Osteosarcoma of the head and neck: meta-analysis of the nonrandomized studies.
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Head and Neck Neoplasms↗
Biomedical subjects
G B Snow
Publications and source records attributed to G B Snow.
[Surgery of the cervical lymphatic system. I].
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Carcinoma, Squamous Cell↗
The size of lymph nodes in the neck on sonograms as a radiologic criterion for metastasis: how reliable is it?
PURPOSE: A definition of cut-off points for nodal size is essential to determine whether cervical lymph nodes are metastatic or not. Because the currently used size criteria are defined for random populations of patients with head and neck cancer, we set out to study whether these criteria are optimal for patients without palpable metastases in different levels of the neck We defined optimal size criteria for sonography by calculating the sensitivity and specificity of different size cut-off points. METHODS: We compared the sensitivity and specificity of different size cut-off points as measured on sonograms for various levels in the neck in a series of 117 patients with and 131 patients without palpable neck metastases. RESULTS: A minimum axial diameter of 7 mm for level II and 6 mm for the rest of the neck revealed the optimal compromise between sensitivity and specificity in necks without palpable metastases. For all necks together (with and without palpable metastases), the criteria were 1 to 2 mm larger. CONCLUSION: Our findings indicate that the current sonographic size criteria used for random patient populations are not optimal for necks without palpable metastases, nor can the same cut-off points be used for all levels in the neck.
Evaluation Studies as Topic↗
Exfoliated oral cell messenger RNA: suitability for biomarker studies.
The efficacy of chemoprevention trials can be improved by the use of biomarkers of carcinogenesis that serve as surrogate end points. The aim of this study was to assess the perspectives of using mRNA isolated from oral exfoliated cells for biomarker research in chemoprevention of upper aerodigestive tract cancer. When using reverse transcription-PCR in combination with Southern blotting and hybridization, it was possible to detect transcripts from only five cells. With the quantitative RNase protection assay, we could only detect highly abundant transcripts. The integrity of the RNA was verified by Northern blotting, which showed a variable degree of degradation, depending on the gene studied. Interestingly, although specific transcripts were found to be intact to a certain extent, the rRNA appeared to be completely degraded, suggesting that a specific protein synthesis shut-off mechanism exists in terminally differentiated oral epithelial cells. Altogether, this differential RNA degradation makes accurate measurement of transcript levels of most genes, as determined in exfoliated oral cells, unreliable. Because this RNA degradation process is likely to start before the cells are shed from the tissue, the results of measurements of transcript levels in biopsies of oral tissue should be interpreted with caution.
Adult↗
Is selective neck dissection really as efficacious as modified radical neck dissection for elective treatment of the clinically negative neck in patients with squamous cell carcinoma of the upper respiratory and digestive tracts?
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Carcinoma, Squamous Cell↗
High dose rhenium-186-labeling of monoclonal antibodies for clinical application: pitfalls and solutions.
BACKGROUND: Rhenium-186 (186Re) has ideal properties for adjuvant radioimmunotherapy (RIT). However, the lack of suitable methods for high dose 186Re labeling of monoclonal antibodies (MAbs) has hampered the use of 186Re in clinical RIT. After development of a chemically identical multistep procedure for the production of 186Re-MAG3-MAb and 99mTc/99Tc-MAG3-MAb conjugates for use as a matched pair, the authors now report on further progress to make this labeling method broadly applicable for high dose 186Re labeling. METHODS: The number of metal-MAG3 groups that can be coupled to a MAb without alteration of the biodistribution was investigated by radioimmunoscintigraphy (RIS) in patients with head and neck squamous cell carcinoma (HNSCC). For labeling with 500 mCi [186Re]ReO4-, an efficient chemoprotection was introduced to suppress the damaging effects of radiation during conjugation and conjugate purification. Furthermore, the authors developed strategies that make the procedure easy and safe to perform at any medical center. RESULTS: MAbs showed a minor variation in biodistribution in HNSCC patients when the number of metal-chelate groups per MAb varied between < 1 and 4.3. High dose 186Re-MAb conjugates (150-250 mCi) with a Re-MAG3:MAb ratio of 3.4 were obtained with a radiochemical purity of > 95% and minimal aggregate formation (< or = 6%). Furthermore, a semiautomated labeling device and a convenient 100 mCi labeling kit in the form of a dried 186Re-MAG3-TFP ester were developed. RIT studies in HNSCC-bearing nude mice showed that high dose 186Re-labeled MAb U36 is more effective than iodine-131-labeled MAb U36. CONCLUSIONS: High dose 186Re-MAb conjugates were prepared that exhibit an optimal stability, immunoreactivity, and pharmacokinetic behavior. The availability of a kit procedure for coupling 186Re to MAbs might open the possibility of a broad application of 186Re in RIT.
