Biomedical subjects

T E Carey

Publications and source records attributed to T E Carey.

At least 19 recordsLinked to original sources

PubMed1999

Predictive markers for response to chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.

OBJECTIVE: A systematic retrospective study of the largest randomized trial of induction chemotherapy and radiation for advanced laryngeal cancer was undertaken to determine whether specific tumor or biologic factors were predictive of chemotherapy response, organ preservation, or survival. METHODS: The variables analyzed included clinical and histologic factors, immunohistochemical expression of proliferating cell nuclear antigen and p53, and adjusted DNA index measurements. Variables were evaluated for correlation with outcomes of tumor response, organ preservation, and survival. RESULTS: Multivariate analysis revealed that the best predictor of complete response to induction chemotherapy was low T class. The full multivariate model for predicting larynx preservation in patients treated with induction chemotherapy plus radiation shows that T class, p53 overexpression, and elevated proliferating cell nuclear antigen index were independent predictors of successful organ preservation. CONCLUSIONS: These predictive markers should be included in future clinical trials of advanced laryngeal cancer to determine their usefulness prospectively.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

KHRI-3 monoclonal antibody-induced damage to the inner ear: antibody staining of nascent scars.

Intracochlear infusion of the KHRI-3 monoclonal antibody results in in vivo binding to guinea pig inner ear supporting cells, loss of hair cells and hearing loss. To further characterize the basis for KHRI-3-induced hearing loss, antibody was produced in a bioreactor in serum-free medium, affinity purified, and compared to conventionally prepared antibody by infusion into the scala tympani using mini-osmotic pumps. In vivo antibody binding was observed in 10 of 11 guinea pigs. A previously unreported pattern of KHRI-3 antibody binding to cells involved in scar formation was noted in five guinea pigs. All but one of the KHRI-3-infused animals demonstrated a hearing loss of > 10 dB in the treated ear. In five of 11 animals the threshold shift was 30 dB or more, and all had hair cell losses. In one guinea pig infused with 2 mg/ml of antibody, the organ of Corti was absent in the basal turn of the infused ear. This ear had a 45-50 dB threshold shift but, curiously, no detectable antibody binding in the residual organ of Corti. Organ of Corti tissue was fragile in antibody-infused ears. Breaks within the outer hair cell region occurred in 5/11 infused ears. The contralateral ears were normal except for one noise-exposed animal that demonstrated hair cell loss in the uninfused ear. Three animals were exposed to 6 kHz noise (108 dB) for 30 min on day 7. Antibody access to the organ of Corti may be increased in animals exposed to noise, since the strongest in vivo binding was observed in noise-exposed animals. Loss of integrity of the organ of Corti seems to be the primary mechanism of inner ear damage by KHRI-3 antibody. The binding of KHRI-3 antibody in new scars suggests a role of the antigen in scar formation. Antibodies with binding properties similar to KHRI-3 have been detected in 51% of patients diagnosed with autoimmune sensorineural hearing loss; thus, it seems likely that such autoantibodies also may have pathologic effects resulting in hearing loss in humans.

Animals↗

PubMed1999

Expression of major histocompatibility complex antigens in squamous cell carcinomas of the head and neck: effects of interferon gene transfer.

The effect of retroviral-mediated interferon-gamma (IFN-gamma) gene transfer on major histocompatibility complex (MHC) class I and II antigen expression was investigated in 13 head and neck squamous carcinoma cell lines. Six cell lines exhibited increased MHC class I expression, and 10 exhibited increased MHC class II expression after IFN-gamma gene transfer. Differences in MHC antigen expression between parental and transduced cell lines were significant (P = 0. 002) only for cell lines that upregulated MHC class II expression. After incubation in medium containing 100 U/mL recombinant IFN-gamma, or in medium from IFN-gamma retrovirus-transduced NIH 3T3 cells, 12 cell lines significantly upregulated MHC class I expression, and 9 significantly upregulated MHC class II expression. Only cell lines that exhibited increased MHC class II expression after retroviral transduction also upregulated class II expression with exogenous IFN-gamma treatment. Thus some head and neck squamous carcinoma cell lines can upregulate MHC class I and II expression after exogenous application of either IFN-gamma or IFN-gamma retroviral transduction. These are promising findings for head and neck cancer immunotherapy and gene therapy.

