Conformal radiotherapy of maxilla tumors

PURPOSE: To demonstrate a conventional and a new therapeutic method of 3D treatment planning in maxilla tumors, the process of 3D treatment planning and its significance and to compare these two methods. METHOD: We performed 2D and 3D treatment plans. The ADAC planning system was used in the 3D treatment planning. CT and MRI scans were taken on the target volume and on each scan we demarcated the target volume and the critical organs. The irregular fields were obtained by 3D graphic reconstruction provided by the treatment planning programme. RESULTS: Compared to the conventional treatment planning more favourable dose distribution was obtained within the target volume and the radiation burden of the critical organs was kept under their tolerance doses. CONCLUSION: In conformal 3D treatment planning the shape and size of the irradiated volume are in good conformity with those of the target volume. In this way the radiation burden of the critical organs and adjacent intact tissues can be reduced.     

Importance of 3D conformal percutan and brachytherapy treatment planning based on CT and MRI examinations in treatment of oral cavity tumors

AIM: The importance of 3D conformal percutan and brachytherapy treatment planning based on CT and MRI examinations in treatment of oral cavity tumors. Introducing of the planning procedure and the selection aspects. METHOD: We present the treatment planning based on CT and MRI slices of an oral cavity tumor. The percutan or interstitial boost follow the percutan irradiation of the involved regions and lymph nodes, regarding to the target volume and the critical organs. RESULT: Our ADAC 3D planning system gives us the possibility to add the first line and the boost treatment plans, to determine and compare the dose distribution within the planned target volume and the radiation load of the critical organs. CONCLUSION: The comparative 3D radiation planning system allows higher local dose escalation required for the effective radiation treatment of oral cavity tumors with maximal protection of the surrounding healthy tissues.     

Therapy of multiple myeloma

Multiple myeloma (MM) is a haematological malignancy characterised by the clonal expansion of malignant plasma cells within the bone marrow. It accounts for 10% of all haematological malignant diseases and 1% of all malignancies. The median age of patients at the time of the diagnosis is 70 years. The characteristic clinical features of MM are bone marrow failure, susceptibility to infections, bone pain, pathological bone fractures, hypercalcaemia, and renal failure. Though MM is currently incurable, the important progress in chemotherapy has resulted in an improvement in survival from a median of 7 months in the 1950-ies to about 3 years today. Advances in the diagnosis and in supportive treatment of infections, hypercalcaemia, and renal failure also contributed to the prolongation of survival. For decades, the gold standard of treatment had been oral melphalan alone or in combination with prednisolone. Combination chemotherapy has not improved overall survival (OS), but these regimens have led to the prolongation of event-free survival (EFS) and also to a better quality of life. High-dose chemotherapy with haemopoietic stem cell rescue resulted in a great improvement in EFS as well as OS. For those very few who have an HLA-compatible donor and are under 55, allogeneic bone marrow transplantation offers the best hope of survival but comes at a greatly increased risk of toxicity. There are conflicting data in the literature concerning the role of interferon-alpha; it seems to be able to prolong the duration of the plateau phase. Current treatment is moving towards an approach using sequential therapy. This involves induction therapy proceeding to high-dose chemotherapy with some form of stem-cell rescue. Bisphosphonates reduce hypercalcaemia, bone pain and can inhibit bone destruction. They also possess a direct antitumor activity. The better understanding of the pathomechanism of the disease gives the opportunity of the application of new therapeutic modalities such as antagonising the effect of interleukin-6 (IL-6), or idiotypic vaccination.     

Hypothyroidism in Hodgkin's disease patients

PURPOSE: Study of thyroid function in Hodgkin's disease patients in complete remission. PATIENTS AND METHODS: We examined the thyroid function of 160 Hodgkin's disease patients in complete remission for at least one year, and determined the values of supersensitive thyroid stimulating hormone (sTSH), free T4 (fT4), free T3 (fT3) hormones. RESULTS: Normal values were observed in 117 patients, subclinical change (only elevated sTSH) in 28 patients, clinical hypothyroidism in 14 patients (also low fT4 and/or fT3), hyperthyroidism (Basedow's disease) in one patient. Hypothyroidism was one and a half times more frequent in females than in males. The normal and low thyroid function group did not differ from each other in mean age, histological subtypes, disease stage, general symptoms, and whether lymphangiography was performed. Hypothyroidism was more frequent in patients who had undergone mantle or neck radiotherapy. The onset of thyroid gland underfunction was more pronounced from six years after neck radiotherapy. The thyroid disease could be controlled using a daily dose of 25-225 mg levothyroxin. CONCLUSIONS: During the care of Hodgkin's disease patients routine examination of the thyroid function is important for the early recognition and prevention of treatment related late complications. On the other hand in treatment planning phase more attention should be paid to thyroid gland protection when neck radiotherapy is used.     

