Search

W niniejszej pracy przedstawiono uaktualnione zalecenia grupy ekspertow Polskiej Sieci Guzow Neuroendokrynnych dotyczące zasad postepowania w nowotworach neuroendokrynnych zolądka i dwunastnicy z uwzglednieniem gastrinoma . Omowiono epidemiologie, patogeneze i obraz kliniczny tych nowotworow. Przedstawiono zalecenia dotyczące zasad postepowania diagnostycznego, z uwzglednieniem diagnostyki biochemicznej, histopatologicznej oraz lokalizacyjnej. Uwzgledniono takze zasady postepowania terapeutycznego, w tym leczenie endoskopowe i chirurgiczne, oraz omowiono mozliwości leczenia farmakologicznego i radioizotopowego. Przedstawiono takze zalecenia odnośnie monitorowania chorych z NEN zolądka, dwunastnicy z uwzglednieniem gastrinoma .

Nowotwory neuroendokrynne (NENs) jelita grubego stanowią 20% wszystkich nowotworow neuroendokrynnych. Najczestszą ich lokalizacją jest odbytnica. Nowotwory neuroendokrynne jelita grubego są wykrywane coraz cześciej i liczba ta bedzie wzrastac z uwagi na powszechnośc wykonywania kolonoskopii, w tym badan przesiewowych oraz usuwanie wykrytych zmian. W pracy przedstawiono aktualne zalecenia dotyczące diagnostyki i terapii NEN jelita grubego, z uwzglednieniem diagnostyki biochemicznej, patomorfologicznej, nowych technik obrazowania oraz leczenia endoskopowego, chirurgicznego, farmakologicznego i radioizotopowego. Omowiono takze epidemiologie, charakterystyke kliniczną i monitorowanie leczenia.

Adiponectin, a peptide hormone secreted from the adipose tissue, has anti-diabetic, anti-atherogenic, and anti-inflammatory properties and is also involved in the regulation of angiogenesis. However, there are discrepancies among the results of the published data regarding its pro- or anti-angiogenic properties. The aim of our study was to examine the direct effect of various adiponectin concentrations applied separately or in combination with thalidomide on the growth of the murine endothelial cell line HECa 10 in 24- and 72-hour cell cultures.We used immortalized murine endothelial cell line received from endothelial cells of the mouse peripheral lymph node. The effect of adiponectin was examined at concentrations from 10(-5) to 10(-12)M. Thalidomide was used at 10(-3)M concentration. The growth of HECa10 cells was assessed by the colorimetric Mosmann method.We found that adiponectin inhibited the growth of HECa 10 line at all examined concentrations in the 24-hour culture, with moderate potency. There were no dose- or time-response effects. In the 72-hour cell culture, adiponectin inhibited the growth with the same or weaker potency and we did not observe its inhibitory effect at 10(-12)M concentration. There was no beneficial interaction between adiponectin and thalidomide. In this study, however, thalidomide alone did not cause any inhibitory effect on this cell line.The obtained data show that adiponectin inhibits endothelial cell growth and may participate in angiogenesis regulation as an endogenous antiangiogenic factor.

The poor efficacy of reference chemotherapy (fluorouracil -FU) in colon cancer has resulted in a constant search for agents which could augment the action of FU. Epidemiological data, such as the decreased risk of colorectal cancer among menopausal women receiving hormonal replacement therapy, indicate the role of oestrogen in the pathogenesis of this disease. The differences between normal and neoplastic colon cells in the expression of oestrogen receptor beta (ERbeta) could confirm this association. However, the direct influence of oestrogen or tamoxifen (SERM, selective oestrogen receptor modulator) on colon cancer growth has rarely been studied. The aim of the present study was to examine the direct effects of various concentrations of oestradiol and tamoxifen (10(-4) to 10(-12) M), applied alone or together with FU, on the growth of murine Colon 38 cancer in vitro as assessed by three colorimetric methods: Mosmann's method, incorporation of BrdU into cell nuclei and the TUNEL method. At high concentrations oestradiol and tamoxifen decreased the cancer growth in a dose- and time-dependent manner (the Mosmann and BrdU methods) and at some concentrations augmented the cytotoxic action of FU (Mosmann's method). Tamoxifen exerted a very early and potent inhibitory effect, inducing even total cancer growth inhibition at the concentration of 10(-4) M (the Mosmann and BrdU methods). All the substances studied at different concentrations and at different incubation time points increased the apoptosis of tumour cells (the TUNEL method). The results indicate that oestradiol and tamoxifen inhibit Colon 38 cancer growth and increase the cytotoxic effect of FU, which confirms the role of sex steroids in colon carcinogenesis and even suggests new therapeutic schemes.

