Fourteen patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with 10 x 10(6) U of nonrecombinant interferon alpha (IFN) intramuscularly (IM) daily for 3 days every 28 days. There were 11 men and 3 women, with ages ranging from 48 to 74 years. Patients had previously been treated with surgery (9 patients), radiotherapy (13 patients), or chemotherapy (8 patients). All patients had measurable disease by physical exam and radiologic evaluation and a performance status of less than or equal to 2 (ECOG). Patients were treated for a minimum of 3 months and continued on therapy until disease progression. The dose and treatment schedule of IFN was well-tolerated. Toxicities included low-grade fever, mild anorexia, and malaise. Treatment was stopped in 1 patient due to the development of atrial fibrillation. One death occurred as a complication of aspiration pneumonia 2 weeks following the onset of therapy and was not felt to be related to IFN therapy. Of the 14 patients treated, there was 1 complete response (30+ months) of a base of tongue primary. Two patients had stabilization of disease (SD, 8 and 12 months). One patient had a mixed response with resolution of subcutaneous nodules. The remaining 10 patients died of progressive disease. Immunological assessment was performed on 8 patients. The 1 patient who had a complete response was noted to have markedly low pretreatment natural killer (NK) cell activity and a subsequent sharp rise in activity after initial treatment. We conclude that low-dose cyclic IFN is well-tolerated in patients with recurrent SCCHN and has potential antitumor activity.

Aged↗

PubMedDate not supplied

Structural and immunological reactivity of the principal neutralizing determinant V3 of glycoprotein gp120 of HIV-1.

The variable domain V3 in the outer glycoprotein gp120 of HIV-1 is a highly important region with respect to immune response during the course of viral infection. Neutralizing antibodies are produced against this domain: in addition, it has been shown to be a functionally active epitope for T helper and cytotoxic T cells. The high degree of amino acid variability in individual HIV-isolates, however, limits the use of the V3-domain in approaches to vaccine development. In order to characterize the residues important for antibody interaction and binding to MHC class I proteins, we constructed a consensus sequence of the V3-domain with broad reactivity [1] and used synthetic peptides derived from this consensus sequence with individual residues altered to alanine. These peptides were used as antigens in ELISA tests to define the amino acids which are important for binding to human and rabbit/anti-peptide immunoglobulins. In addition, we used these alanine-derived peptides in interaction studies with human HLA-A2.1 and mouse H-2Dd by testing their capacity to stabilize the respective MHC class I protein complexes on the surface of mutant cell lines T2 and RMA-S transfected with Dd gene. The experimental tests allowed us to define individual residues involved in antibody and MHC-protein interaction, respectively. In a further approach, we used those results to design interaction models with HLA-A2.1 and H-2Dd. Therefore, a structural model for H-2Dd was built that exhibits an overall similar conformation to the parental crystal structure of HLA-A2.1. The resulting interaction models show V3-peptide bound in an extended beta-conformation with a bulge in its centre for both H-2Dd and HLA-A2.1 complexes. The N- and C-termini of V3 peptide reside in conserved pockets within both MHC-proteins. Anchoring residues could be determined that are crucial for the binding of the respective MHC class I haplotype. The cross-reactivity of V3-peptide in enhancing the expression of two different MHC class I molecules (H-2Dd and HLA-A2.1) is shown to be based on similar peptide binding that induces an almost identical peptide conformation.

AIDS Vaccines↗

PubMedDate not supplied

Tumor dedifferentiation: an important step in tumor invasion.

Tumor invasion in vivo was studied by light and electron microscopy as well as by immunofluorescence microscopy. Special regard was paid to the grade of tumor differentiation. Dimethylhydrazine-induced murine colonic carcinomas comprising a differentiated and an undifferentiated tumor type with low and high invasiveness respectively, were used. At the invasion front of both tumor types a striking dissociation of the organized tumor cell complexes into isolated tumor cells was found together with a loss of most of the cytological features of differentiation. It is supposed that this process mobilizes the tumor cells from the main tumor bulk enabling them to invade the host tissue by active locomotion. This view is strongly supported by the demonstration of morphological equivalents of active cell movement such as pseudopodia-like cytoplasmic extrusions, adaptive changes of the cell shape and microfilament bundles. Although the proposed mechanism of tumor invasion is essentially the same in both tumor types, the grade of differentiation is nevertheless critical, as in the undifferentiated carcinomas only subtle dedifferentiation steps (loss of basement membrane and cell junctions) are necessary to acquire an invasive status. This fact may explain the comparatively high invasiveness and poor prognosis of undifferentiated carcinomas.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

Improved lensometry with a programmed calculator-lensometer combination.

The arithmetic associated with prescription calculation seems to be the major source of error and inefficiency in the performance of traditional lensometry. We have found that a programmed calculator used in combination with a lensometer achieves greater accuracy in less time than does the lensometer alone. This approach may be a useful alternative to the physician who does not wish to make a substantial investment in a fully automatic device.

Computers↗

PubMedDate not supplied

CUSUM analysis of the SCC antigen in patients with head and neck cancer.

PURPOSE: Serial postoperative serum squamous cell carcinoma antigen (SCCAg) levels in a group of head and neck cancer patients were evaluated using a cumulative sum (CUSUM) technique to determine the prognostic value of serial SCCAg levels in predicting tumor recurrence. MATERIALS AND METHODS: A retrospective analysis of serial postoperative SCCAg measurements in 75 patients with squamous cell carcinoma of the head and neck (SCCHN) from two previous studies of SCCAg was performed. Serum SCCAg levels were determined by radioimmunoassay. A V-mask was used to detect significant deviations of greater than 1 SD of the CUSUM from the reference value. SETTING: Oncologic head and neck practice at a tertiary referral hospital. PATIENTS OR OTHER PARTICIPANTS: Seventy-five consecutive patients with a minimum of three postoperative SCCAg determinations were reviewed to provide equal numbers with and without recurrent disease. All patients who remained disease-free were followed for a minimum of 2 years. All patients were previously untreated and underwent surgical therapy. MAIN OUTCOME MEASURES: CUSUM curve of postoperative SCCAg levels and 2-year disease-free survival. RESULTS: In a group of 38 patients with 2-year disease-free survival, the CUSUM analysis did not detect any significant deviation in postoperative SCCAg levels for up to 23 months after surgery. In a group of 37 patients who subsequently died of disease, a deviation of greater than 1 SD was noted as early as 5 months postoperatively and persisted throughout the course of their monitoring for up to 36 months. CONCLUSIONS: The CUSUM technique is more sensitive for detecting postoperative changes in serial measurements of the SCCAg and may be applicable to the monitoring of individual patients for recurrent disease.

Carcinoma, Squamous Cell↗