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Biomedical subjects

G L Clayman

Publications and source records attributed to G L Clayman.

89 records · Page 5Linked to original sources
PubMed1992

Acute-phase proteins in patients with head and neck cancer treated with interleukin 2/interferon alfa.

Circulating acute-phase proteins may mediate adverse reactions in patients receiving biologic response modifiers, including inhibition of immune responsiveness and clinical toxic effects. Nine patients with unresectable head and neck squamous cell carcinoma were prospectively examined for levels of acute-phase proteins during interleukin 2/interferon alfa immunotherapy and for clinical toxic effects. Simultaneous determination of the in vitro immunomodulatory capacity of autologous serum on the induction of lymphokine-activated killer cells was assessed in 4-hour chromium release assays. Of the seven acute-phase proteins analyzed, haptoglobin and C-reactive protein levels were elevated before therapy was started. Toxic events leading to cessation of interleukin 2/interferon alfa therapy had a high correlation with elevated C-reactive protein and lowered C3 component of complement levels. No relationship was noted between serum levels of acute-phase proteins and induction inhibition of lymphokine-activated killer cell cytotoxicity. The role of C-reactive protein and complement degradation products in mediating interleukin 2/interferon alfa toxicity requires further investigation.

Acute-Phase Proteins↗
PubMed1992

A phase II study of interleukin-2 and interferon-alpha in head and neck cancer.

The capacity to modulate host response against metastatic head and neck cancer may eventually lead to improved survival. This phase II study in patients with advanced head and neck cancer evaluated the efficacy of combination systemic recombinant interleukin-2 (IL-2) and interferon-alpha (INF-a) and evaluated laboratory correlates between tumor response and a) tumor differentiation and b) NK cell activation. Five of fourteen patients responded; two had partial responses and three had transient responses (one complete and two partial, each lasting less than four weeks). Patients that responded had relatively lesser tumor burden and poorly-differentiated metastases. No response was observed in those few individuals in whom natural immune function was only minimally enhanced by therapy. Major toxicity, including but not limited to fever, fatigue and pulmonary compromise, allowed only 3 of 14 patients to complete three cycles of therapy. This preliminary phase II study shows that combination IL-2/INF-a therapy has clinical anti-tumor activity and that the level of NK cell activation and the degree of tumor differentiation may correlate with response.

Adult↗
PubMed1992

Detection of regulatory factors of lymphokine-activated killer cell activity in head and neck cancer patients treated with interleukin-2 and interferon alpha.

Interleukin-2 (IL-2) and interferon-alpha (INF-alpha) are biologic modifiers that have met with limited clinical success in the treatment of human malignancies. We conducted a phase 2 trial of IL-2-IFN-alpha in patients with advanced or unresectable squamous cell carcinoma of the upper aerodigestive tract. Two patients were analyzed sequentially for serum induction phase-blocking factors of lymphokine-activated killer (LAK) cell activity in their therapy. Serum also modulated LAK activity independent of autologous or allogeneic effector cells. Significantly inhibitory serum samples were stable in multiple freezings and thawings. Heat-treating the inhibitory serum, at 56 degrees C for 30 minutes, only partially removed the serum inhibitory capacity. Sequential analysis of p55 and p75, subunits of IL-2 receptors, showed that absence of effector cell lytic activity was associated with markedly decreased fluorescence of the IL-2Rp75 subunit only. No significant alteration of the IL-2Rp55 subunit occurred with therapy. These studies support the theory that lymphocyte and multiple serum factors, developing during IL-2-IFN-alpha therapy, regulate the induction of in vitro LAK activity. Further understanding of these factors may lead to improvements in biologic modifier therapy.

Aged↗
PubMed1991

Immunomodulation of the induction phase of lymphokine-activated killer activity by acute phase proteins.

