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EN
Melanomas of the mucous membranes of airway tract constitute around 1% of the total melanomas of head and neck. The most common site of the tumor are the nasal and paranasal sinuses but melanomas of the oral cavity are described too. The location of malignant melanoma in the eustachian tube is very rare. We found five cases of this disease in the literature. In our article we present a 53-year-old woman with progressive left aural fullness and hearing impairment for two months. Clinical examination found left middle ear effusion. The nasopharyngoscopy revealed a bluish red, friable and granulomatous tumor occupying the whole pharyngeal orifice of the left auditory tube. The biopsy speciment was taken which established the diagnosis. Because of localization and spread of the melanoma we had a low opinion of surgical treatment and radiotherapy was recommended. The patient was under constant laryngologic and oncological observation. We did not notice the local recurrence of melanoma. She died two years after making the diagnosis because of the neoplasm dissemination.
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2005
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vol. 52
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issue 4
875-879
EN
Angioarrestin is a recently described anti-angiogenic protein whose expression is down-regulated in solid tumours of various origins. It has a sequence identical to angiopoietin related protein-1. In this study we investigated anti-tumour properties of angioarrestin in B16 (F10) melanoma tumour model. We constructed an expression vector encoding human angioarrestin under the control of EF-1α promoter. This vector was transferred to B16 (F10) cells and recombinant angioarrestin secreted from the transfected cells was tested for anti-angiogenic activity using endothelial cell proliferation assay. Finally, mice were injected subcutaneously with cells that had been transfected with either angioarrestin-encoding vector or empty vector and tumor growth was compared. The obtained recombinant angioarrestin inhibited proliferation of bovine aortic endothelial cells. Tumours derived from an angioarrestin-secreting B16 (F10) cell clone grew in vivo more slowly than tumours derived from a cell clone transfected with empty vector. These data show, to our knowledge for the first time, that angioarrestin can inhibit primary melanoma tumour growth.
EN
Spectroscopic, photochemical and biological properties of indocyanine green (ICG) are presented. Light over 800 nm is effectively absorbed by ICG. This property as well as photochemical behaviour of ICG make it a very suitable dye for photodynamic treatment of melanoma cells. Cytotoxicity of ICG itself and the effect of photodynamic therapy (PDT) were evaluated by following the growth of human (SKMEL 188) and mouse (S91) melanoma cells. The surviving fraction of the cells irradiated (λex = 830 nm) vs non-irradiated, treated with the same dose of ICG, is significantly decreased (5- to 10-fold). These results show that ICG is a very promising dye for photodynamic therapy of melanomas.
EN
A major progress has been made in the systemic treatment of advanced melanoma over the last few years. Targeted therapy has proven highly active, which is reflected in the response rate as well as progression-free survival and overall survival times. The paper aims to summarize the current knowledge on the available BRAF and MEK inhibitors.
EN
Ipilimumab, an anticancer drug, is an anti-CTLA4 monoclonal antibody. It is used in treatment of disseminated melanoma. Therapy is associated with high risk of complications. One of the most serious, although one of the rarest is perforation of gastrointestinal tract. In this case report we describe a 52-year old male, with disseminated melanoma with unknown starting point, treated with anti- CTLA4 monoclonal antibody. After 3rd dose of drug administration, bloody diarrhea and acute abdominal pain occurred as a symptom of gastrointestinal perforation. A single perforation was sutured during laparotomy. Symptoms of acute abdomen returned after 10 days. Pus-faecalperitonitis, symptoms of necro-hemorrhagic colitis and multilocal perforation of the colon were found during relaparotomy. Pancolectomy with end ileostomy was performed. Few hours since relaparotomy pacient died due to multiple organ failure. The purpose of this case report is to draw attention to a risk of multilocal colon perforation in patient treated with ipilumumab.
EN
In Poland, morbidity and mortality rates for melanoma are constantly increasing. In the case of inoperable disease or distant metastases, prognosis remains poor. For many years, dacarbazine has been the gold standard in systemic treatment. Recently, a significant progress in melanoma therapy has been observed. Introducing targeted therapy or immunotherapy significantly improved treatment outcomes. This review paper presents current knowledge on systemic treatment of advanced melanoma, including treatment availability in Poland.