Adult↗

PubMed1999

High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas.

Respiratory papillomas (RPs) are benign, virally induced tumors of the larynx and respiratory epithelium that may obstruct the airway and tend to recur frequently. RPs are thought to be the result of infection with the human papillomaviruses (HPVs) types 6 and 11. We surveyed archival RP specimens to determine whether there were correlations of HPV type with patient characteristics or clinical course. Paraffin-embedded papilloma specimens of 45 different patients were analyzed. We assessed HPV types using the polymerase chain reaction with E6 consensus primers, hybrid capture assays (high or low risk), and dot blot hybridization of generic E6 PCR products with E6 type-specific oligonucleotide probes. The presence and type of HPV were correlated with patient data from a retrospective chart review. We found that RPs may have either low- or high-risk HPV types and some contain multiple HPV types. Respiratory infection with high-risk HPV apparently introduces a long-term risk of squamous cell carcinoma development, even in the absence of conventional cofactors. Low-risk HPV infection may also act in association with these cofactors to promote carcinogenesis. Our data also show a racial imbalance in RP that may indicate a difference in genetic resistance and/or susceptibility to HPV infection and the development of RP.

Adolescent↗

PubMed1999

Chromosomal aberrations identified in culture of squamous carcinomas are confirmed by fluorescence in situ hybridisation.

AIMS: Chromosomal aberrations in tumour cells are often not discernable by direct analysis. Although cell culture allows qualitative analysis of the karyotype, potential selection and evolution during growth in vitro may yield misleading data. To determine whether aberrations observed in vitro are representative of the original lesion, chromosomal aberrations found after prolonged growth in vitro of two squamous cell carcinomas of the head and neck (SSCHN) were evaluated with fluorescence in situ hybridisation (FISH) on the original tumour nuclei. METHODS: Specific karyotypic aberrations identified in cultures of two squamous cell carcinomas were targets for FISH analysis on tumour sections. Chromosome painting mixtures were selected based on in vitro karyotypic data. FISH was performed on cultured interphase and metaphase cells, and on histological sections from the original tumours. RESULTS: The 9cen and 17cen probes yielded FISH signals consistent with the aneusomies predicted for the respective chromosomes from the culture karyotypes. Whole chromosome 9 paint confirmed the prior existence in the tumours of i(9p) and i(9q), although only the latter hybridised with the 9cen probe. FISH data also supported in vivo representation of the diploid and tetraploid tumour subclones observed in cultures. In tumour HFH-SCC-8a, FISH results were generally concordant between cultured interphase and metaphase cells and the histological sections, and improved the interpretation of marker chromosomes identified in culture. CONCLUSION: The karyotypes obtained in these cases after prolonged passage in culture were consistent with the genetic alterations in the original tumours.

Carcinoma, Squamous Cell↗

PubMed1998

Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck.

Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long-arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two-year survival compared to those without 18q LOH (30% vs. 63%; P = 0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC.

Carcinoma, Squamous Cell↗

PubMed1998

The induction of P450-mediated oxidation of all-trans retinoic acid by retinoids in head and neck squamous cell carcinoma cell lines.

All-trans retinoic acid (RA) can be catabolized into polar metabolites by cytochrome P450 (P450) in several tissues including the skin. We examined eight different squamous cell carcinoma (SCC) cell lines to determine their capacity to induce P450-mediated oxidation of RA. Among the eight different cell lines, enhanced catabolism was detected in AMC-HN-1, -2, -5, and -6, whereas it was not found in the cell lines of AMC-HN-3, -4, -7, and -8. It was found that the enhanced catabolism brought on by P450 induction was blocked when RA was added to AMC-HN-6 along with actinomycin D or cyclohexamide. Also, this catabolism was inhibited by ketoconazole. P450-mediated oxidation was detectable within 4 hours of RA treatment, and RA catabolism reached its maximum 16 hours after treatment. P450 was induced by 13-cis-RA, 9-cis-RA, and retinal; however, retinol could not induce P450. In conclusion, P450 can be induced by retinoids in head and neck SCC (HNSCC) cells and the ability of retinoids to induce P450 can serve as an important factor in determining the biological effect of retinoids.

