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Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

At least 109 records · Page 6Linked to original sources
PubMed1996

Laryngeal carcinoma after radiation therapy: correlation of abnormal MR imaging signal patterns in laryngeal cartilage with the risk of recurrence.

PURPOSE: To correlate abnormal magnetic resonance (MR) imaging signal patterns in cartilage with the effectiveness of radiation treatment. MATERIALS AND METHODS: Eighty previously untreated patients underwent MR imaging and radiation therapy with a curative intent. Cartilage was considered to have an abnormal signal pattern if it had intermediate signal intensity on T1-weighted spin-echo (SE) MR images and high signal intensity on T2-weighted SE MR images. The minimum follow-up was 2 years. RESULTS: Abnormal MR imaging signal patterns of the thyroid cartilage (P < .001; P < .04) were more ominous than those of other cartilage. Abnormal signal patterns in cartilage of patients with small tumors (< 5 cm3 and especially < 1 cm3) were less significant. Abnormal signal patterns in cartilage combined with a large tumor (> 5 cm3) worsened the prognosis significantly (P < .05). CONCLUSION: Abnormal MR imaging signal patterns in cartilage may not indicate a poor prognosis in every case. Abnormal signal intensity in the thyroid cartilage combined with a tumor volume of > 5 cm3, however, appears to indicate an adverse prognosis with regard to tumor recurrence.

Adult↗
PubMed1996

Monoclonal antibodies labeled with rhenium-186 using the MAG3 chelate: relationship between the number of chelated groups and biodistribution characteristics.

UNLABELLED: Our previous studies on the preparation of 186Re-MAb conjugates for clinical radioimmunotherapy (RIT) were extended with the aim to derive conjugates which have a high Re:MAb molar ratio, are stable in vitro and in vivo, have favorable biodistribution characteristics and can be used together with 99mTc-MAb conjugates as a matched pair in combined radioimmunoscintigraphy/RIT studies. METHODS: Rhenium and 99mTc-conjugates of intact MAb E48 were prepared according to our previously described multistep procedure using the MAG3 chelate and analyzed by protein mass spectrometry for the number of chelate molecules coupled to the MAb. For biodistribution analysis, tumor-free nude mice were simultaneously injected with 186Re-, 99mTc/99Tc- and/or 125I-labeled E48 IgG and dissected 1-48 hr postinjection. RESULTS: Rhenium-186-MAb conjugates with up to 20 Re-MAG3 groups per MAb molecule were prepared with an overall radiochemical yield of 40%-60%. The conjugates did not contain empty MAG3 groups and no aggregates were formed. Only conjugates with a 186Re-MAG3:MAb molar ratio higher than 12 demonstrated slightly impaired immunoreactivity to a maximum of 15% decrease at the 20:1 molar ratio. Biodistribution experiments revealed that a proportion of the conjugate became rapidly eliminated from the blood for conjugates with a Re-MAG3:MAb molar ratio higher than 8. In this case, an increased uptake of activity was observed in the liver and intestines. The 99mTc/99Tc-MAb conjugates showed a similar enhanced blood clearance when containing more than eight Tc-MAG3 groups, while dual labeling of MAbs revealed that the in vivo stability of the conjugated Re-MAG3 complex itself does not differ from the corresponding Tc-MAG3 complex. CONCLUSION: With the method described in this study, it is possible to prepare 186Re-MAG3-MAb conjugates that fulfil all the aforementioned criteria for use in clinical RIT. Coupling of too many metal-MAG3 groups to MAbs results in rapid blood clearance. At the same metal-MAG3:MAb molar ratio, 99mTc/99Tc-MAb conjugates show a similar pharmacokinetic behavior as 186Re-MAb conjugates and can thus be used to predict the localization of 186Re-labeled MAbs and make dosimetric predictions in individual patients.

Animals↗
PubMed1996

Imaging of the larynx.