EN
We report the synthesis, photochemical and photophysical properties and preliminary studies on biological effect of a new tritolylporphyrin dimer (T-D). Absorption and emission properties of T-D suggest its possible use in photodynamic therapy. T-D is capable of singlet oxygen production with 0.8 quantum yield. It also has a high photostability. The photodynamic properties of the dimer were examined following the growth of SKMEL 188 (human melanoma) cells irradiated with red light (cut off <630 nm). The surviving fraction of the cells decreased about 3-fold (vs. non-irradiated cells) for an 81 J/cm2 dose. Our results suggest that tritolylporphyrine dimer T-D may be an interesting hydrophobic sensitizer for photodynamic therapy.
EN
We present a case of 58-year old female patient that underwent surgery at Department of General and Vascular Surgery, Voivodeship Hospital of Traumatic Surgery in Warsaw for abdominal pain and nausea and palpable mass located in the left mesogastric region. During the surgical procedure, numerous, large nodules of the small intestine mesentery and the greater omentum were found. Histopathological examination demonstrated that they were melanoma metastases. When we confronted the reported case with available literature, we found only few similar reports.
EN
Introduction: About 25% of melanomas are localized in head and neck skin, and this particular localization is most diffi cult to treat, and the prognosis is less favorable. The depth of melanoma infi ltration (Clark and Breslau grade) into the skin is the main factor of local advancement of the disease. Surgical treatment is an essential therapeutic modality in patients with melanoma. Aim: The aim of this study was to evaluate results of our surgical treatment of melanomas in head and neck localisation, treated from 1997 to 2007 in Department of Oncological and Reconstructive Surgery in Center of Oncology IMSC in Gliwice. Material: We analysed group of 47 patients (aged 26 to 75 years, mean 49), treated by surgical excision of malignant melanoma in the head and neck region. Most of the patiens required to use free fl aps or skin graft technique to close posexcisional defect, on basis of clinical considerations. Results: The 5-year total survival for all patients was 62% and were dependent on depht of melanoma infi ltration and regional lymph node metastasis. The signifi cant prognostic factors were: localization of primary focus, local progression of disease, free microscopical excision margins sex and age. Conclusions: Prognosis in the patients with melanoma of the head and neck is unreliable and dependent on local advancement of disease and localization of primary focus. Surgical treatment is an essential therapeutic modality in patients with melanoma. Adiuvant radiotherapy after surgical treatment of melanoma of the head and neck is intended for the patiens with high risk of local or regional recurence of disease.
EN
Expression of N-cadherin an adhesion molecule of the cadherin family, in tumor cells is associated with their increased invasive potential. Many studies suggested the role of N-linked oligosaccharides as important factors that contribute to metastasis by influencing tumor cell invasion and adhesion. N-cadherin is a heavily glycosylated protein. We have analysed the carbohydrate profile of this protein synthesized in human melanoma cell lines: WM35 from the primary tumor site and WM239, WM9, and A375 from different metastatic sites. N-cadherin was immunoprecipitated with anti-human N-cadherin polyclonal antibodies. Characterisation of its carbohydrate moieties was carried out by SDS/PAGE electrophoresis and blotting, followed by immunochemical identification of the N-cadherin polypeptides and analysis of their glycans using highly specific digoxigenin or biotin labelled lectins. The positive reaction of N-cadherin from the WM35 cell line with Galanthus nivalis agglutinin (GNA), Datura stramonium agglutinin (DSA) and Sambucus nigra agglutinin (SNA) indicated the presence of high-mannose type glycans and biantennary complex type oligosaccharides with α2-6 linked sialic acid. N-cadherin from WM239, WM9, and A375 cell lines gave a positive reaction with Phaseolus vulgaris leukoagglutinin (L-PHA) and lotus Tetragonolobus purpureas agglutinin (LTA). This indicated the presence of tri- or tetra-antennary complex type glycans with α-fucose. In addition, N-cadherin from WM9 (lymphomodus metastatic site) and A375 (solid tumor metastatic site) contained complex type chains with α2-3 sialic acid (positive reaction with Maackia amurensis agglutinin - MAA). The results demonstrated that N-glycans of N-cadherin are altered in metastatic melanomas in a way characteristic for invasive tumor cells.
EN
Changes in CDKN2a gene are known to be linked with sporadic melanoma and hereditary predisposition to this cancer. In the Polish population mutations in the coding region of the CDKN2a gene are rather rare, therefore the attention has been focused on polymorphisms and alterations in uncoding regions such as 3' UTR. The aim of this study was to analyze two common polymorphisms, Ala148Thr and 500 C/G, and correlate them with the clinical course of melanoma. DNA from 285 patients was analyzed and found polymorphisms were correlated with the clinical parameters employing statistical methods. The obtained results allow us to conclude: (i) survival times of 500 C/G carriers vs. cumulating proportion surviving was not statistically significant; (ii) CDKN2a polymorphism 500 C/G correlated with Ala148Thr; (iii) no correlation was observed between the 500 C/G polymorphism and age of diagnosis, localization of primary melanoma and survival time; (iv) we did not find correlation between 500 C/G and type of cancer in the family; (v) changes in the CDKN2a gene were not found in patients with second cancer.