Antibiotics, Antineoplastic↗

PubMed1998

The HPV 6 E6/E7 transforming genes are expressed in inverted papilloma.

A role for human papilloma virus (HPV) infection in the pathogenesis of head and neck neoplasms has gained support in recent years. Expression of two early-region HPV genes, E6 and E7, is widely accepted as essential for viral-induced carcinomas of the genital tract. These oncoproteins interact with the products of the cellular tumor suppressor genes, p53 and retinoblastoma, and inactivate them. Examining E6/E7 transforming gene expression is an important step toward elucidating the pathogenesis of HPV in head and neck neoplasms. We introduce nasal inverted papilloma (IP) as a novel system for evaluating viral genomic expression and transforming gene regulation of tumorigenesis by virtue of its association to HPV infection and potential for malignant progression. We describe here a reverse transcriptase-polymerase chain reaction approach for the detection of HPV E6/E7-specific transcripts in RNA extracted from IR. A primer pair flanking previously mapped HPV 6 E6/E7 splice donor/acceptor sites was used to direct amplification of cDNA. Reverse transcriptase-polymerase chain reaction experiments generated products representing the 1.2 Kb E1E4 splice transcript and a smaller unclassified fragment in IP from two patients. These results provide evidence for HPV 6 E6/E7 expression in IP with the potential to encode transforming proteins.

DNA, Viral↗

PubMed1998

Expression of human papillomavirus 6 in inverted papilloma arising in a renal transplant recipient.

A 36-year-old renal transplant recipient taking cyclosporin A presented with bilateral nasal polypoid lesions involving the nasal septum and lateral nasal walls. Pathologic findings from surgical excision demonstrated inverted papilloma (IP) with focal atypia and mild dysplasia. DNA extracted from the tissue was tested with the polymerase chain reaction (PCR) using human papillomavirus (HPV) E6 and L1 consensus primers. This revealed amplification of the expected size fragment consistent with the presence of HPV DNA. Hybridization of PCR products with HPV type-specific oligonucleotide probes revealed a strong signal with only HPV 6. This result was confirmed by PCR amplification with HPV 6 type-specific primers. RNA extracted from the tissue was subjected to reverse transcription PCR (RT-PCR) with a primer pair specific for viral E6/E7 transcripts. The HPV early proteins, E6 and E7, are the transforming proteins implicated as critical for tumorigenesis. RT-PCR experiments generated products representing the E1/E4 spliced transcript originating from the E6/E6 promoter and a smaller unclassified fragment. These results provide evidence for HPV 6 E6/E7 expression in IP, lending credence to the concept that HPV may play a role in the origin of this neoplasm. Histologically normal nasal tissue from the same patient contained HPV DNA and similar transcripts to those described in the IP specimen.

Adult↗

PubMed1997

Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen.

Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL). Sera from patients with rapidly progressive hearing loss have been shown to contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using guinea pig inner-ear tissue as the antigenic substrate and either Western blot or immunofluorescence (IF) or both, we tested sera from 74 patients suspected to have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73 (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF stained supporting cells with a staining pattern like that previously observed with the KHRI-3 monoclonal antibody. There was concordance between Western blot and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were positive in Western blot were also positive by IF, three were negative by both tests, and two each were positive by one assay but negative by the other. Absorption of patient sera with human inner-ear tissue removed antibody reactivity to the guinea pig supporting cells, indicating that the antigen detected by the autoantibody is also present in the human inner ear. Absorption with an equal volume of white or red blood cells from the tissue donor did not remove the antibody reactivity to inner ear, showing that the absorption by inner-ear tissue is specific. Sera from three patients positive in both assays also stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal antibody, indicating that the monoclonal and human antibodies recognize the same antigen. The results support the hypothesis that patients with autoimmune sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell antigen that is phylogenetically conserved and defined by the murine monoclonal antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the inner ear, it is likely that autoantibodies with the same antigenic target are also pathogenic in humans.