Effect of endorphin exposure at weaning on the endorphin and serotonin content of white blood cells and mast cells in adult rat

Hormonal imprinting takes place perinatally at the first encounter between the developing receptor and its target hormone, resulting in the accomplishment of normal receptor development. In the presence of an excess of target hormone or the absence of it, or an excess of related molecules which can be bound by the receptor, faulty imprinting develops with life-long consequences. In previous experiments neonatal endorphin exposure caused a decrease in endorphin and serotonin content of peritoneal mast cells of adult animals. In the present experiment 25-day-old (weaned) female rats received 2 microg endorphin, and the endorphin as well as serotonin content of adult mast cells and white blood cells was studied by flow cytometry and confocal microscopy. Peritoneal lymphocytes and blood monocytes contained significantly (p<0.01) less endorphin and peritoneal mast cells less serotonin (p<0.07, i.e. of questionable significance) than the untreated control. The results bring attention to the possibility of durable imprinting of differentiating cells later in life and to the durable (possibly life-long) effect of an endorphin excess (perhaps caused by injury) manifested in the change of endorphin and serotonin content of immune cells.     

Definition of a short region of XPG necessary for TFIIH interaction and stable recruitment to sites of UV damage

XPG is the human endonuclease that cuts 3' to DNA lesions during nucleotide excision repair. Missense mutations in XPG can lead to xeroderma pigmentosum (XP), whereas truncated or unstable XPG proteins cause Cockayne syndrome (CS), normally yielding life spans of <7 years. One XP-G individual who had advanced XP/CS symptoms at 28 years has been identified. The genetic, biochemical, and cellular defects in this remarkable case provide insight into the onset of XP and CS, and they reveal a previously unrecognized property of XPG. Both of this individual's XPG alleles produce a severely truncated protein, but an infrequent alternative splice generates an XPG protein lacking seven internal amino acids, which can account for his very slight cellular UV resistance. Deletion of XPG amino acids 225 to 231 does not abolish structure-specific endonuclease activity. Instead, this region is essential for interaction with TFIIH and for the stable recruitment of XPG to sites of local UV damage after the prior recruitment of TFIIH. These results define a new functional domain of XPG, and they demonstrate that recruitment of DNA repair proteins to sites of damage does not necessarily lead to productive repair reactions. This observation has potential implications that extend beyond nucleotide excision repair.     

The alternative<Emphasis Type="SmallCaps"> d</Emphasis>-galactose degrading pathway of<Emphasis Type="Italic"> Aspergillus nidulans</Emphasis> proceeds via<Emphasis Type="SmallCaps"> l</Emphasis>-sorbose

The catabolism of d-galactose in yeast depends on the enzymes of the Leloir pathway. In contrast, Aspergillus nidulans mutants in galactokinase (galE) can still grow on d-galactose in the presence of ammonium—but not nitrate—ions as nitrogen source. A. nidulans galE mutants transiently accumulate high (400 mM) intracellular concentrations of galactitol, indicating that the alternative d-galactose degrading pathway may proceed via this intermediate. The enzyme degrading galactitol was identified as l-arabitol dehydrogenase, because an A. nidulans loss-of-function mutant in this enzyme (araA1) did not show NAD⁺-dependent galactitol dehydrogenase activity, still accumulated galactitol but was unable to catabolize it thereafter, and a double galE/araA1 mutant was unable to grow on d-galactose or galactitol. The product of galactitol oxidation was identified as l-sorbose, which is a substrate for hexokinase, as evidenced by a loss of l-sorbose phosphorylating activity in an A. nidulans hexokinase (frA1) mutant. l-Sorbose catabolism involves a hexokinase step, indicated by the inability of the frA1 mutant to grow on galactitol or l-sorbose, and by the fact that a galE/frA1 double mutant of A. nidulans was unable to grow on d-galactose. The results therefore provide evidence for an alternative pathway of d-galactose catabolism in A. nidulans that involves reduction of the d-galactose to galactitol and NAD⁺-dependent oxidation of galactitol by l-arabitol dehydrogenase to l-sorbose.     

AII amacrine neurons of the rat retina show diurnal and circadian rhythms of parvalbumin immunoreactivity

We investigated parvalbumin immunoreactivity (PA-IR) in the retinas of rats maintained on a 12:12 h light:dark cycle, or after being placed in constant darkness for 24–72 h. Retinas were harvested at zeitgeber and circadian times 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 h. PA-IR was found primarily in retinal amacrine cells of the AII subtype. In a light/dark cycle, PA-IR showed a clear rhythm, with a low near zeitgeber time (ZT) 10:00 h and a peak near ZT 18:00 h. The ratio of immunofluorescence intensities at these timepoints was >15-fold. When animals were kept in complete darkness for 1–3 days, the rhythm of PA-IR was still preserved, but was progressively reduced in amplitude. The rhythm of PA-IR inferred from immunohistochemical data was confirmed by Western blots. We conclude that PA-IR in the rat retina shows an underlying circadian rhythm that is enhanced by cyclic light. The regulation may involve translocation of the protein between cell compartments and/or new protein synthesis.This study was supported by an OTKA grant (T 34160), NIH grants NS 37919 (R.S.) and ET 03570, NSF grant IBN-96418886 (R.S.), and grants from the Helen Hoffritz Charitable Trust and Research to Prevent Blindness, Inc. R.G. was also in receipt of a János Bolyai fellowship     

Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein–based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia

Purpose: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). Methods: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. Results: Some patients had preexisting systemic IFN- CD4⁺ (1/10) and CD8⁺ (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN- CD8⁺ cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)–directed CD4⁺ response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. Conclusions: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients.