Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma.

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment.

Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.

Soluble calcium-binding proteins: parvalbumins and calmodulin from eel skeletal muscle.

1. Eel skeletal muscle contains three parvalbumin isoforms. The overall parvalbumin concentration in the muscle is 0.5 mmol kg-1 wet weight. 2. Calmodulin (0.1 mumol kg-1 wet weight) was purified by extraction with ethylenediamine tetraacetate-containing buffer, fractionation with trichloroacetic acid and separation by ion exchange chromatography on DEAE-cellulose and by molecular sieving on Ultrogel AcA 54. 3. Troponin-C-free calmodulin was obtained by fast protein liquid chromatography on a Mono Q column.

The C(2)Pi(r)-X(2)Sigma(+) Transition of BO.

The C(2)Pi(r)-->X(2)Sigma(+) electronic transition of BO has been observed in emission under high resolution. Thirty-six bands have been analyzed for (11)BO and six for (10)BO. The C state is shown to be a regular state and better constants are given. Strong perturbations are discussed on the basis of the theoretical calculations of Karna and Grein (J. Mol. Spectrosc. 122, 356-364 (1987)). Copyright 2001 Academic Press.

The Vacuum Ultraviolet Absorption Bands of the Pink Afterglow Spectrum of Molecular Nitrogen Revisited at High Resolution.

The absorption spectrum of the pink afterglow of molecular nitrogen in the vacuum ultraviolet has been analyzed at high resolution. The spectrum exhibits hot bands involving vibrational levels of the electronic ground state as high as v" = 19. Experimentally determined term values are derived for v" = 0-19, of which v" = 16-19 were before now poorly known. Copyright 1999 Academic Press.

High-Resolution Spectra of Carbon Disulfide (12)C(32)S(2) in the Region of 2 µm.

By Fourier transform, spectra were recorded for carbon disulfide (12)C(32)S(2) in the region of weak absorption near 5200 cm(-1). The data were fitted and new molecular constants were determined. We also observed a band of the isotopomer (12)C(32)S(34)S. A self-broadening coefficient gamma(0) of 0.120 cm(-1). atm(-1) was obtained by recording two lines of the nu(3)-nu(1) band with a tunable diode laser. Copyright 1999 Academic Press.

The VUV Absorption Spectrum of Lead Monoxide.

The VUV absorption spectrum of PbO vapor down to 300 Å has been observed for the first time. Four ionization energies have been determined from Rydberg series at 8.73, 8.83, 12.81, and 26.28 eV corresponding to the X(2)Pi, A(2)Sigma(+), B(2)X(+), and C(2)Sigma(+) electronic states of the PbO(+) ion. Copyright 2000 Academic Press.

The VUV Absorption Spectrum of the Tin Monoxide Molecule

The absorption spectrum of heated SnO between 2000 and 300 A has been recorded using the facilities of the SuperACO synchrotron at Orsay, France. New bands have been observed which supplement the data on the previously known systems of SnO. Newly discovered Rydberg series have confirmed the four ionization potentials observed or calculated by Dyke et al. (1982. Chem. Phys. 67, 245). Copyright 1998 Academic Press. Copyright 1998Academic Press

FT Infrared Spectra of FCN from 1200 to 1800 cm(-1) and from 2800 to 7000 cm(-1) and Global Rovibrational Analysis of the Main Isotopomers.

We measured the FT spectrum of natural FCN from 1200 to 1800 cm(-1) and from 2800 to 7000 cm(-1) with a near Doppler resolution and a line-position accuracy between 1 and 8 x 10(-4) cm(-1). Lines were assigned to 91 different bands (75 of (19)F(12)C(14)N, 11 of (19)F(13)C(14)N, and 5 of (19)F(12)C(15)N), of which no more than five had been previously reported at lower resolution. From band-by-band analyses we deduced effective state parameters. As those results complete the study of the Fourier transform spectra of natural cyanogen fluoride from 1200 to 7000 cm(-1), global rovibrational analyses of (19)F(12)C(14)N, (19)F(13)C(14)N, and (19)F(12)C(15)N have been performed on the basis of all the available experimental data about their rovibrational energies. We have so determined sets of about 100 molecular parameters for each isotopomer, and a statistical agreement was obtained. A labeling of the vibrational states is proposed on the basis of the eigenvector coefficients. Copyright 2000 Academic Press.