Effective treatment of head and neck cancer with biologic response modifiers may be benefitted by an understanding of in vivo factors capable of modulating the lymphokine-activated killer (LAK) cell phenomenon. Eighteen patients with squamous cell carcinoma of the head and neck were studied. Killer cells from each patient, activated by recombinant interleukin-2 (10 U/ml), were induced in either complete medium alone or complete medium plus 10% autologous serum solution and analyzed. Cytotoxicity against both K562 and squamous cell carcinoma (MDA686-Ln) cell lines was determined by use of standard chromium-release assays. The immunomodulatory capacity of serum was correlated with levels of various acute phase proteins. Autologous serum significantly inhibited the induction phase of the LAK phenomenon in 61% of patients and stimulated it in 22%. No patients with early stage I or II disease had significant inhibition of induction. No direct correlation between inhibition and serum acute phase protein levels were seen. An inverse relationship was seen between the C3 component of complement and induction inhibition (r = -0.6). These findings suggest that advances of in vivo immunomodulatory therapy will require elucidation of mechanisms of serologic inhibition of the induction phase of the LAK phenomenon. Such studies may lead to serologic modification to enhance treatment efficacy of biologic response modifiers.

Acute-Phase Proteins↗
PubMed1991

Intracranial complications of paranasal sinusitis: a combined institutional review.

Intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies. The charts of all patients (n = 649) admitted for acute or chronic sinusitis to the University of Minnesota Hospital and to the University of Michigan Medical Center during a 13-year period (1975 to 1988) were retrospectively reviewed to determine the incidence of complications. The clinical presentation, bacteriology, involved sinuses, influencing host factors, white blood cell count on presentation, length of hospitalization, and postinterventional complications are presented. Twenty-four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3.7%. Aggressive medical and semi-emergent surgical intervention are required to prevent excessive morbidity and/or mortality. Intracranial complications included subdural empyema, frontal lobe abscesses, intrahemispheric abscesses, cavernous and superior sagittal sinus thrombosis, and osteomyelitis.

Adolescent↗
PubMed1990

Serologic determinants of survival in patients with squamous cell carcinoma of the head and neck.

Specific circulating serum proteins may reflect unique properties governing the growth and progression of head and neck cancers. One hundred three previously untreated patients with squamous cell carcinoma of the head and neck were prospectively evaluated for serum IgA, IgG, and IgM and C1q-binding macromolecules. Immunoglobulins were assessed by the immunoturbidimetric technique. C1q-binding macromolecules (C1qBM) were measured utilizing the iodine-125 assay of Zubler et al (J Immunol 1976; 116: 232-5). Neither the level of serum immunoglobulins nor C1qBM values were correlated with the primary site, AJC (American Joint Committee on Cancer) stage of disease, or size of primary lesion. Likewise, comparison of serum IgA with C1qBM values demonstrated that these laboratory parameters were independent variables (r = 0.15 by Pearson linear regression). Univariate statistical analysis, utilizing the Cox proportional hazard model, showed serum IgA and C1qBM values to each contribute significantly to the ability to predict survival in patients with advanced squamous cell carcinoma of the head and neck (p = 0.01 and 0.003, respectively). Furthermore, multivariate analysis reveals that both C1qBM and serum IgA levels contribute significantly to the hazards model beyond staging in predicting survival (p less than 0.001). Predictive results were most apparent in patients with stage IV disease and related to the probability of both regional and distant metastatic recurrences. Conversely, serologic analysis provided no information in patients who were staged early. These results support pretreatment multiparametric serologic analysis of patients with squamous cell carcinoma of the head and neck.

Adult↗
PubMedDate not supplied

Early squamous cell carcinoma of the hypopharynx: outcomes of treatment with radiation alone to the primary disease.

