NCCN practice guidelines for head and neck cancer. National Comprehensive Cancer Network.
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Head and Neck Neoplasms↗
Biomedical subjects
J Ridge
Publications and source records attributed to J Ridge.
Effects of gamma-IFN and NGF on subpopulations in a human neuroblastoma cell line: flow cytometric and morphological analysis.
Neuroblastomas are neural crest-derived tumors that contain neuronal, melanocyte, and Schwann cell precursors. We examined the effects of treatment with gamma-interferon (gamma-IFN) and nerve growth factor (NGF), alone, and in combination, on these progenitor subpopulations in the human neuroblastoma cell line, SH-SY5Y. Using fluorescence-activated flow cytometry (FACS), changes in expression of three differentiation-specific or -associated marker proteins, the 200 kD neurofilament protein, the myelin basic protein, and the S-100 protein, were analyzed. Growth rates and morphological changes associated with each treatment over the 2-wk incubation period were noted. The greatest effects were observed with combined IFN + NGF treatment. These were significant increases in expression of all three proteins, distinctive morphological signs of differentiation, and extensive inhibition of proliferation compared to control cultures. Treatment with NGF alone resulted in increased neurofilament protein expression and in the length and number of neurite extensions, but there was no effect on the growth rate. IFN induced striking morphological changes, significant inhibition of growth, and changes in protein expression that correlated with neuronal to non-neuronal subpopulation shifts due to the death of differentiated cells. When treatment was discontinued after 15 d, the morphological changes induced by NGF were reversed within 2-3 d, while those induced by IFN +/- NGF were present up to 4 wk post-treatment. Small, neuroblastic colonies were observed throughout the treatment period and within 4-6 wk after the cessation of treatment this cell-type fully reconstituted the cultures suggesting the presence of a stem cell. Our results indicate that treatment with gamma-IFN +/- NGF can regulate growth and induce, either stem cells or progenitor neuronal, Schwann and melanocyte subpopulations in the SH-SY5Y cell line to irreversibly differentiate.
Cell Division↗
Consistent selection of mutations in the 5'-untranslated region of oral poliovirus vaccine upon passaging in vitro.
We have previously found that upon passaging type 3 oral poliovirus vaccine (OPV) in cell cultures the proportion of revertants at nucleotide 472 rapidly increases [Chumakov et al.: Proceedings of the National Academy of Sciences of the United States of America 88:199-203 1991]. Systematic study on the accumulation of these revertants showed that it was dependent on the multiplicity of infection and the temperature at which virus was grown. Revertants at position 472 of type 3 OPV accumulated faster in vaccines derived from Sabin Original (SO) substrain than from RNA-plaque purified (RSO) substrain. The rate of accumulation of 472-C revertants differed among cell lines and was higher in overgrown cell cultures suggesting that host factors are involved in the selection of mutants. We also found that accumulation of mutants occurred in vitro at position 480 in type 1 and position 481 in type 2 OPV, making the selection for revertants in domain F of the 5'-noncoding region a general phenomenon for all three Sabin strains. Assessment of the abundance of these mutants may be used for evaluation of the quality of OPV lots.
Base Sequence↗
Traumatic medial displacement of Rotalok uncemented acetabular component. A case report.
The failure of uncemented acetabular components has been described in association with component wear, disassembly, and proximal migration. The authors report a case of medial displacement following minor trauma some 18 months after surgery. The component involved differs in design from both press-fit, porous-coated or screw-in, fully threaded acetabular cups. The authors suggest that additional screws should be inserted to enhance long-term stability.
Accidental Falls↗
Assessment of the viral RNA sequence heterogeneity for control of OPV neurovirulence.
By using sensitive mutant analysis by PCR and restriction enzyme cleavage we have found that among several positions that differ between the wild-type and attenuated type 3 poliovirus genomes, only two positions, 472 and 2493, showed variability in vaccine lots. Of these two, only position 472 correlates with neurovirulence in monkeys, while the abundance of revertants at position 2493 indicated the type of seed virus and the passage level. Conditions of cell culture influence the rate of mutant selection, suggesting that some cellular factor(s) may be involved in selection of 472-C. Determination of 472-C content predicts which vaccine lots would fail the monkey neurovirulence test. These results imply that the PCR method can be used for optimization of manufacturing conditions.
Animals↗
Dynamics of differentiation in human epidermoid squamous carcinoma cells (A431) with continuous, long-term gamma-IFN treatment.
