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Biomedical subjects

G B Snow

Publications and source records attributed to G B Snow.

At least 145 records · Page 8Linked to original sources

Primary extranodal non-Hodgkin lymphoma of the oral cavity. An analysis of 34 cases.

34 patients with primary extranodal non-Hodgkin lymphoma (PE-NHL) of the oral cavity have been studied with reference to age, sex, clinical symptoms, location of primary tumour, histological subtype, grade of malignancy according to the Working Formulation, stage of disease, treatment and follow-up. The clinicopathological features of these oral PE-NHL correspond with those of PE-NHL in general. Survival was influenced by stage of disease and grade of malignancy.

Adolescent↗

Reconstruction of the mandible with conventional bone graft: an evaluation.

Eighteen patients with bony defects of the mandible had the mandible reconstructed using conventional nonvascularized bone grafts from the iliac crest. After surgery they received radiotherapy for cancer in the oropharynx or oral cavity. This study was carried out over a 10-year period. All patients were followed-up both for their tumour growth and the results of their reconstruction. Four to 10 years after surgery 55.5 per cent were alive and well. Full dental rehabilitation was achieved in 33 percent and 12.5 percent were without dental rehabilitation.

Adult↗

Clinical screening of monoclonal antibodies 323/A3, cSF-25 and K928 for suitability of targetting tumours in the upper aerodigestive and respiratory tract.

Immunohistochemical characterization of three monoclonal antibodies (MAbs), designated 323/A3, SF-25 and K928, on a panel of 330 head and neck and lung tumours indicated their potential for targetting tumours in the upper aerodigestive and respiratory tract. Subsequently, MAbs were screened in a clinical phase I/II radioimmunoscintigraphic (RIS) trial for the detection of primary tumours and lymphnode metastases in patients with histologically proven squamous cell carcinoma of the head and neck (HNSCC). In 10 HNSCC patients MAbs 323/A3 F(ab')2 (n = 3), chimeric (mouse-human) SF-25 IgG (n = 1), and K928 IgG (n = 6) were evaluated for their suitability for tumour targetting. Monoclonal antibodies 323/A3 and K928 were shown to be capable of detection of HNSCC. However, there was uptake at non-tumour sites, for MAb 323/A3 in the thyroid gland, liver and skeleton, probably bone marrow, and for MAb K928 in liver, spleen and the skeleton, probably bone marrow. At a higher K928 dose, uptake in the liver was diminished but still substantial. cSF-25 was not capable of detecting HNSCC, due to the rapid and extensive uptake at non-tumour sites such as liver, spleen, brain and the skeleton, probably bone marrow. Radioactivity uptake at non-tumour sites could be mainly explained by the presence of good accessible antigenic sites and will definitely limit the application of these pan-carcinoma MAbs for therapeutic purposes.

Aged↗

Carcinoma of the soft palate and anterior tonsillar pillar.

The results after treatment of a total of 52 patients between 1974 and 1990 for squamous cell carcinoma of the soft palate and anterior tonsillar pillar by surgery, radiotherapy, or a combination of the two are reported in the present study. Of the 45 patients who were treated for cure, 38 were treated by surgery, followed by radiotherapy in 19 patients (50%). Five patients received definitive radiotherapy only, and 2 were treated by other modalities such as intra-arterial methotrexate and carbon dioxide (CO2) laser. Absolute and determinant 5-year survival rates were 62% and 77%, respectively. Sixty-four percent of patients survived 5 years recurrence-free, and 27% developed multiple primary tumors in the head and neck. Tumor stages III and IV were shown to decrease survival by half compared to stages I and II. A 42% occult nodal metastases rate was observed, and 3 of 11 patients experienced regional relapse in an untreated neck. From this review it appears that surgery, combined with postoperative radiotherapy when indicated, is an effective form of treatment for carcinoma of the soft palate and anterior tonsillar pillar.

Adult↗

Surgery and postoperative radiotherapy and radiotherapy alone in T3-T4 cancers of the pyriform sinus. Treatment results and patterns of failure.