Animals↗
A gain of novel tissue specificity in the human Ly-6 gene E48.
The Ly-6 Ag family consists of glycosyl-phosphatidylinositol-anchored surface proteins with a molecular mass of about 15 kDa. Seven members of the murine family have been characterized, and from five of these the genes have been cloned. Three members of the human family have been characterized: CD59, Ag E48, and the RIG-E or TSA-1/Sca-2 Ag. Most of the genes are expressed on lymphocytes, but some are expressed on other tissues as well. The mapped genes of the murine Ly-6 Ags, as well as of CD59, were shown to have a highly conserved structure, each consisting of four exons. The human E48 Ag was originally identified as a target Ag for radioimmunotherapy of patients with squamous cell carcinoma. The Ag is expressed on keratinocytes, but evidently not on lymphocytes. Molecular cloning of the cDNA encoding the Ag revealed that this Ag is most likely the human homologue of the murine Ly-6 Ag, ThB. In this paper, we describe that, in contrast to all other Ly-6 genes, the gene encoding the human E48 Ag consists of only three exons. Sequences at the 5' end of the transcription start site were shown to drive keratinocyte-associated expression. These data suggest that the functional elimination of an ancestral Ly-6 exon 1 switched the expression from lymphocytes toward keratinocytes.
Animals↗
Assessment of malnutrition parameters in head and neck cancer and their relation to postoperative complications.
BACKGROUND: Malnutrition is reported frequently in head and neck cancer patients. The impact of malnutrition on surgical outcome is not clearly understood. The purpose of this study was to define the usefulness of six different parameters in scoring malnutrition and to determine the nutritional parameter primarily related to postoperative complications. METHODS: Sixty-four patients undergoing major surgery for advanced head and neck cancer were studied prospectively, and six different parameters were used to define malnutrition. Logistic regression was used to relate nutritional parameters to postoperative complications. RESULTS: The parameters applied all identified different aspects of the nutritional status, as malnutrition varied between 20% and 67%. Logistic regression analysis identified a weight loss of more than 10% to be the most prominent predictive parameter for the occurrence of major postoperative complications. CONCLUSIONS: Patients with weight loss more than 10% during the six months before surgery are at a great risk for the occurrence of major postoperative complications.
Carcinoma, Squamous Cell↗
The surgical management of recurrent or residual pleomorphic adenomas of the parotid gland. Analysis and results in 40 patients.
From 1974 to 1995, 40 patients were treated surgically at the University Hospital Vrije, Universiteit Amsterdam for recurrent or residual pleomorphic adenomas of the parotid gland after previous surgery. The median interval between the initial procedure and surgery for the recurrence was 122 months. Eleven patients had one or more attempts to resect tumor recurrences prior to referral. During reoperation at this institution it was decided to refrain from tumor resection in three patients. Tumor control in two of these patients was achieved using radiotherapy. In the third patient a "wait-and-see" policy was adopted. The other 37 patients underwent en bloc surgical excisions of their tumor and/or previously incised tissues. Among the 36 patients operated for histopathologically benign disease, 16 received postoperative radiotherapy (to 6500 cGy). None developed a further recurrence, the median follow-up being 106 months. Only one of these patients experienced permanent segmental facial nerve paralysis. Malignant transformation of tumor occurred in two patients. One of these patients died of locoregional disease after surgery and radiotherapy. Radical tumor resection was deferred in the other patient, with tumor control achieved using radiotherapy (7000 cGy). However, since recurrent disease tends to be multifocal in origin, prolonged routine follow-up is required.