Epidemiological studies underline the fact that obesity represents a significant risk factor for the development of several cancers, one of which is cancer of the colon. Moreover, multiple recent data indicate that some adipose tissue-derived hormones may influence the growth of malignant cells. Leptin, the product of the ob gene, is one of these. However, the evidence from research is still contradictory regarding the role of leptin in colon cancer. The aim of our study was to examine the direct effect of leptin at various concentrations (from 10(-5) to 10(-12) M) when applied alone or jointly with fluorouracil (the classical cytotoxic drug for colon cancer) at two concentrations (0.25 mg/ml and 2.5 mg/ml) on the growth of murine Colon 38 cancer cells in vitro.Colon 38 cancer cells were preincubated in RPMI 1640 medium supplemented with foetal calf serum for 24 hours. The cells were then cultured for a further 72 hours in the presence of various concentrations of the substances under examination, applied either alone or jointly. The growth of the Colon 38 cell line was assessed by a colorimetric kit based on the modified Mosmann method.We found that leptin increased the growth of murine Colon 38 cancer at concentrations of 10(-6), 10(-7) M and 10(-10), 10(-11), 10(-12) M. Its stimulatory effect was fairly slight, with an increase in cancer growth of 5% to 15% as compared to controls. As we expected, fluorouracil at both the concentrations examined inhibited the growth of Colon 38 cancer maximally up to 28% (2.5 mg/ml) and 34% (0.25 mg/ml) of controls, with a stronger effect obtained from higher doses. Leptin did not modulate the cytotoxic effect of fluorouracil applied at the higher concentration (2.5 mg/ml) but, unexpectedly, at concentrations of 1(-9) and 10(-10) M it heightened the cytotoxic effect of fluorouracil given at a lower concentration (0.25 mg/ml).These data indicate that leptin is involved in the regulation of colon cancer growth and it may even heighten the cytotoxic effect of fluorouracil.

The role of gastrins and their receptors in the pathogenesis of colon cancer has been discussed for many years but it still remains unresolved. Although fluorouracil (FU) remains to be reference chemotherapy for colon cancer, its efficacy is unsatisfactory. Recently, we have shown a synergistic effect of proglumide (a non-selective blocker of cholecystokinin-gastrin receptors) applied together with FU, on the proliferation and apoptosis of transplantable Colon 38 cancer cells in vivo. The aim of this study was to examine direct effects of proglumide (10(-5)-10(-10) M) applied either alone or together with FU (0.25, 2.5 and 25 microg/ml) on the proliferation of murine Colon 38 cancer cells in vitro. Cell proliferation was assessed by the modified colorimetric Mosmann method. Proglumide inhibited the proliferation of Colon 38 cells at the concentrations of 10(-6), 10(-8) and 10(-10) M. FU inhibited the proliferation of cancer cells in all studied concentrations, exerting the most profound antiproliferative effect at the concentrations of 2.5 and 25 microg/ml. Thus, the former concentration was chosen to study its interactions with proglumide. Proglumide applied together with FU exerted a synergistic effect on the inhibition of proliferation of Colon 38 cells at 10(-8), 10(-9), 10(-10) M concentrations. The most profound inhibitory effect was observed in the group incubated with FU and 10(-10) M of proglumide. The obtained results indicate a possibility of new therapeutic options for colon cancer, but further studies are needed to elucidate, if the synergistic effect of FU and proglumide occurs also in the colon cancer in humans.

Growth Hormone-Releasing Hormone (GHRH) is the main factor, which regulates GH secretion and somatotrope proliferation. However, its chronic effect on anterior pituitary gland is still unknown. It is known that excessive GHRH secretion in patients with gastroenteropancreatic tumors secreting GHRH results in acromegaly and somatotrope hyperplasia. In mice transgenic for GHRH somatotrope tumors develop. Thus, the aim of this paper was to examine the effect of GHRH chronic administration on somatotrope secretion, their percentage and cell proliferation in anterior pituitary gland in rats. The experiment was performed on male Fischer 344 rats weighing 200+/-20 g. The animals were divided into two groups: group I-controls (13 rats) received solvent for GHRH (5% ethanol in demineralized water); group II (10 rats) received GHRH (Growth Hormone Releasing Factor, fragment 1-29 amide) at a dose of 5 microg/day. The substances were given for 1 month via osmotic pump (ALZET), which were implanted subcutaneously in the dorsal region under ketamin anesthesia. After 4 weeks all rats were decapitated and the blood was collected. In the microscopic preparations of anterior pituitary gland the morphology of pituitary (Herlant staining) and the percentage of somatotrope cells and proliferation index based on PCNA staining were assessed. It was found that the chronic treatment with GHRH caused a statistically significant increase in serum rGH concentration and in percentage of somatotropes, but did not change proliferation index and did not induce pathological changes in the morphology of the anterior pituitary gland when compared to the control group. Summing up, monthly GHRH administration did not induce somatotrope adenomas but it caused serum GH level elevation, what seems to depend partially on the increase of somatotrope number.

Pituitary adenomas are common benign neoplasms, accounting for approximately 15% of intracranial tumors. In systematic autopsy, pituitary tumors are found in 25%, of the population, but only one-third of these tumors give rise to clinical manifestations. Why most of these neoplasms remain undiagnosed and pituitary carcinomas are extremely rare? The progress in the studies concerning pituitary tumorigenesis is rather slow and, due to several limitations, including the anatomic inaccessibility of human pituitary gland, the lack of functional human cell lines in culture and the discrepancies between human and animal pituitary oncogenesis (in rodents pituitary hyperplasia is a prerequisite for adenoma development). In humans, the majority of pituitary tumors are monoclonal in origin and derived from single mutated pituicyte, rarely hyperplasia is a prerequisite for adenoma formation. As in the case of other tumors, activating mutations in oncogenes (GNAS1, PTTG) and inactivating mutations in tumor suppressor genes (MEN1, CNC1) lead to pituitary tumors development. However, mutations in classic oncogenes are very rarely associated with these tumors. Moreover, the important role of some hypothalamic hormones, peripheral hormones and their receptors (e.g. GHRH, dopamine D2 receptor, PRL receptor, estrogens, thyroid hormone receptor) and growth factors (e.g. FGF, EGF, TGF) is postulated and partially proved in promotion of pituitary tumorigenesis. Further studies are required to determine which of these events are truly primary changes in pituitary tumorigenesis, what may allow development of gene therapy.