioid sarcomas, spindle cell lipomas, dermatofibrosarcoma protuberans, and myofibroblastomas. Immunohistological reactivity for CD34 in hematopoietic stem cells and endothelial cells has been shown to correspond to the expression of the CD34 protein. With the exception of gastrointestinal stromal tumors, CD34 protein expression has not been investigated in other CD34 immunohistologically reactive nonhematolymphoid neoplasms. We undertook this study to examine whether the observed reactivity for anti-CD34 antibodies in apparently unrelated tumors is due to the expression of the same protein or whether shared epitopes elaborated by other proteins could account for this reactivity. Immunoblot analyses with anti-CD34 antibodies of six different CD34 immunohistologically reactive lesions show the same approximately 110-kd molecular weight protein. In addition, two cases of dermatofibrosarcoma protuberans show double bands at approximately 110 kd. Laser-capture microdissection of CD34 immunohistologically reactive epithelioid sarcoma and nonreactive epidermal cells illustrates that this reactivity is specific to tumor cells. These results show that the observed immunohistological reactivity with anti-CD34 antibodies is due to the expression of the CD34 protein and not to shared epitopes on unrelated proteins.

Proliferation Markers and Their Uses in the Study of Endocrine Tumors.

A growing body of literature supports the view that the proliferative activity (PA) of tumor cells is an important prognostic indicator for a variety of different tumors. We examined the role of PA in diagnosis and prediction or malignancy of endocrine tumors (ETs) of pituitary gland, pancreas, thyroid, parathyroid glands, adrenal glands, paraganglia, gastroenteric tract, and lung. The data in the literature indicate that the assessment of PA is not a diagnostic indicator of malignancy especially at the individual case level, whereas it can be useful for identifying subsets of malignant tumors with different aggressiveness potential, as well as for choosing therapeutic options in metatstatic lesions. We hope that, in the near future, multiparametric approaches including PA markers, cell growth and differentiation factors, and oncogenes will yield valuable information for diagnosis and prognosis of ETs also in individual cases.

Treatment of a human breast cancer xenograft with an adenovirus vector containing an interferon gene results in rapid regression due to viral oncolysis and gene therapy.

Treatment of a human breast cancer cell line (MDA-MB-435) in nude mice with a recombinant adenovirus containing the human interferon (IFN) consensus gene, IFN-con1 (ad5/IFN), resulted in tumor regression in 100% of the animals. Tumor regression occurred when virus was injected either within 24 hr of tumor cell implantation or with established tumors. However, regression of the tumor was also observed in controls in which either the wild-type virus or a recombinant virus containing the luciferase gene was used, although tumor growth was not completely suppressed. Tumor regression was accompanied by a decrease in p53 expression. Two other tumors, the human myelogenous leukemic cell line K562 and the hamster melanoma tumor RPMI 1846, also responded to treatment but only with ad5/IFN. In the case of K562 tumors, there was complete regression of the tumor, and tumors derived from RPMI 1846 showed partial regression. We propose that the complete regression of the breast cancer with the recombinant virus ad5/IFN was the result of two events: viral oncolysis in which tumor cells are being selectively lysed by the replication-competent virus and the enhanced effect of expression of the IFN-con1 gene. K562 and RPMI 1846 tumors regressed only as a result of IFN gene therapy. This was confirmed by in vitro analysis. Our results indicate that a combination of viral oncolysis with a virus of low pathogenicity, itself resistant to the effects of IFN and IFN gene therapy, might be a fruitful approach to the treatment of a variety of different tumors, in particular breast cancers.

Augmenting the immunogenicity of carbohydrate tumor antigens

Antibody responses have identified cell surface carbohydrate antigens as potentially immunogenic cancer antigens in a variety of different tumors, but immunization with whole tumor cells or cell lysates has only occasionally induced immune responses against these antigens. Three approaches to further augmenting their immunogenicity have been explored, mixture with immunological adjuvants, synthesis of more immunogenic derivatives and conjugation to immunogenic proteins. Conjugation to proteins such as KLH plus the use of potent adjuvants such as QS-21 proved most immunogenic. Carbohydrate epitopes on gangliosides (GM2 and GD2), neutral glycolipids (Le v and Globo H) and glycoproteins (Le v, Globo H, TF, sTn and Tn) are of special interest. Each of these antigen has been synthesized and conjugated to KLH. Their use in preclinical or clinical vaccination studies has resulted in increased IgM and IgG antibody responses against tumors expressing these antigens. Phase I–II clinical trials in patients with cancer have been initiated with each to optimize immunogenicity. The GM2 vaccine has progressed to Phase III trials and the sTn vaccine to Phase II trials aimed at determining the impact of vaccination on survival.

Genetics of melanoma.

Melanoma may cluster in families with 'family cancer syndromes' in which there is a predisposition to a variety of different tumours. Other families seem vulnerable to melanoma alone. In the majority of these families, the propensity to melanoma is associated with the presence of abnormal melanocytic naevi, the so-called atypical mole syndrome (AMS) phenotype. However, in a smaller number of families, individuals are susceptible to melanoma but have normal naevi. There appears, therefore, to be clinical (and probably genetic) heterogeneity. Segregation analysis does not support a predisposition by single dominant gene as an explanation for the AMS/melanoma syndrome. To date, a single gene which is clearly important for susceptibility to melanoma has not been identified. Karyotypic studies of melanoma tumours have pointed to chromosomes 1, 6, 7, 9 and 10 as possible sites for melanoma related genes. Loss of heterozygosity studies have suggested that chromosome 9 may carry a tumour suppressor gene important in familial disease, and linkage studies appear to confirm this. It is not yet clear, however, what percentage of familial melanoma is attributable to this gene. A more longstanding suggestion that a gene on chromosome 1 may be important has not been confirmed, but a chromosome/gene may be responsible for susceptibility in a small subset of melanoma families. Even within AMS families, there is a lack of concordance between the AMS phenotype and susceptibility to melanoma. This might be explained either by the effects of modifying genes, or the environment.