Adenoma, Pleomorphic↗
Rapid elimination of mouse/human chimeric monoclonal antibodies in nude mice.
At our laboratory we are currently evaluating the suitability of mouse/human chimeric monoclonal antibodies (cmAb) for use in radioimmunotherapy of patients with head and neck squamous cell carcinoma (HNSCC). We have developed cmAb containing the human constant IgG1 domain and the variable domains of murine mAb (mmAb) E48 and U36 respectively. We considered the tumour-bearing nude mouse to be a well-validated model for a first testing of the targeting capabilities of these cmAb in comparison with the mmAb. Therefore, 3 microg cmAb E48 (labelled with (125)I) and 3 microg mmAb E48 (labelled with (131)I) were simultaneously injected into HNSCC-bearing nude mice and, at various assay times, mAb uptake in blood and other tissues was assessed. Remarkably, while in roughly 50% of the animals the biodistribution of the conjugates was similar, in the other animals cmAb E48 showed a much higher blood clearance than mmAb E48. This resulted in a lower tumour uptake of cmAb E48 in comparison with mmAb E48. To determine whether this phenomenon was related to mAb E48 or to the animal model, other cmAb-mmAb combinations were evaluated in the same way: cmAbs SF-25, 17-1A and U36 (all IgG1) were tested and all showed a rapid elimination in about 50% of the animals. Besides a decrease in blood concentration, an increase of cmAb levels in liver and spleen was observed within 24 h after injection. Isotype-specific enzyme-linked immunosorbent assays showed that mice that demonstrated a rapid elimination of cmAb from the blood had much lower endogenous IgGI, IgG2b and IgG3 titres than mice showing normal clearance. IgG2a levels were low in all mice. Biodistribution experiments with 3 microg chimeric 17-1A isoforms showed high blood clearance in a proportion of the mice for IgG1, IgG3 and IgG4, but not for IgG2. Increase of the cmAb dose to 100 microg resulted in a similar cmAb and mmAb biodistribution in all mice. Moreover, the biodistribution of the F(ab')2 fragment of an IgG1 cmAb was similar for all mice in contrast to that of coinjected whole IgG. On the basis of these results it can be hypothesized that, in mice with low endogenous IgG titres, cmAb with specific isotypes are rapidly removed from the blood (and ultimately from the body) by mediation of Fc-binding receptors. Apparently, in mice with high endogenous IgG titres or in mice receiving a high cmAb dose, these receptors are saturated. Furthermore, the rapid elimination of cmAb from nude mice, which may occur after injection at a low dose, is a phenomenon related to the nude mouse model.
Animals↗
Sequence variation in the monoclonal-antibody-U36-defined CD44v6 epitope.
Monoclonal antibody (mAb) U36 was developed for the treatment of minimal residual disease of head and neck squamous cell carcinoma (HNSCC). The mAb-U36-defined antigen was characterized by cDNA cloning, and was shown to be identical to the keratinocyte-specific CD44 splice variant epican. The epitope recognized by mAb U36 was shown to be located in the v6 domain. Two amino acids within the epitope appeared to differ from the sequences that have been described in literature. The sequence of the epitope appeared to contain glutamic acid at position 367 and lysine at position 374, while valine and arginine respectively have been described before. Interestingly, another anti-CD44v6 antibody with possible clinical application, VFF18, recognizes an epitope in the same area. With respect to the applicability of these antibodies for tumor targeting, this variation might have an influence on antibody-antigen interaction and mAb accumulation in the tumor. Furthermore, this observation raised the question whether the different epitopes are related to the malignant behavior of tumor cells. In this paper we determine the relative affinity of mAb U36 for the variant epitope sequences by tumor cell binding assays using synthetic peptides for competition. The presence of glutamic acid instead of valine at position 367 caused strong competition. Further evaluation showed that the published valine variant does not exist in vivo, and is the result of a sequencing artefact. The effect of substitution of lysine for arginine at position 374 had no effect on the binding of mAb U36 to the cells. This amino acid variation was shown to be due to allelic polymorphism. There was no trend towards allelic imbalance in tumor cells as compared to normal cells.