Fourier Transform Spectroscopy of 18O-Enriched Carbonyl Sulfide from 1825 to 2700 cm-1

We have measured the Fourier transform spectrum of carbonyl sulfide from 1825 to 2700 cm-1, using a sample enriched in both 18O (94.0%) and 17O (1.54%). A careful calibration yields a line-position accuracy between 1.5 and 3.0 10(-5) cm-1. We have observed and analyzed 118 infrared bands of which 93 are measured for the first time: 55 for 18O12C32S, 20 for 18O12C34S, 11 for 18O12C33S, 1 for 18O12C36S, 12 for 17O12C32S, 4 for 17O12C34S, 2 for 17O12C33S, and 13 for 18O13C32S. Intensities are also reported and analyzed for all those bands. The intensity accuracy is better than 10%, and the precision of approximately 1% allows us to determine some Herman-Wallis coefficients. Copyright 1998 Academic Press.

Fourier Transform Spectroscopy of Carbonyl Sulfide from 3700 to 4800 cm-1 and Selection of a Line-Pointing Program.

We have measured the Fourier transform spectrum of natural OCS from 3700 to 4800 cm-1 with a near Doppler resolution and a line-position accuracy between 4 and 8 x 10(-5) cm-1. For the normal isotopic species, 37 vibrational transitions have been analyzed for both frequencies and intensities. We also report 15 bands of OC34S, eight bands of O13CS, nine bands of OC33S, and two bands of 18OCS. Important effective Herman-Wallis terms are explained on the basis of eigenvectors. A comparison of different line-pointing programs is also presented. Copyright 1998 Academic Press.

The VUV Absorption Spectrum of the GeO Molecule.

The absorption spectrum of GeO, between 2000 and 300 Å, was recorded using the facilities of the SUPERACO synchrotron radiation in Orsay, France. The first three ionization limits, corresponding to the X(2)Sigma(+), A(2)Pi, and B(2)Sigma(+) states of the GeO(+) ion, were confirmed at 11.2814, 11.42, and 15.048 eV, respectively. The fourth ionization limit corresponding to the C(2)Sigma(+) ionic state was measured for the first time at 31.47 eV, in reasonable agreement with theoretical calculations. Copyright 1999 Academic Press.

The VUV Absorption Spectra of SiF and SiF+

The absorption spectrum of a microwave discharge (2450 MHz) in flowing helium with traces of SiF4 has been recorded on the SA61 beam line of SUPERACO between 2000 and 500 Å. Two new ionization energies have been observed at 15.12 and 17.27 eV corresponding, respectively, to the A1Pi and B1Sigma+ states of SiF+. The A1Pi <-- X1Sigma+ transition of the ion has been identified for the first time on high-resolution spectra obtained in 1992 with the 35-foot Eagle spectrograph in Meudon. Copyright 1999 Academic Press.

Rydberg States of SiCl.

A fluorescence spectrum, excited by the synchrotron radiation of Superaco in a microwave discharge through He + SiCl(4), leads to the observation of five new electronic states of SiCl, converging to the ground X(1)Sigma(+) state of the SiCl(+) ion. The (n s varsigma) and (n p pi) Rydberg series are extended respectively to n = 6 and n = 7. A new ionization limit is observed in absorption at 11.238 eV corresponding to the a(3)Pi electronic state of SiCl(+). Four new states are observed which converge to that limit. Copyright 1999 Academic Press.