EN
Mutations in CDKN2A have been found in sporadic cutaneous malignant (CMM), in familial CMM and in other syndromes associated with melanoma. In this study DNA was obtained from 207 individuals and five cell lines. There were 157 CMM patients and 50 healthy members of melanoma patients families. The CMM group included patients with one or two melanoma cases in the family, families with dysplastic nevus syndrom (DNS) and patients with a spectrum of other types of cancers in the family. PCR-SSCP analysis and sequencing identified: six substitutions in codon 58 CGA/TGA (Arg/Stop), 16 substitutions GAC/GAT in codon 84 (Asp/Asp), six substitutions CGA /TGA in codon 148 (Arg/Thr), 14 substitutions G/C in 3'UTR and 4 double changes (two in codon 84 and 3'UTR; two in codon 148 and 3'UTR). The mutation identified in codon 58 was found in tissue only. Other substitutions were polymorphisms found in DNA from tissue and blood samples. Most of them were identified in sporadic CMM (six in codon 148 Ala /Thr, 12 in codon 84 Asp/Asp and six in 3'UTR). The frequency of the polymorphisms was also high in DNS and CMM/DNS families (four in codon 84 Asp/Asp and six in 3'UTR). No mutations or polymorphisms were found in CMM patients with one or two melanoma cases and CMM patients, with other cancers in family history. The analysis of the CDKN2A gene mutations in the Polish population demonstrated: (i) no germline mutations; (ii) a relatively high number of genetic changes in sporadic melanoma; (iii) a high number of polymorphisms in DNS and CMM/DNS families.
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2012
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vol. 59
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issue 4
647-652
EN
Ecto-5'-nucleotidase (eN, CD73) mediates extracellular adenosine production from 5'-AMP. Non-enzymatic functions of eN have also been reported. The aim of the study was to investigate the role of ecto-5'-nucleotidase in aggressive melanoma behaviour. Analysis of the involvement of eN in adhesion, migration and invasion revealed eN functions unknown to date. We found that following eN blockade by concanavalin A, the strength of adhesion to different ECM proteins was not altered, but at the same time the invasion ability of the cells was decreased. On the other hand, knocking down eN in melanoma cells did not influence cell invasion but abolished their migration on tenascin C (TnC). Ecto-5'-nucleotidase seems to fulfil a more distinct role as a receptor than as an enzyme in the cell interaction and mobility on TnC. Ecto-5'-nucleotidase activates also focal adhesion kinase and enhances the formation of complexes upon cell adhesion to TnC. All these observations prove that an eN-TnC complex is involved in cell migration and invasion and thus in the regulation of melanoma progression.
EN
INTRODUCTION In the early stages of cancerogenesis, TGF-β strongly inhibits the proliferation of epithelial cells and is described as a tumor suppressor. However, in further stages of this process, TGF-β can even promote the formation of a neoplasm. It can influence the tumor invasiveness and the ability of cancer to infiltrate the area of surrounding normal tissue. Stimulating proangiogenic factors such as IL-8 and VEGF can also contribute to angiogenesis in the tumor periphery. An elevated level of TGF-β strongly modifies the immune response of the organism through inhibiting the proliferation of T-cells and limiting the possibility of antigen presentation by specialized cells. Aim of the study. The aim of the study was to evaluate the expression of genes encoding TGF-β1 and its receptors: type I, II and III in melanoma cell culture after photodynamic therapy with Photolon in vitro. MATERIAL AND METHODS The study was conducted in three melanoma cell lines: C-32, Colo-892 and SH-4 (ATCC). The expression of genes encoding TGF-β1 and its receptors was estimated at the transcript stage (mRNA). RESULTS All of the photodynamic therapy parameters applied in the study resulted in a significant reduction of TGF-β1 and its receptors mRNA copy numbers per μg of the total RNA. CONCLUSIONS According to the data connected with the role of TGF-β in expressing a more malignant character in cancer cells, decreasing the TGF-β1 mRNA copy numbers after photodynamic therapy may be advantageous for the therapeutic process.
PL
WSTĘP W początkowym stadium kancerogenezy transformujący czynnik wzrostu β (transforming growth factor β – TGF-β) silnie hamuje proliferację komórek nabłonkowych i określany jest mianem supresora nowotworów. Jednak w późniejszych etapach tego procesu, czynnik ten może promować rozwój nowotworu: wpływać na jego inwazyjność oraz zdolność do naciekania prawidłowych tkanek. Przez stymulację czynników proangiogennych, takich jak IL-8 i VEGF, może także przyczyniać się do angiogenezy na obwodzie guza. Podwyższony poziom TGF-β silnie modyfikuje odpowiedź immunologiczną organizmu – hamuje proliferację limfocytów T oraz ogranicza możliwości prezentacji antygenów przez wyspecjalizowane komórki. Celem pracy była ocena ekspresji genów kodujących: TGF-β1 oraz jego receptory I, II i III w hodowlach komórek czerniaka, które poddano, w warunkach in vitro, terapii fotodynamicznej z Fotolonem. MATERIAŁ I METODY W badaniach wykorzystano trzy linie czerniaka: C-32, Colo-892 i SH-4 (ATCC). Ekspresję genów kodujących TGF-β1 i jego receptory oceniano na etapie transkryptów (mRNA). WYNIKI Zastosowanie przyjętych w pracy warunków terapii fotodynamicznej w przypadku wszystkich badanych linii czerniaka skutkuje znaczącą redukcją liczby kopii mRNA TGF-β1 i jego receptorów w przeliczeniu na μg RNA całkowitego. WNIOSKI W świetle informacji dotyczącej roli TGF-β w nabywaniu złośliwego charakteru komórek nowotworowych zmniejszenie liczby kopii mRNA TGF-β1 po przeprowadzeniu terapii fotodynamicznej może być korzystne dla przebiegu procesu terapeutycznego.
EN
Standard ocular tumor treatment includes brachytherapy, as well as proton therapy, particularly for large melanoma tumors. However, the effects of different radiation types on the metastatic spread is not clear. We aimed at comparing ruthenium (106Ru, emitting β electrons) and iodine (125I, γ-radiation) brachytherapy and proton beam therapy of melanoma implanted into the hamster eye on development of spontaneous lung metastases. Tumors of Bomirski Hamster Melanoma (BHM) implanted into the anterior chamber of the hamster eye grew aggressively and completely filled the anterior chamber within 8-10 days. Metastases, mainly in the lung, were found in 100% of untreated animals 30 days after enucleation. Tumors were irradiated at a dose of 3-10 Gy with a 106Ru plaque and at a dose of 6-14 Gy using a 125I plaque. The protons were accelerated using the AIC-144 isochronous cyclotron operating at 60 MeV. BHM tumors located in the anterior chamber of the eye were irradiated with 10 Gy, for the depth of 3.88 mm. All radiation types caused inhibition of tumor growth by about 10 days. An increase in the number of metastases was observed for 3 Gy of β-irradiation, whereas at 10 Gy an inhibition of metastasis was found. γ-radiation reduced the metastatic mass at all applied doses, and proton beam therapy at 10 Gy also inhibited the metastastic spread. These results are discussed in the context of recent clinical and molecular data on radiation effects on metastasis.
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2016
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vol. 63
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issue 3
533-541
EN
Aberrant expression of sialic acids or altered linkage types is closely associated with malignant phenotype and metastatic potential, and can have prognostic significance in human cancer. The present study was undertaken to evaluate whether expression of sialylated derivatives on melanoma cell surface is associated with tumour progression. Four cell lines (WM1552C, WM115, IGR-39 and WM266-4) were used in the study. Cell surface expression of sialic acids was evaluated by flow cytometry with the use of Maackia amurensis and Sambucus nigra lectins. Moreover, adhesion and migration potential of melanoma cells and involvement of sialic acids in these processes were analysed. We have demonstrated that WM266-4 cells have a significantly higher level of α2,3-linked sialic acid residues than other cells, whereas IGR-39 cells had lower expression of α2,6-linked sialic acids. The adhesion efficiencies of WM1552C and WM115 cells were significantly lower than that of IGR-39 and WM266-4 cells. In contrast, WM266-4 cells repaired scratch wounds at least twice as fast as other cells. Melanoma cell adhesion to fibronectin in the presence of Sambucus nigra agglutinin (SNA) was reduced only in IGR-39 and WM266-4 cells, whereas the impact of Maackia amurensis agglutinin (MAA) on this process was much more important. Migration efficiency of melanoma cells was reduced more strongly in the presence of MAA than SNA. In conclusion, our results show that melanoma progression is associated with the increased expression of α2,3-linked sialic acids on the cell surface and these residues could promote melanoma cell interaction with fibronectin.