Animals↗

PubMed1997

Evidence that loss of chromosome 18q is associated with tumor progression.

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -17B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were examined for loss of heterozygosity (LOH) on chromosome 18q. Metastatic or recurrent cell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastatic (14C) tumors, lost all of 18q. However, in the other three cases, there was a partial loss of 18q in the recurrent or metastatic tumor cell lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss of 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and neck, including the tumor tissue corresponding to UM-SCC-81B. Three of the additional seven tumors and cell lines had 18q LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, there was complete concordance between allelic loss in the tumor and allelic loss in the corresponding cell line. The common region of loss established by tumors and cell lines with partial loss includes 18q21-18qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which are both components in a transforming growth factor-beta-like signaling pathway. Loss of 18q in metastatic and locally recurrent tumors, but not in primary tumors from the same patients, suggests that a tumor suppressor gene in this region may be important in the progression of squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed1997

Human squamous carcinoma cell invasion in organ-cultured skin.

In a previous study we showed that normal human epidermal keratinocytes were capable of invading the dermis of organ cultured skin when the tissue was treated with an exogenous source of epithelial growth factors (Fligiel and Varani (1993) Invasion Metastasis, 13, 225-233). Here we examined human squamous carcinoma cells from three different tumors for ability to invade the dermis in the same model. Invasion occurred in 40-80% of the tissues, depending on the tumor line, and was observed with equal frequency under both growth factor-free conditions and in the presence of exogenous growth factors. These data demonstrate that malignant human epithelial cells have the capacity to invade the dermis of organ-cultured skin. Unlike normal keratinocytes, there appears to be no exogenous growth factor requirement for invasion by the malignant cells.

Carcinoma, Squamous Cell↗

PubMed1997

Beta 4 integrin transfection of UM-UC-2 (human bladder carcinoma) cells: stable expression of a spontaneous cytoplasmic truncation mutant with rapid loss of clones expressing intact beta 4.

The alpha 6 beta 4 integrin is a component of the hemidesmosome, the anchoring structure in the basal membrane of epithelial cells. alpha 6 beta 4 expression is frequently altered in neoplastic cells. It is sometimes lost and sometimes overexpressed, which suggests that disruption of normal function is involved in neoplastic transformation. To examine the effect of this integrin on the growth and behavior of malignant cells that have lost beta 4, we transfected a full-length beta 4 cDNA into the UM-UC-2 cell line that expresses alpha 6 but not beta 4. Although large numbers of clones were obtained when a control vector was used in the transfection, only 12 clones could be isolated that expressed beta 4. Of these, only two beta 4-positive clones, clones 8 and 11, persisted long enough for further study. Clone 8 cells initially expressed beta 4, but within 2 weeks, all positive cells were lost from the culture. Clone 11 persisted in culture and retained strong surface expression of alpha 6 beta 4. Biochemical analysis and Western blotting revealed that this clone contained a truncated form of beta 4 that had lost the distal cytoplasmic domain. We conclude that expression of wild-type beta 4 in UM-UC-2 inhibits cell growth, presumably by an integrin-mediated signaling pathway. Clone 11 escaped from normal signaling because the cytoplasmic domain, a region essential for basal polar localization, was lost. The alpha 6 beta 4 integrin appears to have tumor suppressor activity in epithelial tumors.

Antigens, CD↗

PubMed1997

p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department of Veterans Affairs Laryngeal Cancer Cooperative Study Group.

