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Biomedical subjects

B Zubelewicz

Publications and source records attributed to B Zubelewicz.

At least 19 recordsLinked to original sources
PubMed2004

Genetic disregulation of gene coding tumor necrosis factor alpha receptors (TNFalpha Rs) in colorectal cancer cells.

The expression of TNF ligand by malignant cells might be a mechanism for tumour immune escape. Genetic disregulation of gene coding TNF receptors was observed in neoplastic disease by an increased number of receptors on tumour cells and ligand-receptor activity. It might cause tumour proliferation and metastatic potential. Structure of TNF receptors influences TNF activity in vivo and structure of TNF R2 gene may suggest post-transcription modification based on alternative splicing. The aim of the study was to analyse the expression of gene coding TNF receptors R2 and R2/R7 (without exon 7) by estimation of mRNA expression of colorectal cancer cells in comparison with surrounding tissue free from neoplastic infiltration and searched for differently spliced TNFalphaR2/R7 isoforms. The study included fifty four patients with histopathologically confirmed adenocarcinoma (Stage III according to the AJC TNM Classification). Tissue samples removed from the tumour region were obtained from colorectal cancer patients undergoing surgical treatment. The samples were divided into two parts. The first one--was routinely examined histopathologically, the second one--was used for RNA extraction and the number of TNF and its receptors mRNA copies were subsequently quantified. The TNF and TNFRII genes expression were estimated based on the number of mRNA copies on 1 microg total RNA. The presence of TNFR2 and TNFR2/R7 isoforms in tumour, normal and metastatic cells was observed. The highest number of mRNA TNF copies and over expressed TNF genes were investigated and significantly noticed in metastatic cells (lymph nodes). The decreased number of TNFR2/R7 mRNA copies in metastatic lymph nodes secondarily influenced the decreased TNF soluble receptors' concentration. In conclusion, the genetic disregulation observed in neoplastic disease usually concerns dysfunction of cytokines receptor genes.

Adenocarcinoma↗
PubMed2003

Circadian fluctuations of melatonin, tumor necrosis factor-alpha and its soluble receptors in the circulation of patients with advanced gastrointestinal cancer.

The objective of the study was to investigate the dynamic changes of melatonin (MLT), tumor necrosis factor alpha (TNFalpha), soluble TNFalpha receptors ( type I and type II) in serum of advanced cancer patients during 24 hours. The examined group consisted of 42 patients suffering from advanced gastrointestinal neoplasms (colorectal, gastric and pancreatic cancer). Blood samples were collected 6 times a day (8 a.m., 2 p.m., 6 p.m., 10 p.m., 2 a.m., and again 8 a.m.) as well as in healthy controls. Serum levels of TNFalpha and both its receptors were measured using ELISA type and the radioimmunoassay method was used to assess MLT levels. The circadian rhythm of MLT was altered because MLT reached its peak level at 8.50 a.m. with 5 hours delay in respect to average peak time in healthy humans. The presence of circadian rhythm of TNFalpha was proved (acrophase-1.40 a.m.), and no diurnal rhythm of soluble TNF receptors was observed. The concentration of soluble type I (p-55) receptor was distinctly lower than soluble type II (p-75). The peak of soluble type I receptor value appeared at 10.00 p.m. while the type II receptor reached its minimum level at the same time. Although there was no statistical correlation between the receptor concentrations, the shapes of both curves remained inversely proportional. The present results may suggest the presence of complex self-regulation mechanisms between the neuroendocrine system and the cytokine network in advanced gastrointestinal cancer patients.

Adult↗
PubMed2000

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↗
PubMed2000

[Soluble tumor necrosis factor receptors--their properties and role in diagnosis and therapy of acute and chronic diseases].

The review presents the properties and significance of soluble forms of tumor necrosis factor-alpha receptors in physiology and pathology of human organism. Special attention was turned to the possibility of practical application of those forms of the receptors in the therapy of diseases caused by excessive activity of TNF-alpha. The significance of the soluble receptors as prognostic factors of disease progression and outcome was stressed.

Acute Disease↗
PubMed2000

Central single and chronic administration of morphine stimulates corticosterone and interleukin (IL)-6 in adjuvant-induced arthritis.

Adjuvant-induced arthritis (AA) in the rat is a chronic inflammatory stress in which circulating corticosterone and interleukin (IL)-6 levels are elevated. In addition, there are profound neuroendocrine changes associated with the development of hind-paw inflammation which have major implications for the ability of the rat to respond to stress. Central injection of morphine is able to increase plasma corticosterone and circulating IL-6 concentration in control animals. In present study we have determined the effects of a single and repeated injection of morphine into the lateral ventricle of control and AA animals on plasma corticosterone, circulating IL-6 levels and course of hind-paw inflammation in AA rats. In the present study we found a sustained increase in plasma corticosterone both after single and repeated injection of morphine in control and AA rats and an increase of the level of circulating IL-6 in AA rats after repeated injection of morphine. These data suggest that alternative systems distinct from Athose activated in response to acute stress are activated by morphine in the AA animals. The similarity with the sustained increase in corticosterone following LPS injection suggest that central opiates may be involved in mediating HPA axis and cytokines response to inflammatory stress.

