p53 serum antibodies as prognostic indicator in head and neck cancer

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The post-therapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer. Received: 5 December 1996 / Accepted: 4 January 1997     

Histopathological lesions of molluscs in the harbour of Norderney,Lower Saxony,North Sea (Germany)

During a combined research project at several stations along the Lower Saxony coast (German North Sea) antifouling biocides were analysed in water, sediment and biota. Pathological alterations in blue mussel, Pacific oyster and periwinkle found in the harbour of Norderney and a reference station are presented here and discussed on the background of chemical analyses. The molluscan species from the reference station Borkum East flat did not show any pathological effects in central organs, except those provoked by an infestation in the gastro-intestinal tract by the copepod Mytilicola intestinalis and trematode larvae. In most animals, the metacercaria were found in the interstitial tissue without any inflammatory reaction. In a minor number of specimens, an inflammatory reaction in the mucosa and sub-mucosa of the intestine occurred in association with Mytilicola infestation. These reactions may be evoked through mechanical irritation of the gut epithelium, metabolic products of the parasites or invading bacteria. In contrast to the observed pathological changes of mussels, oysters and periwinkles in Norderney harbour were not found to be associated with parasitic infestation. The most prominent pathological alterations were observed in the digestive system and in the gonad. In the gastro-intestinal tract inflammatory reactions, atrophy and necrosis of tubules in the mid gut gland were most pronounced in spring at the beginning of the pleasure boat season in the Pacific oyster and to a minor degree in the blue mussel and the periwinkle. The latter displayed additional inflammatory and necrotic processes in the gills. Especially in the gonad, an elevated resorption rate of gametes was present in the Pacific oyster and in the periwinkle. In addition, impact of organotin compounds was reflected in an intersex index of up to 1.4 in Littorina littorea in coincidence with masculinization of the reproductive organs.     

Validating cancer drug targets through chemical genetics

Targeted therapies for cancer promise to revolutionize treatment by specifically inactivating pathways needed for the growth of tumor cells. The most prominent example of such therapy is imatinib (Gleevec), which targets the BCR–ABL kinase and provides an effective low-toxicity treatment for chronic myelogenous leukemia. This success has spawned myriad efforts to develop similarly targeted drugs for other cancers. Unfortunately, the high expectations of these efforts have not yet been realized, likely due to the genetic diversity among and within tumors, as well as the complex and largely unpredictable interactions of drug-like compounds with innumerable targets that affect cellular and organismal metabolism. While improvements in sequencing technologies are beginning to address the first problem, solving the second problem requires methods for linking specific features of the cancer genome to their optimally targeted therapies. One approach, referred to as chemical genetics, accomplishes this by genetic control of chemical susceptibility. Chemical genetics is a crucial tool for the rational development of cancer drugs.     

Osmotic adjustment of Zymomonas mobilis to concentrated glucose solutions

Summary The physiological basis of the exceptionally high sugar tolerance of Zymomonas mobilis was investigated. Determinations of the internal metabolite concentrations of Z. mobilis showed that an increase in the extracellular glucose concentration was accompanied by a parallel rise in the intracellular glucose concentration, bringing about an almost complete osmotic balance between internal and external space. Studies of glucose transport confirmed that Z. mobilis has a facilitated diffusion system which enables a rapid equilibration between internal and external glucose concentrations. Studies using the non-metabolisable sugars maltose (impermeable) and xylose (permeable) revealed that these sugars were able to alter the osmotic pressure on the cytoplasmic membrane resulting in volume changes.Dedicated to Professor R. K. Finn on the occasion of his 70th birthday