OBJECTIVE: To determine the relationship of p53 mutations in advanced laryngeal carcinomas to p53 immunohistochemistry, organ preservation, and patient survival. DESIGN: Paraffin-embedded tumor specimens were obtained from patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multi-institutional randomized clinical trial comparing induction chemotherapy (cisplatin and fluorouracil) plus radiation therapy surgery plus postoperative radiation therapy. Tumor specimens were analyzed for p53 mutations in exons 5 through 8 by using single-strand conformational polymorphism (SSCP) analysis followed by DNA sequencing of all variants. Five-year follow-up data were available for all patients studied. SUBJECTS: Forty-four patients enrolled in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study from whom paraffin-embedded tumor specimens were readily available. RESULTS: p53 immunostaining did not correlate with p53 SSCP and DNA sequencing results. More than half (62% [16/26]) of the tumors that overexpressed p53 immunohistochemically did not have a detectable p53 gene mutation. Similarly, 39% (7/18) of tumors that did not overexpress p53 did have a p53 gene mutation. p53 mutations were present in 39% of tumors tested. Mutations within exon 5 made up 41% of p53 gene mutations in laryngeal carcinomas. Transitions were the most common type of mutation in this study (92% of mutations). CONCLUSIONS: The presence of a p53 mutation as detected by SSCP is associated with decreased patient survival. Further study is required to confirm this relationship and to determine whether specific p53 mutations predict organ preservation.

Carcinoma, Squamous Cell↗

PubMed1997

Frequent loss of heterozygosity on chromosome arm 18q in squamous cell carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23.

OBJECTIVES: To determine the frequency and regions of loss on chromosome arm 18q in uncultured head and neck squamous cell carcinomas. DESIGN: Polymerase chain reaction amplification of DNA extracted from 18 tumor specimens (1 patient had 2 tumors) and blood samples from 17 patients with head and neck squamous cell carcinoma was performed using primers flanking 16 microsatellite repeat polymorphisms spanning most of chromosome 18q. DNA was extracted only from specimens with greater than 70% tumor nuclei. SETTING: Research university. PATIENTS: Seventeen individuals with newly diagnosed head and neck cancer. MAIN OUTCOME MEASURE: Loss of heterozygosity (LOH). RESULTS: There was LOH at more than 1 locus in 52% (9/ 17) of the tumors; 3 tumors had LOH at all informative markers. Four had loss at only 1 locus, raising the total with loss to 12 (75%) of 16. Loss of 18q11.1-q12.3 in 4 tumors without distal loss defines a proximal region of loss. Loss of heterozygosity affecting 18q21.1 in 1 tumor, without proximal loss and LOH for 18q21.1, 18q22, or 18q23 in 9 (52%) of 17 tumors defines a distal region of loss. CONCLUSIONS: Loss of heterozygosity on chromosome arm 18q is not an artifact of in vitro culture. The finding of 18q LOH in 50% to 70% tumors makes 18q an important region for study. Regions 18q11.1-q12.3 and 18q21.1-q23 are common regions of loss, indicating that there may be more than one 18q tumor suppressor gene involved in the genesis and progression of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗

PubMed1997

In vivo binding and hearing loss after intracochlear infusion of KHRI-3 antibody.

The IgG1 mouse monoclonal antibody (MAb) KHRI-3, binds to an antigen of 65-68 kDa expressed on inner ear supporting cells in guinea pigs. We previously showed [Nair et al. (1995) Monoclonal antibody induced hearing loss. Hear. Res. 83, 101-113] that mice carrying the KHRI-3 hybridoma develop high frequency hearing loss and loss of hair cells in the basal turn suggesting that this MAb causes immune-mediated sensorineural hearing loss. To evaluate the specificity of this effect, sterile KHRI-3 and control IgG1 preparations were infused directly into the guinea pig cochlea using Alzet mini-osmotic pumps. Assessments included: (1) hearing, measured by click auditory brain stem responses (ABRs); (2) in vivo antibody binding; and (3) the structural integrity of the organ of Corti. Nine animals were infused with KHRI-3 preparations and 5 controls were infused with control IgG1. Four guinea pigs given KHRI-3 developed 25-55 dB hearing loss. Control animals showed no difference from baseline. In vivo binding of KHRI-3 was detected in the organ of Corti in 6 of the 9 animals, including all 4 that had hearing loss. No staining was observed with control antibody. Confocal microscopy revealed that the in vivo KHRI-3 antibody binding pattern was identical to that obtained by incubating fixed tissue in vitro with KHRI-3. Histologic examination revealed an increased frequency of hair cell loss in KHRI-3 treated ears when compared to either the contralateral ears of the same guinea pigs or the IgG1 treated ears of control animals. The lesions in the infused ears of guinea pigs were scattered throughout the cochlea from base to apex. These experiments demonstrate the following points: (1) Antibodies can be chronically infused directly into the cochlea of living animals. (2) The KHRI-3 antibody binds to live supporting cells within the organ of Corti. (3) Infusion of an inner ear specific antibody affects auditory function. (4) The infusion of irrelevant antibody had no effect on the structure or function of the ear. This system provides an animal model for further studies of antibody-induced sensorineural hearing loss.