EN
Human mitochondrial polynucleotide phosphorylase (hPNPase) is an exoribonuclease localized in mitochondria. The exact physiological function of this enzyme is unknown. Recent studies have revealed the existence of a relationship between induction of hPNPase mRNA and both cellular senescence and growth arrest of melanoma cells following β-interferon treatment. The aim of this study was to verify whether the augmented hPNPase mRNA level results in increase of the protein level. In several cell lines established from five metastatic melanoma patients we did not find any such correlation. However, an elevated level of hPNPase protein was observed in interferon-induced HeLa and Jurkat cells. This increase was correlated with a slight shortening of poly(A) tails of mitochondrial ND3 transcript.
EN
Epigenetics represents the mechanisms that infl uence the regulation and modifi cation of the expression of genetic material not related to the alterations in DNA sequences. These mechanisms include both DNA methylation and histone modifi cations. In the present article, we review current views on the role of aberrations of DNA hyper- and hypomethylation processes and the acetylation of histones, associated with genes that control the cell cycle, cell diff erentiation, DNA repair, apoptosis, cell signaling, angiogenesis, metabolism of xenobiotics and invasion, in the pathogenesis of melanoma. In addition, new strategies for treatment of melanoma associated with epigenetics are presented.
PL
Przez pojęcie epigenetyka należy rozumieć mechanizmy wpływające na regulację i modyfi kację ekspresji materiału genetycznego, jednocześnie niezmieniające sekwencji nukleotydów. Mechanizmy te obejmują zarówno metylację DNA, jak i modyfi kacje histonów. W artykule dokonano przeglądu aktualnych poglądów dotyczących zaburzeń procesów hiperi hipometylacji DNA oraz acetylacji histonów w patogenezie czerniaka, związanych z genami kontrolującymi cykl komórkowy, różnicowanie, naprawę DNA, apoptozę, sygnalizację komórkową, angiogenezę, metabolizm ksenobiotyków i powstawanie przerzutów. Ponadto przedstawiono nowe strategie leczenia czerniaka związane z epigenetyką.
EN
Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient’s prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal “avascular” areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue®, Sonazoid® and Definity®. This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node.
PL
Węzły wartownicze są pierwszymi węzłami chłonnymi na drodze spływu chłonki z okolicy guza pierwotnego. Wykluczenie lub potwierdzenie mikroprzerzutów w węźle wartowniczym odgrywa istotną rolę w ustalaniu stanu zaawansowania nowotworu, szczególnie nowotworu piersi i czerniaka, ponieważ bezpośrednio wpływa na rokowanie i wybór metody chirurgicznego leczenia. Obecnie śródoperacyjna biopsja węzłów wartowniczych z użyciem niebieskiego barwnika oraz radioizotopów są metodami z wyboru umożliwiającymi zidentyfikowanie węzłów wartowniczych. W przeciwieństwie do biopsji standardowe badanie ultrasonograficzne z reguły nie pozwala na ich uwidocznienie. Dzięki badaniu ultrasonograficznemu z użyciem środka kontrastującego oraz opcji obrazowania właściwych dla ultrasonografii ze środkami kontrastującymi można zdiagnozować położone obwodowo nieprawidłowe węzły chłonne. Metoda ta umożliwia ocenę węzłów w czasie rzeczywistym w każdej fazie naczyniowej, a także na uwidocznienie wewnątrzwęzłowych ogniskowych obszarów „nieunaczynionych”, które reprezentują obszary martwicy lub skupiska komórek nowotworowych. W ostatnich latach w wielu badaniach przeprowadzanych na zwierzętach i u ludzi wykazano, że badanie ultrasonograficzne z użyciem środka kontrastującego może uwidocznić węzeł wartowniczy i stać się rutynowym badaniem diagnostycznym. W badaniach tych zastosowano kilka środków kontrastujących, takich jak roztwór albuminy, skrobia hydroksyetylowana oraz SonoVue®, Sonazoid® i Definity®. Niniejsza praca stanowi podsumowanie obecnej wiedzy dotyczącej zastosowania ultrasonografii w diagnostyce węzłów chłonnych wartowniczych.
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