CT and MR imaging are the main modalities for examination of laryngeal pathology. In general, MR imaging seems to be the optimal method of examination in cooperative patients, especially for evaluation of their larynx prior to an attempted partial laryngectomy. CT is recommended in patients who may have rapid breathing or coughing or if MR imaging is contraindicated. The choice between the two modalities is also determined by the experience of the radiologist with these modalities. Both techniques are comparable in delineating site and extent of pathology in fat and muscular tissue. MR imaging is more sensitive than CT in detecting pathologic involvement of the cartilages. CT and MR imaging are helpful in characterization of cartilaginous tumors and benign lesions, such as laryngoceles and cysts. CT is used to assess the integrity of the laryngeal skeleton in patients who suffered from trauma, that is, for identification of occult fractures, dislocations of cartilages, or confirmation of suspected laryngeal injuries.

Humans↗
PubMed1996

Imaging of cervical lymphadenopathy.

Imaging of the neck is important to diagnose occult lesions and stage the neck in cancer patients and, to a lesser extent, help differentiate swellings in the neck. Furthermore, extension of tumors can be depicted, although assessment of operability is not very reliable. Conventional imaging techniques, such as CT, MR imaging, and US, are rapidly evolving by improvement of spatial resolution and contrast, reduction of artifacts, and development of new contrast agents. Unreliable criteria for metastases, such as size and shape, will be replaced in the future by the depiction of the microstructure inside lymph nodes and the development of specific contrast agents. US-guided aspiration is currently one of the most accurate techniques to assess occult metastases as it overcomes the criteria used by CT, MR imaging, or US without aspiration. It should be noted, however, that approximately 25% of electively operated sides of the neck contain exclusively metastases smaller than 3 mm, limiting the sensitivity in these necks to 75% for all imaging modalities. New imaging modalities, such as immunoimaging with SPECT, thallium SPECT, PET, and fused images, are rapidly developing. Although these techniques will probably become very accurate for the staging of the neck, it is doubtful whether they will be used routinely to stage the neck because of the issues of cost and availability. Their role will probably be more in the detection of unknown primaries, distant metastases, and follow-up, after radiotherapy in case of clinical doubt.

Head and Neck Neoplasms↗
PubMed1996

The relation between cancer incidence among relatives and the occurrence of multiple primary carcinomas following head and neck cancer.

Despite improvement in therapeutic modalities in head and neck squamous cell carcinoma (HNSCC) the overall survival rate has only marginally improved during the last decades. The occurrence of second primary tumors (SPTs) in the respiratory and upper digestive tract (RUDT) is the main cause of treatment failure in early stage HNSCC. Identification of risk factors for the development of SPT by epidemiological analysis may lead to better risk assessment in individual cases. Ninety-seven HNSCC patients who ultimately developed SPTs and 100 HNSCC patients who remained free of other carcinomas after treatment of the first for a minimal period of 6 years were interviewed about the incidence of RUDT carcinomas within parents and siblings. All questioned patients were smokers. Among the SPT-positive patients, 50 (8.9%) of the 562 family members were reported to have had cancer of the respiratory or upper digestive tract versus 16 (2.5%) of the 629 family members of the SPT-negative patients. This difference was statistically significant (P < 0.0001) with the stratified version of Fisher's exact test. All these 66 probands with RUDT cancer were smokers, and the percentages of smokers were similar in both proband groups. Neither age and sex of the patient, nor tumor stage influenced the occurrence of SPTs in this study. The percentages of probands with tumors outside the RUDTs were almost similar, 8.0 and 7.0% in the SPT-positive and -negative groups, respectively. Having one or more relatives with RUDT cancer was established as a risk factor (odds ratio, 3.8; 95% confidence interval, 2.0-7.6) for patients with initial HNSCC to develop an SPT. These findings suggest that, in addition to external carcinogens, an intrinsic susceptibility may influence the risk for the development of SPTs in HNSCC patients.

Carcinoma, Squamous Cell↗
PubMed1996

Lack of effect of daily N-acetylcysteine supplementation on mutagen sensitivity.