We investigated the long-term effects of continuous gamma interferon (gamma-IFN) treatment on A431, a human squamous carcinoma cell line. Cells were grown in an in vitro culture system, which over time produces cohesive cell masses ("tumoroids") exhibiting three-dimensional, histotypically differentiated structures, e.g., keratin "pearls", intercellular bridges (desmosomes), elongated flattened cells (squames) and stratification. The effects of gamma-IFN on cell growth, morphology and stage of differentiation were assessed at different treatment times by light and electron microscopy and by immunohistochemical staining using antibodies to keratins 1 and 14 and to filaggrin, markers of specific stages of keratinocyte differentiation. Our results show that A431 cells have the capacity for spontaneous differentiation, that this capacity is significantly enhanced and accelerated by gamma-IFN treatment leading to terminal differentiation and extensive cell death by 2 wk. Despite continuous exposure to IFN, a small number of viable, undifferentiated cells remain. Their proliferation, evident by 3 wk, reconstitutes the tumoroid which once again contains the full range of differentiating cell types.
Biomarkers, Tumor↗
Propagation and properties of Kaposi's sarcoma-derived cell lines obtained from patients with AIDS: similarity of cultured cells to smooth muscle cells.
Cells derived from Kaposi's sarcoma (KS) were propagated in vitro using conditions which resulted in elimination of contaminating fibroblasts and the emergence of homogeneous cell populations which morphologically resembled smooth muscle cells and had neoplastic characteristics. In long-term culture, they differentiated into large ribbon-like cells with longitudinal fibrillarity of their cytoplasm. These fibrils stained red by Masson trichrome staining, and were reactive with antibodies to desmin. Dense bodies typical of myoblasts were observed in some cells by electron microscopy. The cells did not form capillary structures like endothelial cells, they lacked Weible-Palade bodies, and did not express the blood-clotting Factor VIII-related antigen or receptors for the lectin Ulex europaeus agglutinin I. They did express four other antigens, however, in common with endothelial cells. The cells did not form tumors in athymic nude mice; however, they formed colonies in soft agar, manifested tumor-like growth on muscle organ cultures, and were invasive in an artificial basement membrane invasion assay. The results indicate that a component of KS is closely related to leiomyoblasts and and has neoplastic properties.
Acquired Immunodeficiency Syndrome↗
Pharmacokinetic studies of mouse monoclonal antibodies to a rat colon carcinoma: I. Comparison of biodistribution in normal rats, syngeneic tumor-bearing rats, or tumor-bearing nude mice.
The pharmacokinetics of two iodine-131-(131I) labeled murine anti-rat colon carcinoma monoclonal antibodies (D3 and E4) were compared in normal Sprague Dawley rats, syngeneic BDIX rats, or nude mice bearing that tumor. Results of antibody uptake after i.v. administration were analyzed in terms of accumulation and localization indices for normal tissues and tumor. Statistically significant differences between rat and mouse tissue biodistribution were found. D3, which reacts in vitro with the tumor and several normal rat tissues, cleared quickly from the blood of rats and was specifically targeted to several normal tissues, notably the lung. Virtually no targeting to the tumor was observed. Nude mice, however, showed a slower blood clearance and specific antibody targeting only in the tumor. Similar results were seen after injection of another antibody, E4, which is tumor-specific in vitro. Data suggest that studies on the xenogeneic nude mouse model may not necessarily be relevant to the choice of monoclonal antibodies for clinical diagnostic imaging or therapy.
Adenocarcinoma↗
Monoclonal antibodies to a rat colon carcinoma: model for monoclonal antibody therapy of solid tumors.
Tumor progression, lung metastasis, and death occur in tumor-bearing BD IX syngeneic rats in a fashion similar to the course of patients with metastatic colon cancer. In an effort to establish a relevant model for monoclonal antibody (MoAb) therapy of tumors, we generated murine MoAb against DHD/TR, a dimethylhydrazine-induced rat colon carcinoma which has been adapted to cell culture. Murine MoAb 17B10 E4 (E4) reacts with the TR tumor and shows weak immunoperoxidase reactivity with normal rat tissues. Murine MoAb 5F7 D3 (D3) reacts with the tumor and a variety of normal rat epithelia. Both are IgG2a and mediate cytotoxicity by rat peripheral blood mononuclear cells. 18D5 F6 (F6) also reacts with the tumor and normal tissues but is an IgG2b and does not mediate cytotoxicity in the presence of rat effector cells. Iodinated E4 and D3 antibodies retained their immunoreactivity. E4 revealed 9.8 x 10(5) antigenic sites per TR cell, with an affinity constant of 9.35 x 10(7) M-1, while D3 demonstrated 2.5 x 10(6) antigenic sites and an affinity constant of 4.2 x 10(7) M-1. Immunoblotting showed that the antigens recognized by D3 and E4 are glycoproteins with molecular weights of 27,000 and 66,000, respectively. F6 failed to react with its antigen present in the blot. This rat colon carcinoma and the monoclonal antibodies described here may provide experimental data useful for implementing monoclonal antibodies in cancer therapy.