Amino Acid Sequence↗
Oral squamous cell carcinoma as a second primary malignancy in a patient with previously diagnosed osteosarcoma of the femur.
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Adult↗
Messages from completed randomized trials in head and neck cancer.
During the last three decades numerous randomized trials have been conducted in head and neck squamous cell carcinoma. The issue of pre- vs post-operative radiotherapy in advanced cancers was settled in the late 70s in favour of the latter approach and new fractionation schemes are currently being investigated, with no definite answers as yet. There is no uniform policy regarding the problem of elective neck dissection in early stage anterior oral cavity carcinoma. Often some chemotherapeutic regimen is involved in clinical trials in an attempt to improve on the standard of surgery and radiotherapy. Neoadjuvant chemotherapy has never been proven to benefit patients with advanced squamous cell carcinoma of the head and neck despite being able to decrease the rate of distant metastases. Chemotherapy given prior to or simultaneously with definite radiotherapy seems to offer the best chances for preserving vital organs, such as the larynx. Methotrexate is still the least toxic and most potent drug in recurrent or metastatic disease. The chemoprotective effect of low-dose isotretinoin on multiple primaries in the head and neck has yet to be evaluated.
Carcinoma, Squamous Cell↗
Prospects for future studies in head and neck cancer.
Present therapy of head and neck cancer patients includes surgical procedures, radiotherapy and sometimes chemotherapy. Over recent decades no dramatic improvements have been obtained with these treatment modalities with respect to efficacy and associated morbidity. Of patients with early stage disease (stage I and II), about 25% cannot be cured, while for patients with advanced disease (stage III and IV) this percentage may be as high as 70%. However, owing to advances in our knowledge of molecular biology, immunology, (bio)chemistry and biology of head and neck squamous cell carcinoma (HNSCC), new perspectives on therapy are arising. After several years of optimization several new therapeutic approaches are leaving their infancy and are being evaluated in clinical trials with HNSCC patients. Among other approaches, photodynamic therapy, gene therapy and antibody-based therapy are attracting most attention. The basic concepts and the potential applications of these treatment modalities in the management of head and neck cancer are discussed in this paper.
Antibodies, Monoclonal↗
Prevalence of Epstein-Barr virus in oral squamous cell carcinomas, premalignant lesions and normal mucosa--a study using the polymerase chain reaction.
Epstein-Barr virus (EBV) prevalence was assessed in 12 clinically normal oral mucosas, nine premalignant lesions, 36 oral squamous cell carcinomas (OSCCs) and a human papillomavirus (HPV) 16 positive cell line, derived from an OSCC studied. The polymerase chain reaction (PCR) with two pairs of primers with different sensitivities was used. With primers specific for the BamHIW repeat, EBV was found in 100% of OSCCs, in 77.8% of premalignant lesions and in 8.3% of clinically normal oral mucosas (P = 0.0001). Using primers specific for the single copy BNLF-1 gene, EBV was detected in 50% of OSCC and in none of the premalignant lesions. No statistically significant associations could be established among EBV presence and clinico-pathological data of OSCC. The cell line derived from an HPV/EBV-positive carcinoma did not reveal EBV DNA. The higher prevalence of EBV in OSCCs and premalignant lesions may be due to increased EBV shedding, possibly due to associated immunodepression in these patients, rather than its clonal presence in the neoplastic cells.
Adult↗
All-trans retinoic acid induced gene expression and growth inhibition in head and neck cancer cell lines.