The European Organization for Research and Treatment of Cancer multicenter Euroscan trial was set up to prevent the occurrence of second primary tumors in the upper aerodigestive and respiratory tract in patients cured for early stage head and neck squamous cell carcinoma. One randomized group of patients receive daily N-acetylcysteine, an antioxidant that may be protective especially in the early steps of carcinogenesis. Mutagen sensitivity, measured as sensitivity to bleomycin in peripheral blood lymphocytes, has been found to be increased in head and neck squamous cell carcinoma and is hypothesized to reflect cancer susceptibility. The aim of this study was to investigate whether mutagen sensitivity is influenced by oral N-acetylcysteine supplementation and can therefore be used as intermediate end point in chemoprevention. Patients (n = 19) who had various periods of N-acetylcysteine supplementation (600 mg daily for 3-9 months) were analyzed. In addition, a patient group (n = 14) that did not receive N-acetylcysteine supplementation was analyzed for comparison. Our results show no evidence that administration of N-acetylcysteine did influence the mutagen sensitivity level. The only explanatory variable in the analysis of the difference between two samples of one person was the b/c value of the first measurement. Moreover, the variability in these repeated measurements (coefficient of variation of 14%) indicates that additional studies should be performed to minimize this variability and to optimize the testing of mutagen sensitivity to accurately identify individual patients at high risk for the development of multiple primary tumors.

Acetylcysteine↗
PubMed1995

Role of genetic factors in the etiology of squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine the role of genetic predisposition in the etiology of head and neck squamous cell carcinoma. DESIGN: Retrospective study. SETTING: The outpatient clinics of the departments of otorhinolaryngology and maxillofacial surgery. PATIENTS: First-degree relatives of patients with new head and neck cancer, with first-degree relatives of the patients' spouses as controls. MAIN OUTCOME MEASURE: Occurrence of cancer of the respiratory and upper digestive tract in relatives of patients with head and neck cancer and controls. RESULTS: First-degree relatives (n = 617) of 105 patients with head and neck cancer had 31 cases of cancer of the respiratory and upper digestive tract vs 10 cases in the control group (n = 618) (relative risk, 3.5; P = .0002). This higher rate of cancer was even larger in siblings (16 vs 2, relative risk, 14.6; P = .0001). CONCLUSIONS: Genetic predisposition is an important risk factor for squamous cell carcinoma of the head and neck.

Carcinoma, Squamous Cell↗
PubMed1995

Neuroendocrine neoplasms of the larynx. Importance of the correct diagnosis and differences between atypical carcinoid tumors and small-cell neuroendocrine carcinoma.

Findings in the present study have confirmed that the diagnosis of neuroendocrine tumors of the larynx (NETL) requires that a panel of neuroendocrine markers and electron microscopy be performed. This means that the clinician must be aware of the clinical presentations of such patients and should send fresh biopsy specimens to the clinical laboratory for optimal tissue studies. As shown in this study, the possibility of misdiagnosis of an atypical carcinoid tumor (ACT) is rather high. In establishing a diagnosis, a part of the material should be fixed for conventional histology, a part for immunohistochemistry and a part for electron microscopy. The correct diagnosis of NETL is obviously of great importance for subsequent treatment and prognosis. Patients with the diagnosis of ACT of the larynx require surgical treatment. Our findings also show that small-cell neuroendocrine carcinomas of the larynx should be considered to be a disseminated disease at initial presentation. A metastatic workup is necessary, but radical surgical procedures should be avoided. The combination of radiotherapy and chemotherapy is always indicated.

Aged↗
PubMed1995

Construction and characterization of the chimeric monoclonal antibody E48 for therapy of head and neck cancer.

Data from an ongoing clinical radioimmunoscintigraphy trial indicate that 99mTc-labeled monoclonal antibody (mAb) E48 is highly capable of selectively targeting squamous cell carcinoma of the head and neck (HNSCC). The percentage of the injected dose per gram of tumor tissue was found to be high, rendering mAb E48 a promising candidate mAb for therapeutic purposes. We now describe the construction of a chimeric (mouse/human) mAb E48 by recombinant DNA technology. The genes encoding the variable domains of the heavy and light chain were cloned and ligated into expression vectors containing the human gamma 1 heavy-chain gene and the human kappa light-chain gene respectively. Biological properties of the resulting chimeric mAb E48 were compared to the murine form in vitro and in vivo. The reactivities of chimeric (c)mAb and murine (m)mAb E48 with HNSCC, as assessed by immunohistochemical staining as well as immuno-blotting were shown to be similar. The affinity constant appeared to be 0.9 x 10(10) M-1 and 1.6 x 10(10) M-1 for the mmAb and cmAb respectively. The biodistribution of both antibodies was tested by simultaneous injection into nude mice bearing human HNSCC xenografts. cmAb E48 was found to be cleared more rapidly from the blood than mmAb E48, resulting in a 30% lower tumor uptake but similar tumor to non-tumor ratios, 3 days after injection. Moreover, it was shown that cmAb E48 is highly capable of lysing HNSCC targets in ADCC assays in vitro, whereas the mmAb appeared to be almost inactive. These data indicate that cmAb E48 has potential as a targeting agent for the eradication of HNSCC in man.