BACKGROUND: This retrospective study analyzes the outcome of treatment of a cohort of patients with hypopharyngeal tumors staged T1 or T2 treated with curative radiation alone to the primary tumor. The potential influence of advances in technology and radiobiology are studied. METHODS: Eighty-two patients with early-stage (T1, 19 patients; T2, 63 patients) hypopharyngeal squamous cell carcinomas treated between 1976 and 1992 at the University of Texas M.D. Anderson Cancer Center completed a course of definitive radiotherapy to their primary tumors. Forty-three patients (52%) were node positive, of which 23 (28%) had surgery to their involved necks in addition to radiation. Thirty-six patients (44%) had computerized tomography (CT) as part of the staging workup. Doses to the primary ranged from 60 to 79 Gy. Forty-four patients (54%) in this study were treated with twice-daily radiation (BID). Boosts to gross disease using off spinal cord fields were treated with Co60 gamma rays in 40 patients (49%); 34 (41%) with 6-25 MV x-rays (X), and 8(10%) with an ipsilateral electron beam field. RESULTS: The 2-year actuarial local control rates for patients with T1 and T2 disease were 89% and 77%, respectively. Subgroup analysis of T2 patients showed the following differences in actuarial local control rates at 2 years: BID, 86%; no BID, 60% (p, .004%); CT, 83%; no CT, 71% (p, .1); X boost, 88%; no X boost, 67% (p, .04). The actuarial 2- and 5-year survival rates for all patients were 72% and 52%, respectively. CONCLUSIONS: A majority of patients with early hypopharyngeal lesions are radiocurable. Patients treated with hyperfractionated radiotherapy and off spinal cord fields with 6 MV (or higher energy) x-ray beams had improved local control rates. CT scans assisted in appropriate patient selection for definitive treatment with radiation.

Actuarial Analysis↗
PubMedDate not supplied

Expression of galectins in head and neck squamous cell carcinoma.

BACKGROUND: Galectins are carbohydrate-binding proteins thought to be important for cell growth and differentiation, whose expression is altered in some tumors with aggressive phenotype. Our objective was to evaluate the expression of galectins in head and neck squamous cell carcinoma (HNSCC). METHODS: Fourteen HNSCC cell lines and four primary tumor specimens were evaluated using immunoblotting, and immunohistochemical analysis was performed on 35 primary HNSCCs. RESULTS: Galectin-1 and galectin-3 were expressed in most HNSCC cell lines and primary tumor specimens. Galectin-1 was detected in the basal layer of normal adjacent mucosa, in connective tissue stroma, and at the periphery of invasive tumor islands. Galectin-3 localized to superficial mucosal layers, and adjacent to keratin pearls in invasive carcinoma. CONCLUSIONS: Galectins are manifested in HNSCC tumors and are localized to the cell surface, where they may participate in cellular interactions. The expression pattern of galectins appears to be associated with degree of squamous differentiation, suggesting a potential role for galectins as biologic and differentiation markers in HNSCC.

Antigens, Differentiation↗
PubMedDate not supplied

Modifications of the mandibular swing for preservation of occlusion and function.

The mandibular swing, or midline mandibular osteotomy with lateral mandibular displacement, provides excellent exposure equivalent to that obtained by composite resections of the mandible while minimizing cosmetic and functional disability and reducing the complexity of reconstruction. This procedure is most commonly described from an oncologic standpoint. Modifications of this procedure, performed on patients with adequate anterior mandibular height, provide access to lesions of the skull base, as well as benign lesions of the parapharyngeal space. Minor modifications of the midline mandibular osteotomy, as well as preservation of anterior mandibular dentition, provide these patients with immediate restitution of interocclusal anatomy and function.

Dental Occlusion↗
PubMedDate not supplied

Resection of advanced cervical metastasis prior to definitive radiotherapy for primary squamous carcinomas of the upper aerodigestive tract.

Thirty-five previously untreated patients with stage IV squamous cell carcinoma of the upper aerodigestive tract with advanced neck disease (mass greater than 3 cm) but with primary lesions thought to be locally controllable with radiotherapy were selected between 1972 and 1988 for treatment by neck dissection followed by radiotherapy; postoperative to the neck and definitive to the primary. Limited neck dissections spared muscles, nerves, and vasculature structures unless clinically involved with cancer. All patients received at least 50 Gy, postoperatively, to the entire neck with doses of up to 75 Gy being delivered to the primary treatment portals. Regional (neck) failure occurred in 11% (4 of 35) patients. Overall, 5-year survival from cancer was 55%. Multiple levels of neck involvement were associated with poorer survival than a single large node; however, the difference was not statistically significant. Delay in the institution of radiotherapy following surgery adversely affected survival (p = 0.01). This study demonstrates that in selected patients it is possible to resect advanced nodal metastasis prior to treating the primary with radiotherapy without compromising cancer control.

