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R Braczkowski

Publications and source records attributed to R Braczkowski.

At least 19 recordsLinked to original sources

Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone tumors.

Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH) have been found in several human cancer cell lines. GHRH antagonists inhibit growth of various human cancers, including osteosarcomas and Ewing's sarcoma, xenografted into nude mice or cultured in vitro and their antiproliferative action could be mediated, in part, through these SV of GHRH receptors. In this study, we found mRNA for the SV(1) isoform of GHRH receptors in human osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted by the cells, as shown by the presence of GHRH-like immunoreactivity in the conditioned media of cell cultures. In proliferation studies in vitro, the growth of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of an autocrine stimulatory loop based on GHRH and SV(1) of GHRH receptors in human sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant bone tumors appear to be exerted through the SV(1) of GHRH receptors on tumoral cells.

Alternative Splicing↗

Decline of met-enkephalins concentration after interleukin-2 subcutaneous administration due to renal carcinoma.

The authors have described the connections between nervous and immune systems. Endogenous opioids are one of the factors linking both systems. Endogenous and exogenous opioids can modify the function of interferons, humoral factors, antibody production and lymphocytes' activation. Concurrently, some cytokines can modify the endogenous opioid system. The aim of this study was to asses whether the subcutaneous administration of IL-2 influences the Met-Enkephalins concentration in serum after IL-2 single administration due to renal cancer. The Met-Enk level was estimated with RIA method. The IL-2 single administration results in a significant decrease of Met-Enk in serum.

Adult↗

[Depression as a risk factor for cancer--is it still a hypothesis or a proven fact?].

The connection between depression and cancer has been described several times. These observations have been made on major depression and on other kinds of depression as well. It is possible that similar genetic defect may play an important role in the development of cancer and major depression. Disturbances in function of endocrine and immunological systems, which have been observed in depression, can be the risk factor for cancer. Large epidemiological research showed that in persons with depression increased risk of cancer diseases, but not every research confirm it. Large disagreement of research results don't permit of sure answer, but the hypothesis is still possible and require incessant research. Development of research methods, particularly a new domain called molecular epidemiology give hope for more precise future answer.

Antibody Formation↗

Transient increase of plasma interleukin-6 after infusion of recombinant tumor necrosis factor alpha in advanced cancer patients.

Tumor Necrosis Factor alpha administered in the therapy of advanced cancer influences certain hormones and cytokines secretion. In turn, these also modulate the biological activity of Tumor Necrosis Factor alpha. It has been shown in several studies that the cytokine Interleukin -6 (IL)-6 is produced in response to various hormones and other cytokines eg. Tumor Necrosis Factor (TNF alpha). In our study we focused on the Interleukin-6 (IL-6) secretion in response to TNF alpha administration in 12 patients undergoing TNF alpha biotherapy due to advanced neoplastic disease. Plasma IL-6 was estimated prior and at various time points (2, 3, 5 a,d 12 hours) after TNF alpha intravenous infusion. IL-6 level was estimated with ELISA method. In conclusion, we suggest the stimulating influence of hrec TNF alpha administered as therapy for advanced cancer on IL-6 secretion.

Adult↗

Genetic testing for breast cancer susceptibility: Polish women's attitudes.

The aim of our study was to assess Polish women's attitudes and possible acceptance of genetic tests for breast cancer susceptibility. The research was carried out in 1995-1996 and enrolled 200 women of different age, education and professional status who were asked to answer the questions included in a questionnaire. We estimate the percentage of women presenting different attitudes towards breast cancer genetic testing: 77% of women accepted genetic tests for breast cancer (BRCA) and 48% of women accepted informing their close relatives of the genetic tests results.

Adolescent↗

Possible biological indicators of the response to recombinant tumour necrosis factor alpha in patients with advanced neoplasms.

Tumour Necrosis Factor alpha (TNF alpha) immunotherapy, in addition to that of Interleukin-2 immunotherapy, represents one of the most promising biotherapies for human neoplasms. In order to identify immunological parameters of prognostic value we studied changes in immune response during first cycle of treatment with hree TNF alpha. The study included 21 locally advanced or metastatic solid tumor patients (M/F:12/9 median age: 57 years, range 38-65) for whom no other standard therapy was available. TNF alpha was administered before midday by a 20-minute intravenous infusion at a dose of 75 microg/day for 5 consecutive days corresponding to one cycle. In the absence of progression two further cycles of TNF alpha were given at 14 day intervals during which the dose was increased by 50 microg/day i.e. 2nd cycle- 100 microg/day, 3rd cycle- 150 microg/day. Of 21 patients evaluated for both clinical and immunological responses, 4 had complete response and 4 patients had partial response. The present study suggests that TNF alpha biotherapy is not associated with an increase in the number of circulating lymphocytes. Regarding lymphocyte subtype, a slight increase has been observed as far as T lymphocyte subsets are concerned. The CD4/CD8 ratio in cancer patients treated with hree TNF alpha showed significantly lower values than before treatment. On the basis of in vitro experiments an increase in NK cell activation in tissue culture, in addition to an increase of LAK cells, was observed.