Fifty-four patients with T3-T4 squamous cell carcinomas of the pyriform sinus were treated between 1976 and 1990. Surgery with postoperative radiotherapy (n = 32) was the treatment of choice. Radical radiotherapy was used in patients with contraindications for surgery or with inoperable tumors and in patients who refused surgery. The local control rate was significantly higher in the combined treatment group (31/32; 97%) than in the group treated with radical radiotherapy (14/22; 64%) which consisted of more advanced cases. In patients who received radical radiotherapy, the highest local control rates were recorded with doses of 70 Gy and above and with the use of 2 fractions per day. There was no significant difference in regional control and survival rates between the treatment groups. New approaches are indicated to improve the prognosis of hypopharyngeal cancer.

Adult↗

[Second primary tumors following treatment of squamous cell carcinoma of the oral cavity].

In the hospital of the Free University in Amsterdam (the Netherlands) 727 patients with primary squamous cell carcinoma of the oral cavity and lip have been studied for the incidence of second primary tumors occurring in the respiratory and upper digestive tract. Out of the 727 patients, 74 (10.2%) developed a second primary tumor in these tracts. The incidence of second primary tumors was expressed per 1.000 person-years of follow-up; 28 second primary tumors per 1.000 person-years of follow-up were seen in the respiratory and upper digestive tract. The patients ran the risk of developing a second primary tumor at a steady rate of approximately 2.8% per year during at least ten years. Furthermore, an increasing incidence of second primary tumors could be observed in case of increasing use of tobacco.

Aged↗

Clinical imaging of head and neck cancer with technetium-99m-labeled monoclonal antibody E48 IgG or F(ab')2.

METHODS: In 32 patients who were suspected of having a neck lymph node metastasis from a histologically proven squamous-cell carcinoma of the head and neck (HNSCC), the diagnostic value of 99mTc-labeled (750 MBq) monoclonal antibody (1-2 mg) E48 IgG (n = 17) and its F(ab')2 fragment (n = 15) was evaluated and compared. Preoperative findings on lymph node status obtained by radioimmunoscintigraphy (RIS), computerized tomography (CT), magnetic resonance imaging (MRI) and palpation were defined per side (left and/or right side of the neck) as well as per lymph node level (I through V) and compared to the histopathological outcome of the neck dissection specimen. RESULTS: All 31 tumors at the primary site were visualized. RIS was correct in 201 of 221 levels (accuracy 91%) and in 38 of 47 sides (accuracy 81%). Fifteen levels and seven sides with limited tumor load were scored false-negative and five levels and two sides were scored false-positive. Sensitivity and specificity of RIS were similar to those of palpation, CT and MRI. The diagnostic value of RIS with E48 F(ab')2 or E48 IgG appeared to be similar. CONCLUSIONS: The present study shows that RIS with either E48 F(ab')2 or E48 IgG is as valuable as the other imaging techniques. The selective accumulation of radioactivity in tumor tissues, in combination with the known intrinsic radiosensitivity of HNSCC, justifies the development of radioimmunoconjugates for radioimmunotherapy.

Aged↗

Association between bleomycin genotoxicity and non-constitutional risk factors for head and neck cancer.

Sensitivity of phytohaemagglutinin-stimulated lymphocytes to bleomycin clastogenicity is increased in patients with tumours in organs and tissues that are in direct contact with the external environment, such as the mucosa of the head and neck. Sensitivity to bleomycin may reflect a genetically determined hypersensitivity to certain genotoxicants and therefore may be important in the carcinogenic process. In this study the applicability of bleomycin genotoxicity was investigated in cultured lymphocytes of forty individuals without a tumour history. No correlations were observed with increasing age or the well-known head and neck cancer risk factors alcohol and tobacco consumption. Since inter-individual variation in sensitivity greatly exceeded intra-individual variation, our results suggest that an elevated bleomycin clastogenicity score may identify individuals who have a constitutional hypersensitivity towards certain genotoxicants and may show an increased cancer susceptibility.

Alcohol Drinking↗

MAb U36, a novel monoclonal antibody successful in immunotargeting of squamous cell carcinoma of the head and neck.

Using viable cells of a human head and neck squamous cell carcinoma (HNSCC) cell line as immunogen, we developed monoclonal antibody (MAb) U36. Immunohistochemical examination revealed distinct surface labeling of MAb U36 with normal human squamous epithelium and squamous cell carcinomas of distinct sites of origin; head and neck, lung, esophagus, cervix, and epidermis. MAb U36 shows high affinity binding (affinity constant, 3.5 x 10(10)/M) with a cell surface antigen expressed by in vitro cultured HNSCC cell lines. Similarity of the reactivity profiles of MAb U36 and MAb E48, currently the most promising antibody described for specific targeting of HNSCC in patients, warranted further comparison of these MAbs. MAb U36 recognizes a M(r) 200,000 antigen, which is different from the MAb E48 defined antigen. Furthermore, comparison of immunohistochemical staining patterns of MAb U36 and MAb E48 on a broad panel of primary HNSCC sections revealed more extensive staining for MAb U36: more tumors showed reactivity with MAb U36 and more tumor cells per tumor showed positive reaction, and staining was found to be more intense. MAb U36 does not show cross-reactivity with mouse, rat, pig, sheep, or bovine tongue epithelium. As a first approach to evaluate the suitability of MAb U36 for tumor targeting in vivo, radiolabeled MAb U36 was administered to athymic nude mice bearing human HNSCC xenografts on both flanks. Selective tumor accumulation of the radioimmunoconjugate was observed. Mean tumor uptake (in percent injected dose/g wet-weight of tissue) of MAb U36 at days 1, 2, 3, 5, 7, and 12 was 15.1, 17.9, 24.0, 21.0, 25.8, and 16.0%, respectively. The tumor to blood ratio at day 1 was 0.9 and increased up to 3.8 at day 12. The tumor uptake at day 12 was at least 10 times higher when compared to other tissues. The corollary of these findings is that MAb U36 harbors high potential for specific targeting of HNSCC.

Animals↗

186Re-labeled monoclonal antibody E48 immunoglobulin G-mediated therapy of human head and neck squamous cell carcinoma xenografts.

In our laboratory, a solid-phase synthesis of 186Re-mercaptoacetyltriglycine for reproducible and aseptic production of stable 186Re-monoclonal antibody conjugates was recently developed. Monoclonal antibody (MAb) E48 IgG, when labeled with 99mTc according to the same labeling procedure, was recently shown to be highly capable of detecting recurrent and metastatic disease in patients with head and neck squamous cell carcinoma. In the present study, MAb E48 was labeled with 186Re and tested for its capacity to eradicate established human head and neck squamous cell carcinoma xenografts growing s.c. in nude mice. Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) microCi 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8). In the 200 microCi group, 5 of 11 tumors showed regression while the remaining tumors showed a decreased growth rate. In the other treatment groups, all tumors regressed. In all treatment groups, remissions were observed (no regrowth within 4 months after injection). The number of remissions in the 200, 400, 500, and 600 microCi group were 2 of 11 (18.2%), 3 of 11 (27.3%), 6 of 12 (50%), and 3 of 9 tumors (33.3%), respectively. In comparison with the median tumor volume doubling time of the controls, the tumor volume doubling time in the remaining tumors in the groups receiving 200, 400, 500, or 600 microCi was increased 5.5-, 7.8-, 8.7-, and 11.3-fold, respectively. Dosimetry was based on the biodistribution of 200 microCi 186Re-labeled MAb E48 IgG. In the group receiving 600 microCi, the absorbed cumulative radiation dose was 3432 cGy for tumor and 1356 cGy for blood. In other tissues, the accumulated dose was < 17% of the dose delivered to tumor. The whole-body dose was 11-fold lower than the dose delivered to tumor. Apparent toxicity was limited to weight loss, which did not exceed 12% and which returned to control levels within 2 weeks. No treatment-related deaths occurred. These data suggest radioimmunotherapy with 186Re-labeled MAb E48 IgG to be a feasible approach for the treatment of head and neck cancer.

