[en] Background and purpose: Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines. Material and methods: Calreticulin (CRT) exposure was detected on cancer cell surface. ATP, HMGB1 and cytokines were measured in culture supernatants. Maturation marker CD83 surface exposure was determined on DCs after co-incubation with irradiated tumor cells. Results: There was no increase in DAMPs and cytokine profiles after radiation treatment and no difference between HPV+ and HPV− cell lines. The HPV/p16-positive SCC90 cells showed a trend for increased total CRT, HMGB1, and number of cytokines compared to all other cell lines. None of the irradiated cancer cell lines could affect DC maturation. Conclusions: Radiation treatment did not increase immunogenicity of HNSCC cell lines assessed by membrane CRT, ATP, HMGB1, cytokines production, and by activation of immature DCs. There was no difference between HPV-positive and HPV-negative cell lines.

[en] The effect of Paclitaxel (PAC), Epirubicin (EPR) and Tamoxifen (TAM) on ''3H-thymidine labelling index (''3H-TdR LI) of Ehrlich ascites tumor cells (EAT) was investigated in cultured. In the present study, an estrogen receptor positive ER(+) hyper diploid cell lines were studied. We used optimum doses of PAC, EPR and TAM (12 mg/ml, 12 mg/ml and 2 mg/ml, respectively). Cells were treated with these doses for 0, 4, 8, 16 and 32 hours. At the end of these periods, both control and treated cells were labelled for 5 mCi/ml 3H-thymidine for 30 minutes. The results showed that inhibition of DNA synthesis in cultured EAT cells were increased in the combined treatment of two drugs when compared to the treatment of a single drug (p<0.01). In the treatment of three drugs, however, this effect reached a maximum (p<0.001). As a result, PAC+EPR+TAM treatment's had a maximum synergistic effect at 4 hours treatment

[en] In this paper, I will not describe in detail the biochemical, biological, or oncogenetic aspects of tumor makers, but will limit my discussion to the clinical applications of tumor markers, and, in some instances, comment on some specific aspects or methodology. The biological characteristics of tumor makers can be observed in the differences between normal and cancerous cells. For clinical diagnostics, the improtant question is whether or not we can detect these changes by in vitro tests. By immunological means, we are able to detect changes on cell surfaces by measuring either differentiated antigens or cell specific antigens. (Author)

[en] Indolent B-cell lymphomas comprise a heterogeneous group of diseases. For patients with limited disease is local radiotherapy the treatment of choice.Watch and wait is the standard of care for patients with asymptomatic advanced stage disease. Standard first line treatment for symptomatic patients is chemo immunotherapy. The recent rediscovery of the „old“ chemotherapeutic agent bendamustin enhanced therapeutic options in indolent B-cell lymphomas. Thanks its favourable therapeutic index and effectiveness it is increasingly used in the in the first line and relapse setting as well. In patients with follicular lymphoma, the maintenance with rituximab after effective chemo immunotherapy is indicated. Earlier or later the relapse occurs in indolent lymphomas. It is the reason to have a wide variety of treatment options. In the last years we witness marked progress in the new drugs development. The new promising drugs are novel monoclonal antibodies, proteasome inhibitors, novel agents targeting a certain level of B-cell receptor signaling pathways, bcl-2 inhibitors or immunomodulatory agents. Novel agents may change our treatment approach to indolent lymphomas in the near future. (author)

[en] Relapsed testicular germ cell tumors (GCTs) can potentially be cured with salvage chemotherapy. The two main salvage treatment options are conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT). HDCT combined with peripheral blood stem cell transplant (PBSCT) may offer a higher rate of durable responses compared to CDCT. This review discusses studies reporting outcomes of salvage HDCT in relapsed GCTs. The most consistent results were seen with HDCT involving two cycles of etoposide and carboplatin, or three cycles of the TICE regimen (paclitaxel, ifosfamide, carboplatin, and etoposide). Using these regimens, sustained cure rates of 50-66% have been reported in phase I, phase II, and retrospective studies over the past twenty years. For patients with cisplatin-resistant disease, cure rates range from 30% to 45%. Two phase III randomized studies, which had certain limitations, failed to show a survival benefit for HDCT. As a result, salvage treatment remains a topic of debate. Both HDCT with PBSCT and CDCT are recommended treatment options for relapsed GCTs. Consistently reported cure rates from phase I, phase II, and large retrospective studies support the use of HDCT by an experienced oncology team. (author)