Animals↗
Interferon-gamma induces altered oncogene expression and terminal differentiation in A431 cells.
In tumor cell lines in which oncogene expression is abnormal, modulation of the expression of the oncogene (myc, src, or ras) by interferons (IFNs) has been observed concurrently with cell growth inhibition or phenotypic reversion. Oncogene expression has also been reported to vary during the differentiation of several neoplastic cell lines. Treatment of monolayer cultures of A431, a human epidermoid carcinoma cell line, with IFN-gamma resulted in rapid morphological alterations and cell death not seen with either IFN-alpha or IFN-beta. These changes were accompanied by elevated expression of mRNA's for p21 (the c-ras gene product) and the epidermal growth factor receptor as well as increases in the biosynthetic rate of their respective proteins. These effects likewise appeared to be specific for IFN-gamma. Growth inhibition by IFN-gamma was also observed when A431 cells were grown in a three dimensional in vitro culture system. Immunohistochemical staining of these "tumoroids" with a differentiation specific, anti-keratin antibody indicated that IFN-gamma enhanced expression of this keratin. This observation suggests that the killing by IFN-gamma of A431 cells may result from an acceleration of terminal differentiation.
Animals↗
The use of flow cytometry and cell sorting in a human colon carcinoma model.
We investigated the growth characteristics of a human colon carcinoma cell line, WiDr, grown in culture flasks and on chick embryonic skin (CES). WiDr cells labeled in vitro with bromodeoxyuridine (BrdU) and analyzed by combined propidium iodide/Hoechst 33258 fluorescence showed evidence of more BrdU incorporation in early S phase as compared to late S phase. When inoculated on the CES, WiDr cells multiplied and invaded the underlying skin. Morphologic examination showed that with extended culture WiDr cells on the CES undergo progressive structural organization with the development of acini and basal lamina, structures similar to those in in vivo tumors. WiDr cells were labeled with monoclonal antibody to carcinoembryonic antigen (CEA) and the brightest 2% of the population was sorted. When subsequently grown on the CES, the sorted cells formed significantly more acinar structures at 3 and 6 days of culture than an unsorted population grown for a comparable time.
Animals↗
Influence of spatial configuration of carcinoma cell populations on the expression of a tumor-associated glycoprotein.
Monoclonal antibody B72.3 was generated using a membrane-enriched fraction of cells from a mammary carcinoma metastasis and has been shown previously to have a high degree of selective reactivity for human breast and colon carcinoma versus normal adult tissues. The reactive antigen has been shown to be a high-molecular-weight glycoprotein complex of approximately 220,000 to 400,000 and is termed tumor-associated glycoprotein 72 (TAG-72). We report here a dichotomy in the expression of TAG-72 in carcinoma biopsy material versus carcinoma cell lines. While 44% (25 of 56) of human breast carcinoma and 80% (16 of 20) of colon carcinoma biopsies express TAG-72 as assayed by radioimmunoassay or immunohistochemistry, only one of 25 breast cancer cell lines [MCF-7 (one variant)] and one of 18 colon cancer cell lines (LS-174T) express this antigen. Furthermore, TAG-72 expression in these two cell lines was shown to be a property of a low percentage of cells within each culture. Attempts to enhance TAG-72 expression in LS-174T cells by propagation on extracellular matrix proteins, such as collagen, laminin, and fibronectin, or in serum-containing or serum-free, hormone-supplemented medium proved unsuccessful. A pronounced increase in TAG-72 expression was observed, however, when the LS-174T cells were grown under culture conditions which promote three-dimensional growth. LS-174T cells grown in spheroid or suspension cultures demonstrated a 2- to 7-fold increase in TAG-72 antigen expression, while those grown on agar plugs demonstrated a 10-fold increase. When the LS-174T cell line was injected into athymic mice to generate tumors, the level of TAG-72 antigen increased over 100-fold, to levels comparable to those seen in the metastatic tumor masses from patients. Thus, spatial configuration of carcinoma cell populations is shown to influence the expression of a tumor-associated antigen and the subsequent surface binding of monoclonal antibody B72.3. The implications of these findings in the potential utility of monoclonal antibodies for the in vivo detection and destruction of carcinoma masses are discussed.
Antibodies, Monoclonal↗