Animals↗

Head and neck cancer.

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Combined Modality Therapy↗

A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as potential intermediate endpoints in chemoprevention trials.

BACKGROUND: Patients with squamous cell carcinoma of the head and neck have a 10-30% risk of developing a second primary tumor. The concept of "field cancerization" assumes that the whole upper aerodigestive tract is affected and prone to malignant transformation. This study was undertaken to investigate the value of a panel of monoclonal antibodies to identify biomarkers in oral mucosa associated with cancer risk. Such biomarkers may be suitable candidates to serve as intermediate endpoints in cancer chemoprevention trials. METHODS: As a model, the expression of antigens was assessed in cytologic preparations obtained from macroscopically normal oral mucosa of patients with tongue carcinoma and of controls. The panel consisted of antibodies against cytokeratin 8, 10, 13, and 19 and the monoclonal antibodies designated K931, K984, E48, Ki-67, and UM-A9. RESULTS: Oral mucosa of cancer patients had a more than threefold increased expression of cytokeratin 19 as compared with controls (36.0 versus 11.3%; P < 0.01). CONCLUSION: Cytokeratin 19 is a potential intermediate endpoint in head and neck cancer chemopreventive trials.

Adult↗

Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma.

BACKGROUND: The incidence of distant metastases in head and neck cancer patients is rising because of greater locoregional control of the disease. METHODS: The relative risks for having distant metastases as first site of failure relative to the regional lymph node involvement were determined. RESULTS: The overall incidence was 10.7%, with a clear relationship between the number of involved lymph nodes and extranodal spread on one hand, and distant spread on the other hand. The group with histopathologic presence of disease in the neck had twice as much distant metastases as did those with histopathologic absence (13.6% versus 6.9%). Patients with more than three histologically positive lymph nodes were most at risk for having distant metastases (46.8%). The presence of extranodal spread meant a threefold increase in the incidence of distant metastases, compared with patients without this feature (19.1% versus 6.7%). CONCLUSIONS: Patients with three or more positive nodes and with extranodal spread may benefit from adjuvant systemic therapy.

Adult↗

Total glossectomy with laryngeal preservation.

OBJECTIVE: To evaluate the results of a planned combined therapy with surgery and postoperative radiotherapy in the management of large (T3 to T4) squamous cell carcinomas of the tongue-tongue base in properly selected patients. PATIENTS AND METHODS: Twenty-one patients underwent this procedure in a 4-year period. The selection criteria were directed to identify those patients in whom laryngeal preservation was feasible and who were motivated. Five categories of patients were included: those with (1) large primary tumors of the tongue-tongue base; (2) recurrence after initial radiotherapy, brachytherapy, chemotherapy, or a combination of these modalities; (3) recurrence after initial surgery and radiotherapy; (4) double primary tumors; and (5) second or third primary tumors arising in the tongue or base of the tongue. Preoperative investigation included examination under anesthetic and magnetic resonance imaging. Depending on the proximity of the primary tumor to the mandible, a mandibular split, a marginal resection, or a segmental resection was carried out. Soft-tissue replacement was achieved by a myocutaneous or a muscle flap of the pectoralis muscle with split skin. Whenever possible tissues of the contralateral floor of the mouth were also used. Laryngeal suspension was performed in all cases. Postoperative radiotherapy consisted of megavolt therapy, 66 Gy in 6 weeks to the primary site and both sides of the neck. RESULTS: Resumption of swallowing and speech was achieved in all patients. External deformity was slight. Patients were able to return to their families. CONCLUSIONS: Total glossectomy with laryngeal preservation in properly selected patients provides local and regional control and preserves quality of life.

Adult↗