Animals↗

PubMed1997

Establishment and characterization of nine new head and neck cancer cell lines.

We established new cell lines from head and neck cancer patients for studies of adhesion molecules and cellular behavior in nine patients with primary or metastatic cancer treated at the Asan Medical Center. Explant cultures of fresh tumor tissue were used to develop new permanent tumor cell lines. Lines were tested for tumor formation and histology in nude mice. Flow cytometry and indirect immunofluorescence were used to assess DNA content and expression of the alpha 6, beta 4, and beta 1 integrin subunits and the intercellular adhesion molecule 1 (ICAM-1). In vitro growth patterns and adhesion to plastic were assessed using phase contrast microscopy. AMC-HN-1 to -8 were derived from patients with squamous cell carcinoma. AMC-HN-9 was from an undifferentiated carcinoma of the parotid gland. The 8 lines we tested produced nude mouse tumors that are identical to the histology of the original tumors. AMC-HN-1, -2, -5, and -9 have epithelioid or spindle cell morphology with poor cell-to-cell and cell-to-substrate adhesiveness. AMC-HN-3, -4, -7, and -8 grow as adherent epithelioid monolayers. AMC-HN-6 exhibits multilayer stratification. Four lines are near diploid, 4 are hyperdiploid and 1 is hypodiploid. Only three express ICAM-1. All lines express the alpha 6, beta 4, and beta 1 integrin subunits but to different extent. Four, AMC-HN-1, -2, -5, and -6, express the beta 4 integrin at low levels, AMC-HN-3, -4, -7, and -9, have intermediate beta 4 expression, and AMC-HN-8 has extremely high beta 4 expression. The AMC-HN cell lines are representative in vitro models for the study of head and neck cancer biology. Our preliminary results indicate a close relationship between integrin expression and cell adhesion in vitro.

Adult↗

PubMed1997

Identifying genetic changes associated with tumor progression in squamous cell carcinoma.

Tumor behavior is the result of specific genetic changes that alter gene expression. From our cytogenetic studies chromosome 18 loss emerged as a common genetic change in squamous carcinoma cell lines. In this report we summarize data that link loss of 18 to tumor progression and reduced survival, indicating that one or more tumor suppressor gene(s) are located on this chromosome. Tumors grown in vitro were karyotyped either as short-term or permanent cultures. Loss of chromosome 18 was measured by karyotype, decreased frequency of heterozygosity at the DCC locus, and loss of heterozygosity (LOH) for microsatellite repeat polymorphisms (MSRP). Loss of any part of chromosome 18 was observed in approximately 63% of cultured tumors. Primary and secondary tumors from the same individuals sometimes differed in loss of 18 indicating that this genetic change is associated with tumor progression. Heterozygosity for DCC was present in only 3/19 cultured SCC (16%), compared with 68% (11/16) of blood samples from unrelated donors, which is consistent with LOH in roughly one half of the cases. Of 4 informative cases with normal and tumor tissue, LOH was observed in 2. Microsatellite analysis also shows loss of 18q in 55% of fresh tumors. Analysis of tumor tissue and cell lines from the same patient gave identical results. There was an excess of deaths from cancer in the group with 18 loss (20/25) when compared with the group without (5/15). Loss of chromosome 18 appears to be a marker of tumor progression in SCC. It is likely that mutation affecting DCC or another gene on 18 affects tumor growth or spread, leading to more rapid progression and reduced survival.

Carcinoma, Squamous Cell↗