[en] The possibilities to enhance the lethal effect of ionizing radiation on hypoxic cells by electron-affinic compounds have stimulated the investigations for finding new chemicals with radiobiological and pharmacological features as adequate as possible. On the other hand, the experimental studies and clinical trials had shown that the aerobic toxicity seems to be the major limiting factor in the use of large doses of radiosensitizers required to achieve significant therapeutic efficiency. The investigations in the present paper were attempted to join these two main directions of research and comprised the syntheses of new nitroheterocyclic compounds with potential radiosensitization properties and the knowledge of biochemical alterations involved in the producing of aerobic toxicity of radiosensitizers aiming to find practical solutions to enhance the efficiency of radiotherapy. Several newly synthesized compounds were tested for their radiosensitizing effect. The experiments carried out on hypoxic cells V 79 showed that only 1-(hydroxyethyl-2'-phosphate)-2-methyl-5-nitroimidazole, dipotassium salt displayed an enhancement ratio of 1.17 (at 8 mM), but lower than in case of parent compound, metronidazole (enhancement ratio = 1.53). It was shown that hypoxic cell radiosensitizers interfere with the cellular energy metabolism. These interferences were found dependent on the electron affinity of drugs. In addition, those radiosensitizers producing a decrease in oxygen consumption caused a supplementary oxygenation of both normal and tumour tissues. It is concluded that the improvement of therapeutic efficiency of radiosensitizers by reducing their aerobic toxicity might be achieved by diminishing their effects on the energy metabolism or by the stimulation of this metabolism and restoration of tissue redox equilibrium

[en] Response of the Fib/T tumor to equal fractions of radiation, spaced by an interval of 24h, was determined in tumor-bearing mice that were pretreated either with 8% oxygen for 48h or with air. Increase in tumor cell kill occurred in the group of animals that received low oxygen pretreatment. Tumor cell kill was further and significantly increased if mice were retained in the low oxygen environment for the 24h interval between radiation fractions. Possible explanations for these findings are proposed and discussed. The effect of 48h 8% exposure in modifying the response of the Fib/T tumor to 2 fractions of radiation, both delivered in hyperbaric oxygen, was also investigated. The low oxygen pretreatment did not significantly alter tumor response to radiation given under conditions of hyperbaric oxygenation. 17 refs.; 3 figs.; 2 tabs

[en] The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness

[en] Chemotherapy based on fluoro pyrimidines and irinotecan or oxaliplatine has been the cornerstone of treatment patients with metastatic colorectal cancer (mCRC) for several decades. Despite the introduction of new drugs targeting the vascular endothelial growth factor or epidermal growth factor receptor survival and disease control remains poor. The median survival of patients has improved from one year to more than three years due to the introduction of target therapy. The optimal combination and sequence of treatment is unknown for now, but it should be very carefully chosen based on the current available data. The data show that patients whose primary tumors originate on the left side of the colon survive significantly longer than those whose tumors originate on the right side. Early tumor shrinkage (ETS) and depth of response (DpR) predict overall survival (OS) in first-line trials of chemotherapy ± anti-EGFR monoclonal antibodies in metastatic colorectal cancer. (author)

[en] Enteral feeding provides physiologic, metabolic, safety, and cost benefits over parenteral nutrition. There are various ways enteral nutritional is administered and scheduled. The method of administration must be individualized to each patient's specific needs. Enteral nutrition is not only the supply of exogenous substrates and to prevent depletion of endogenous sources. Today the enteral nutrition becomes part of a therapeutic strategy to influence the severity of the disease to affect the function of GIT, and to modulate immune responses of the gut and the whole organism. Early enteral nutrition in the postoperative period reduces the risk of infectious complications. (author)