Analgesics, Opioid↗
PubMed1999

Central LPS-induced c-fos expression in the PVN and the A1/A2 brainstem noradrenergic cell groups is altered by adrenalectomy.

The A1 and A2 brainstem noradrenergic cell groups project to the hypothalamic paraventricular nucleus (PVN), which is involved in integrating the stress response. Bi-directional communication between the brain and immune system is well established, with both neuroendocrine and immune responses being activated by lipopolysaccharide (LPS). The mechanisms underlying such activation and differences between alternative routes of administration remain unclear. We examined activation of the PVN and A1/A2 cell groups, by assessing c-fos mRNA, or counting Fos-positive neurons in either the PVN or in brainstem A1/A2 cell groups 3 h after intracerebroventricular (i.c.v.) LPS, in control and adrenalectomized (ADX) rats. We also measured corticotropin-releasing hormone (CRH) mRNA in the PVN, and plasma corticosterone (CORT) levels. A group of ADX/CORT-replaced animals received i.c.v. LPS, and CRH mRNA and Fos peptide in the PVN were analysed. ADX increased CRH mRNA in the PVN, as did LPS, but no enhancement of this response was seen in LPS/ADX animals. C-fos mRNA also increased in both the PVN and the A2 cell group following LPS, but this response was potentiated by ADX. Fos peptide-containing cells increased in the PVN and A2 following LPS, and this change was amplified by ADX. Only 11.25% of Fos was found in DBH-positive (putative noradrenergic) neurons, suggesting activation of neurons containing other transmitters. ADX/LPS/CORT animals showed numbers of Fos neurons in the brainstem, and CRH mRNA levels in the PVN which were comparable to intact/LPS animals. Central LPS activates the hypothalamo-pituitary-adrenal axis, a process mediated partly by brainstem noradrenergic neurons, suggesting the involvement of afferent/efferent pathways within the brain. Peripheral administration of LPS involves activation of vagal inputs leading to the nucleus tractus solitarius. We suggest that centrally administered LPS activates the A2 cell group by a mechanism independent of the vagus. In the absence of CORT, despite the lack of a CRH mRNA response, an exaggerated c-fos and peptide response to LPS is observed, which is reversed following CORT pretreatment.

Adrenalectomy↗
PubMed1999

The estimation of endogenous tumor necrosis factor alpha and cortisol levels in serum in advanced neoplasm.

The immune reaction mediators--cytokines may play an important role in central nervous system function and influence the neuroendocrine system. The aim of the study was to assess the hypothesis of a possible correlation between endogenous TNF-alpha and glucocorticoids secretion in advanced neoplasm. Thirty patients (17 males and 13 females) with advanced neoplasm were enrolled in the study. The levels of TNF-alpha were measured with ELISA type test and cortisol levels were estimated by RIA method. The blood samples were collected 6 times during 24-hours for TNF and 6 times a day for cortisol. Twenty healthy volunteers were studied in parallel. Both TNF-alpha and cortisol levels revealed the presence of circadian rhythm in examined patients. The levels of TNF-alpha were very high and achieved the peak value about midnight (acrophase-01.40). Cortisol peak was found typically at 08.08. The fluctuations of examined molecules showed regular patterns. TNF-alpha levels markedly decreased together with the increase of cortisol and rose when cortisol concentration in serum was low. Although the correlation was not confirmed by Spearman correlation rank the shapes displayed by both curves may suggest the presence of neuroendocrine feed-back loop between corticosteroids and TNF-alpha in advanced cancer.

Aged↗
PubMed1999

[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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1996

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↗
PubMed1996

Is there a role for melatonin in the treatment of neoplastic cachexia?

It is known that neoplastic cachexia shows metabolic characteristics different from other common causes of malnutrition, and that it is mainly due to an abnormal secretion of TNF, whose levels are often high in patients with advanced neoplasia. Previous clinical studies have suggested that the pineal hormone melatonin (MLT), which plays an essential role in the neuroendocrine regulation of biological systems, may improve the clinical status of advanced cancer patients and inhibit TNF secretion. To investigate the relationship between MLT, TNF and cancer-related weight loss, 100 untreatable metastatic solid tumour patients entered this study to receive either supportive care alone, or supportive care plus MLT (20 mg/day orally in the evening). Patients were observed for 3 months, and were considered evaluable when they were observed for at least 2 months. There were 86 evaluable patients, the other 14 patients having died from rapid progression of disease. The per cent of weight loss greater than 10% was significantly higher in patients treated by supportive care alone than in those concomitantly treated by MLT, with no difference in food intake (P < 0.01). Mean serum levels of TNF progressively increased in the supportive care group, but to levels that were not significantly different from pretreatment values. In contrast, TNF mean concentrations significantly decreased (P < 0.05) in patients concomitantly treated by MLT. These results suggest that the pineal hormone MLT may be effective in the treatment of the neoplastic cachexia by decreasing TNF blood concentrations.

Adult↗
PubMed1996

[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↗
PubMed1996

[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↗