Retinoids are natural and synthetic analogues of vitamin A and have proven activity in various types of cancer. As for head and neck squamous cell cancer (HNSCC), retinoids are especially active in leukoplakia and in preventing second primary cancers. The aim of this study was to assess the growth inhibiting activity of all-trans retinoic acid (all-trans RA) in a panel of six head and neck squamous cell cancer cell lines and to correlate this response to the mRNA expression of factors related to differentiation and receptor mediated signal transduction. Three lines showed minimal, two moderate and one strong growth inhibition after 72 h exposure to all-trans RA. Three lines with a dissimilar response were selected for further studies, the measurement of mRNA expression by northern blotting. It was found that neither the expression nor the induction of retinoic acid receptor (RAR)-alpha and -gamma and retinoic X receptor-alpha mRNA war related to sensitivity. The mRNA expression of RAR-beta was too low to be measured in the three cell lines. The most sensitive cell line was, however, the only one that expressed mRNA of squamous differentiation markers. These data suggest a relationship between the retinoid sensitivity profile and the degree of cellular differentiation.
Carcinoma, Squamous Cell↗
Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients.
Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 +/- 0.3 and 11.1 +/- 0.2 mg (n = 5) or 51.1 +/- 0.1 and 51.0 +/- 0.4 mg (n = 5) of both mE48 IgG and mU36 IgG labelled with 131I and 125I simultaneously and underwent surgery 7-8 days after injection. The mean uptake of iodine-labelled mE48 IgG and mU36 was highest in tumour tissue, 8.9 +/- 8.9 and 8.2 +/- 4.4 %ID kg(-1) respectively. Tumour to non-tumour ratios for oral mucosa, skin, muscle, blood and bone marrow aspirate were 2.5, 5.5, 25.2, 4.7 and 4.0 respectively in the case of mE48 IgG and 2.3, 4.1, 21.0, 5.8 and 5.8 respectively in the case of mU36 IgG. The distribution of mMAbs E48 and U36 throughout tumours that had been collected in previous studies was heterogeneous when administered at a dose of 1 or 12 mg, and homogeneous when administered at a dose of 52 mg. Administration of mE48 IgG (1-52 mg) resulted in a human anti-mouse antibody response in 12 out of 28 patients, while for mU36 IgG (1-52 mg), this figure was three out of 18 patients. cMAb E48 was shown to be highly effective in mediating antibody-dependent cellular cytotoxicity in vitro, while cMAb U36 and mMAbs E48 and U36 were not effective at all. Rationales are provided that give priority to the start of adjuvant radioimmunotherapy trials with 186Re-labelled cMAb U36 IgG in head and neck cancer patients who are at high risk for the development of locoregional recurrences and distant metastases.
Animals↗
Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head and neck squamous cell carcinoma cell lines.
Retinoids can reverse potentially premalignant lesions and prevent second primary tumours in patients with head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been reported that acquired resistance to all-trans retinoic acid (RA) in leukaemia is associated with decreased plasma peak levels, probably the result of enhanced retinoid metabolism. The aim of this study was to investigate the metabolism of retinoids and relate this to growth inhibition in HNSCC. Three HNSCC cell lines were selected on the basis of a large variation in the all-trans RA-induced growth inhibition. Cells were exposed to 9.5 nM (radioactive) for 4 and 24 h, and to 1 and 10 microM (nonradioactive) all-trans RA for 4, 24, 48 and 72 h, and medium and cells were analysed for retinoid metabolites. At all concentrations studied, the amount of growth inhibition was proportional to the extent at which all-trans-, 13- and 9-cis RA disappeared from the medium as well as from the cells. This turnover process coincided with the formation of a group of as yet unidentified polar retinoid metabolites. The level of mRNA of cellular RA-binding protein II (CRABP-II), involved in retinoid homeostasis, was inversely proportional to growth inhibition. These findings indicate that for HNSCC retinoid metabolism may be associated with growth inhibition.
Antineoplastic Agents↗