Animals↗
PubMed1995

Antioxidant-related parameters in patients treated for cancer chemoprevention with N-acetylcysteine.

N-acetylcysteine (NAC) is an antioxidant, possibly effective in the early steps of carcinogenesis, and is applied to prevent second primary tumours in the upper aerodigestive tract and the lungs. In this study, we evaluated the pharmacodynamic profile of 600 mg NAC treatment, given daily for 3 months. Treatment caused a significant increase of the non-protein-SH concentration in blood plasma (38%) and erythrocytes (31%). Glutathione levels in exfoliated buccal mucosa cells appeared not to be influenced by treatment. The total radical-trapping ability parameter (TRAP) of blood plasma showed no change. In vitro, the addition of glutathione, but not of NAC did increase the TRAP value. In addition, when peroxyl radicals were generated in vitro, NAC was shown to be consumed more rapidly than glutathione. This suggests that NAC prevents early damage, while glutathione functions over a longer time period.

Aged↗
PubMed1995

Value of p53 expression in oral cancer and adjacent normal mucosa in relation to the occurrence of multiple primary carcinomas.

Paraffin embedded, formalin fixed tissue sections from patients suffering from a primary oral squamous cell carcinoma were immunohistochemically investigated for the presence of p53 expression using the Bp53-11 antibody. The aim of this study was to determine the predictive value of p53 expression as a biomarker for the development of a second primary tumour (SPT) in the respiratory and upper digestive tract. In a nested case control study, neoplastic and normal tissue sections of 44 patients who had a previous history of cancer were used. 15 of the 44 had developed a SPT, while the other 29 were minimally 7 years free of disease. Additionally, nine SPTs were included in this study to establish whether concordance exists in tumours that develop in the same field. 10 of the 29 patients (34%) free of tumour during follow-up had p53 positive tumours. 8 of 15 patients (53%) who developed a SPT had a p53 positive primary tumour. This difference is not statistically different (chi 2-test). Forty percent of the total group of primary oral cavity tumours showed p53 positivity. When comparing the first and the second tumours, discordance in p53 expression between the first and second tumours was seen in 4 out of 9 cases. None of the cases showed p53 positivity in adjacent normal mucosa. In conclusion, p53 immunoreactivity in neoplasia, dysplasia and normal tissue does not predict the development of a SPT. In addition, multiple primary tumours do not have identical p53 expression.

Adult↗
PubMed1995

[Determination of genetic susceptibility for development of squamous epithelial carcinomas of the had and neck with bleomycin-induced chromosome instability].

BACKGROUND: Cigarette smoking is a well established risk factor for head and neck squamous cell carcinoma. However, data on smoking history are not sufficient to predict which patients are at high risk for the development of multiple primary tumors. It is hypothesized that both exposure to carcinogens and individual susceptibility determine cancer risk. The aim of this study was to investigate whether a possible individual susceptibility for head and neck squamous cell carcinoma was related to the outcome of the mutagen sensitivity assay, which was adopted from Hsu and colleagues. METHODS: Cultured peripheral blood lymphocytes were treated for five hours with 30 mIU/ml of bleomycin, and sensitivity was estimated by the mean number of chromatid breaks per cell scored in 100 metaphases of duplicate cultures. RESULTS: It was shown that using this standard mutagen sensitivity assay, a person's sensitivity can be reproducibly measured. Age had a significant but small contribution, whereas gender and tobacco and alcohol use had no influence on the outcome of the assay. Therefore, we consider this sensitivity for the DNA damaging effect of bleomycin constitutional. A retrospective study showed that the breaks per cell in head and neck squamous cell carcinoma patients (0.96 +/- 0.31; n = 52) were significantly higher (p < 0.001) than in control persons (0.77 +/- 0.19; n = 50). In addition, head and neck cancer patients who had already developed multiple primary tumors had a break per cell level (1.20 +/- 0.47; n = 20) which was even significantly higher (p < 0.025) than in patients with one primary tumor. CONCLUSION: We hypothesize that mutagen sensitivity reflects an individual's sensitivity vor DNA damaging agents. The extremely high sensitivity in patients with multiple primary tumors suggests that mutagen sensitivity is a phenotype reflecting a person's susceptibility to head and neck cancer. We postulate that mutagen sensitivity in combination with smoking history can be used to identify those patients at highest risk for the development of multiple primary tumors.