Adult↗
PubMedDate not supplied

Bacteriologic profile of surgical infection after antibiotic prophylaxis.

Wound infections resulting from contamination during major head and neck surgery continue to be a critical issue. In this study, specimens of pus or draining fluids from the wounds of 43 surgical patients who received perioperative administration of ampicillin/sulbactam or clindamycin were cultured for aerobic and anaerobic isolates to species level. Polymicrobial infections were identified in 13 of 43 patients (30%); 82% of isolates were aerobic organisms (45 of 55), and 18% were anaerobic or facultative species (10 of 55). Nine of 43 patients (21%) showed no bacterial isolates from cultured material. Independent of the primary site of malignancy or antibiotics used, nine of 25 isolates (36%) obtained from patients who underwent concomitant dental extractions, but only one of 24 (4%) who did not, developed anaerobic infections, (p < 0.001). The minimum inhibitory concentration of anaerobic isolates suggested sensitivity to the antibiotics used, and minimum bactericidal concentration data suggested that further postoperative doses may be required to adequately treat the heavily contaminated wounds. These data suggest that wound colonization following dental extraction procedures in clean contaminated head and neck surgery increases the risk of anaerobic infections. The use of a therapeutic dose and longer duration of perioperative antibiotics may be warranted.

Ampicillin↗
PubMedDate not supplied

Gene therapy for head and neck cancer.

BACKGROUND: Molecular or gene therapy involves the introduction of genetic material (DNA) into host cells to induce the expression of the therapeutic product of that gene. This ability to transfer genetic material provides a novel approach for the investigation and potential treatment of a variety of both inherited and acquired diseases. METHODS: This review summarizes the principles of molecular therapy and potential strategies for its use in the treatment of solid malignancies. Some molecular therapy strategies permanently integrate the gene into the targeted cells, whereas others induce only transient expression of a therapeutic gene product. Initial clinical studies in gene therapy are being closely regulated for public safety by both the National Institutes of Health Recombinant DNA Advisory Committee and the U.S. Food and Drug Administration. CONCLUSIONS: These studies will provide insight into further applications of gene therapy and novel molecular interventions that may alter our management of solid malignancies; they may also reveal mechanisms for preventing or reversing the carcinogenic process.

DNA, Recombinant↗
PubMedDate not supplied

Apoptosis induction by E2F-1 via adenoviral-mediated gene transfer results in growth suppression of head and neck squamous cell carcinoma cell lines.

E2F-1, a transcription factor by discovery, is thought to play a crucial role in regulating G1/S cell cycle progression. Its activity is modulated by complex formation with the retinoblastoma protein and related proteins. Overexpression of E2F-1 has been shown to induce apoptosis in quiescent fibroblasts. We constructed a recombinant E2F-1 adenovirus to test whether an overexpression of E2F-1 in head and neck squamous cell carcinoma cell lines would also induce apoptosis. Two cell lines, Tu-138 and Tu-167, were chosen for use in this study. Both cell lines harbor p53 mutations but express different levels of the retinoblastoma protein. Upon E2F-1 adenovirus infection, both cell lines expressed elevated levels of E2F-1 protein and then activated a pRb-chloramphenicol acetyltransferase reporter construct containing an E2F-1 binding motif. In vitro growth assay demonstrated that growth suppression by the E2F-1 protein was effective on both cell lines. Results from DNA fragmentation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analyses indicated apoptosis induction in cells infected with AdCMV-E2F-1. Moreover, ex vivo experiments in nude mice showed total suppression of tumor growth at sites that received cells infected AdCMV-E2F-1. An in vivo analysis of apoptosis using in situ end-labeling further demonstrated the induction of apoptosis by AdCMV-E2F-1 in tumor-bearing animals. These data indicate that overexpression of E2F-1 via an adenoviral vector suppresses in vitro and in vivo growth of head and neck squamous carcinoma cell lines through induction of apoptosis.

Adenoviridae↗