Adult↗

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland.

Three different novel BRCA1 mutations, five independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.

Adolescent↗

Prevention of cytokine-induced hypotension in cancer patients by the pineal hormone melatonin.

Hypotension is a frequent side-effect of cancer biotherapies with cytokines. Cytokine-induced hypotension would mainly depend on the stimulation of nitric oxide (NO) production, which represents the most effective endogenous vasodilator. Moreover, it has been proven that both biological activity and toxicity of cytokines are influenced by the psychoneuroendocrine system, in particular by the pineal hormone melatonin. To investigate the possible modulatory effect of melatonin on cytokine cardiovascular toxicity, we evaluated the influence of a concomitant melatonin administration on interleukin-2(IL-2)- and tumour-necrosis-factor-alpha(TNF)-induced hypotension in advanced cancer patients. The study included 116 patients with advanced solid tumour, for whom no effective standard anticancer therapy was available, who underwent cancer biotherapy with IL-2 (3 x 10(6) IU/ day s.c. every day, 6 days/week for 4 weeks) or with TNF (0.75 mg/day i.v. for 5 days) as compassionate treatment for their disease. Patients were randomized to be treated with or without a concomitant melatonin administration (40 mg/day orally in the evening, starting 7 days prior to cytokine injection). The occurrence of hypotension was significantly less frequent in patients concomitantly treated by melatonin than in those who received the cytokine alone, during either IL-2: or TNF immunotherapy (IL-2; 11/45 versus 2/46, P < 0.05; TNF: 10/23 versus 1/12, P < 0.01). This study shows that melatonin may prevent hypotension occurring during cancer immunotherapy with IL-2 or TNF. Since the pineal hormone has appeared to inhibit the activity of NO synthase from the endothelial cells, we suggest that melatonin may prevent cytokine-induced hypotension by inhibiting NO production, which plays an essential role in inducing hypotension during IL-2 and TNF biotherapies.

Administration, Oral↗

[Cardiotoxic effect of the herec-TNF alpha preparation given intravenously to patients with advanced neoplasms].

The group of 17 patients with advanced neoplastic disease has been treated with combined therapy with herec TNF alpha in association with IFN alpha and 5-Fu, the cardiotoxic effect of herec TNF alpha administration has been observed. The 30 minutes intravenous infusion of herec TNF alpha caused statistically significant increase of heart rate (in comparison to the previous value). There was also observed the decreasing of blood pressure value (about approximately 20-30 mmHg), spontaneously disappeared after the infusion ending. Rarely, the heart rhythm disturbances i.e.: ventricle extrasystoles in II, III, IV in Lown score have been observed. In 2 cases there was additional pharmacological treatment. In the rest of the patients the early cardiotoxic effects have not been associated with haemodynamic disturbances.

Adult↗

[A case of recurrent untreated non-hodgkin's lymphoma localized in the nasopharynx and maxillary sinuses after a 10-year remission].

We present the case of non-Hodgkin lymphoma (lymphoma malignum lymphocyticum) localised in nasal cavity and paranasal sinus (maxillary sinus). The patient suffered from weakness, fever and rhinorrhoea. We applied the chemotherapy (grade IV degrees) in COP, achieving partial remission. We also place emphasis on 10-year period of idiopathic neoplasm remission since the establishment of diagnosis.

Adult↗

[Influence of treatment using recombinant tumor necrosis factor alpha (hrec TNF alpha) on circadian rhythm of cortisol secretion in patients with advanced neoplastic disease].

UNLABELLED: Tumor Necrosis Factor alpha is one of cytokines administered in immunotherapy of advanced neoplastic disease. Its action is exerted through immune endocrine and central nervous systems. The purpose of this study was to assess the influence of hrec TNF alpha administration in patients with advanced neoplasms on the level of cortisol in serum and its circadian rhythm. Serum cortisol was determined several times a day before and just after hrec TNF alpha first immunotherapeutic cycle. The results of the investigation were analysed with the Cosinor test. Serum concentration of hormone was determined using radioimmunoassay method. The results of this study showed the decreasing influence of hrec TNF alpha administration on cortisol secretion by adrenals with no disturbances in that circadian rhythm. IN CONCLUSION: It might be possible that some side effects of hrec TNF alpha administration are connected with the decreasing cortisol level.

Adult↗