Adult↗
PubMed1995

The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion.

The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody-based therapy of squamous cell carcinoma in man. To anticipate the effect of high antibody dose treatment, and to evaluate the possible biological involvement of the antigen in carcinogenesis, we set out to molecularly characterize the antigen. A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells. Sequence analysis revealed that the clone contained an open reading frame of 128 amino acids, encoding a core protein of 13,286 kD. Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family. Phosphatidylinositol-specific (PI-specific) phospholipase-C treatment indicated that the E48 antigen is glycosylphosphatidylinositol-anchored (GPI-anchored) to the plasma membrane. The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region. The expression of the gene is confined to keratinocytes and squamous tumor cells. The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia. Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related. Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion.

Amino Acid Sequence↗
PubMed1995

Standardization of counting micronuclei: definition of a protocol to measure genotoxic damage in human exfoliated cells.

The proportion of exfoliated buccal mucosal cells with micronuclei gives the opportunity to assess sensitivity to gamma-radiation and genotoxic compounds and in addition to monitor the effectiveness of cancer intervention strategies. So far, results on counting micronuclei in various publications are difficult to compare because of differences in methods used, especially with regard to microscopical magnification used and number of cells counted. The aims of this study were (i) to define a protocol for counting micronuclei; (ii) to assess the feasibility of manually counting micronuclei; and (iii) the assessment of inter- and intra-patient variability of the number of micronuclei. We propose the definition of a strict protocol on counting micronuclei, with regard to cytological preparation, definition of micronuclei, instrumentation, sampling of cells in a cytological specimen and sample size. Such a strict protocol is a prerequisite for counting micronuclei in exfoliated cells to get a reproducible and sensitive indicator of exposure and for cancer risk. Although the inter- and intra-observer reproducibility of counting micronuclei per 1000 cells using such a protocol is well, we show that the variability among 10 assessments of micronuclei per 1000 cells taken sequentially from a sample size of 10,000 nuclei of the same specimen can be enormous (coefficients of variation varied in seven individuals studied between 42.1 and 102.9%). Based on the observed low frequencies varying from 1.2 to 5.2 micronuclei per 1000 cells and the variation found, we conclude that at least 10,000 exfoliated cells should be screened to monitor a significant reduction of 50% in the number of micronuclei (for a patient with an initial frequency in the micronuclei frequency range given). Since it takes approximately 7 h to evaluate this number of cells, it is also concluded that counting of micronuclei requires automation.

Acetylcysteine↗
PubMed1995

Partial vertical laryngectomy for recurrent glottic carcinoma.

Partial vertical laryngectomy for recurrent glottic carcinoma was performed in 61 patients according to stringent criteria. The great majority of the recurrent tumours appeared within 2 years of radiotherapy (80%). The mean follow-up after surgery was 79 months. At 5 years 85% of the patients were free of local recurrence. Nine patients (15%) developed a local recurrence; eight of them underwent total laryngectomy; one patient refused the operation and died. Seven patients died of other causes. The actuarial overall survival rate was 88% at 5 years. Post-operative complications were seen in 12 patients (20%); nine of these patients developed airway problems. One patient underwent total laryngectomy for severe aspiration, the others finally were decannulated. The results of this study indicate that partial vertical hemilaryngectomy for irradiation failures is a safe procedure with good results without undue morbidity.

Adult↗