Analysis of experimental antiangiogenic therapy

Angiogenesis is a fundamental process by which new blood vessels are formed. Progressive tumor growth necessitates the continuous induction of new capillary blood vessels which converge upon the tumor. Suppression of tumor growth can be accomplished with the use of antiangiogenesis agents. AGM-1470 is a potent angiogenesis inhibitor in vitro and in vivo. In mouse studies, AGM-1470 has suppressed the growth and neovascularization induced by four murine tumors resulting in a 55% to 77% decrease in tumor growth. In these mice significant toxicity did not result from AGM-1470 therapy. AGM-1470 administered systemically to C57BI 6 male mice for 20 to 28 days inhibited the growth of: (1) Lewis lung carcinoma resulting in a T C (treatment/control = mean tumor volume of treated/mean tumor volume of control) of 0.38 ± 0.03 ( P < .001); (2) colon adenocarcinoma 38 resulting in a T C of 0.23 ± 0.02 ( P < .001); and (3) fibrosarcoma 105 resulting in a T C of 0.31 ± 0.05 ( P < .001). To determine if antiangiogenic therapy was equally effective in mice of both sexes and in immunodeficient animals, we tested AGM-1470 in the treatment of fibrosarcoma 105 in both female mice and nude mice. For female mice T C was 0.24 ± 0.06 ( P < .001). For nude mice T C was 0.27 ± 0.06 ( P < .001). These results demonstrate that AGM-1470 suppresses the growth of a variety of different tumors. Furthermore, the antitumor effect of AGM-1470 therapy is independent of the immune system and sex.

Malignant Fibrous Histiocytoma: History, Histology, Histogenesis

At the XVI. International Congress of the International Academy of Pathology (Vienna, 1986), a session was dedicated to the classification of soft tissue tumors. At this occasion a critical review of malignant fibrous histiocytoma (MFH) was presented. A) The history of MFH revealed that this tumor had been known for many years under a variety of names. Moreover, MFH apparently had frequently been misinterpreted as other tumor types, as for instance rhabdomyosarcoma. Today, there is a discrepancy between the high incidence of MFH among soft tissue sarcomas and its underrepresentation in some widely used tumor classifications. B) The histological appearance may be fully developed and typical for MFH. However, it also may be merely compatible with MFH in less typical tumor areas. Regional differences in morphological appearance may be pronounced. Differential diagnosis can be helped by histochemical methods. C) Histochemical methods--among others--also help to shed light on the histogenesis. More recent findings point to MFH, as a tumor of fibroblasts rather than histiocytes with similarities to loose areolar connective tissue. Although MFH-like areas may occur focally within a variety of different tumors, there remains a large group of sarcomas which do not display any signs of further differentiation even after careful work-up. In these cases the application of the term MFH, as it is understood today, appears to be justified.

Production of pituitary protein 7B2 immunoreactivity by endocrine tumors and its possible diagnostic value.

7B2 is a protein originally isolated from pituitary, which has been shown to be present in the central nervous system and in certain peripheral tissues, with very high concentrations in pancreatic islets. Endocrine and nonendocrine tumors from 185 patients were investigated by RIA for the presence of immunoreactive pituitary protein 7B2. The highest mean concentration of 7B2 immunoreactivity was found in insulinomas [452 +/- 174 (+/- SEM) pmol/g wet wt tissue; n = 16], which was significantly higher than the concentration in normal adult pancreatic tissue (28.3 +/- 4.4 pmol/g; n = 7). High concentrations of 7B2 immunoreactivity also were found in other endocrine tumors. The cellular localization of 7B2 was studied in normal pancreas, pancreas with hyperplastic islets, and endocrine tumors. 7B2 immunoreactivity was localized to B-cells in the normal pancreas and to variable proportions of cells in islet cell hyperplasias, B-cell tumors, and pheochromocytomas. Plasma concentrations of 7B2 immunoreactivity also were determined in 255 patients with established diagnoses of endocrine or nonendocrine tumors. The proportion of patients with elevated plasma concentrations (arbitrarily set at more than 4 SD above the mean) were 42 of 72 with pancreatic islet cell tumors, 7 of 11 with midgut carcinoid tumors, and 5 of 13 with medullary carcinomas of the thyroid. Especially high values were found in patients with glucagonomas (14 of 20), vipomas (12 of 13), and pancreatic polypeptide-producing tumors (5 of 6). Thus, 7B2 immunoreactivity is produced by a variety of different tumors and may serve as a tumor marker, especially in patients with certain pancreatic islet tumors.

A monoclonal antibody which detects a cell surface antigen on murine embryonal carcinoma and early mouse embryo stages may recognize a carbohydrate determinant involving α-linked galactose

A rat monoclonal antibody (5D4) apparently specific for murine embryonal carcinoma cells and cells of the pre-implantation embryo is described. It does not react with differentiated cells from a variety of different tumours and tissues of the mouse. Biochemical studies show that the molecules that carry 5D4 antigen are resistant to protease digestion on the cell surface but susceptible to procedures which affect carbohydrate structure. It is likely that this antibody detects a carbohydrate bearing determinant which may include an α-linked galactose residue.