Search results

1

The correlation analysis of WWOX expression and cancer related genes in neuroblastoma- a real time RT-PCR study

100%

Nowakowska M., Płuciennik E., Wujcicka W., Sitkiewicz A., Kazanowska B., Zielińska E., Bednarek A.

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2014

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vol. 61

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issue 1

91-97

EN

Neuroblastoma is one of the most common paediatric cancers, described as unpredictable due to diverse patterns of behaviour. WWOX is a tumour suppressor gene whose expression is reduced in many tumour types. Loss of its expression was shown to correlate with more aggressive disease stage and mortality rate. The aim of this study was to investigate the role of the WWOX tumour suppressor gene in neuroblastoma formation. We performed real-time RT-PCR to analyse levels of WWOX expression in 22 neuroblastic tumour samples in correlation with genes involved in cell cycle regulation (CCNE1, CCND1), proliferation (MKI67), apoptosis (BCL2, BIRC5, BAX) and signal transduction (EGFR, ERBB4). We also evaluated two potential mechanisms - promoter methylation (MethylScreen method) and loss of heterozygosity (LOH) status, which could be connected with regulation of WWOX gene expression. We found a positive correlation between WWOX gene and BCL2 and HER4 JM-a and negative with cyclin D1 and E1. Our observations are consistent with previous findings and emphasise the role of WWOX in cell cycle and apoptosis regulation. Moreover, strong positive association with HER4 JM-a in this tumour type may indicate a role for WWOX in neuroblastoma cell differentiation. The presented results indicate that LOH in locus D16S3096 (located in intron 8) may be involved in the regulation of WWOX mRNAexpression. However, no association between methylation status of WWOX promoter and its expression was observed.

2

Molecular biology of sporadic vestibular schwannomas including genetic and epigenetic alterations

88%

Makuszewska M., Litwiniuk-Kosmala M., Bartoszewicz R., Niemczyk K.

Polski Przegląd Otorynolaryngologiczny

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2020

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vol. 9(3)

23-29

EN

Introduction: Vestibular schwannomas (VS) are benign tumors developing from the myelin-producing Schwann cells, which surround the vestibular branches of the auditory nerve. The vast majority occur sporadically and a small proportion are associated with neurofibromatosis type 2 (NF2). Most sVS are slow-growing neoplasms; however some have a cystic structure, show more rapid growth, cause more frequently paralysis of the facial nerve, and brainstem compression. The molecular hallmark of both sporadic and NF-2 associated VS is the inactivation of the tumor-suppressor gene NF2, also called merlin gene. Purpose: The paper presents the current knowledge on the molecular biology of VS, including: information on genetic and epigenetic aberrations, changes in gene expression and specific microRNA expression profiles.

3

New method for quantitative analysis of GD2 ganglioside in plasma of neuroblastoma patients

88%

Czaplicki D., Horwacik I., Kowalczyk A., Wieczorek A., Bolek-Marzec K., Balwierz W., Kozik A., Rokita H.

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issue 3

423-431

EN

Neuroblastoma, the most common extracranial solid tumour of childhood, is a malignancy of unknown origin and non-specific symptoms. One of the markers of the disease is GD2 ganglioside (disialoganglioside), which is abundantly expressed on the surface of neuroblastoma cells. Gangliosides are known to be shed by tumour cells and this phenomenon can be significant in cancer progression as they inhibit a number of immune responses both in vitro and in vivo. In search for novel markers useful in monitoring and prognosis of neuroblastoma, we developed and validated a new quantitative method of GD2 ganglioside analysis in human blood plasma. We evaluated the level of gangliosides in blood serum of 34 neuroblastoma patients using high-performance liquid chromatography. The technique was used to detect fluorescently labelled oligosaccharides derived from serum glycosphingolipids by enzymatic digestion with ceramide glycanase. The developed method allowed determination of GD2 concentrations at the picomole level and required only 40 µl of plasma, which should be particularly useful when the quantity of clinical material is limiting. Moreover, this method can be applied to study concentration of other gangliosides, as shown for GD3 ganglioside. Analysis of plasma samples from the 34 neuroblastoma patients did not reveal any correlations between the concentration of GD2 ganglioside and clinical parameters, including the results of therapy; it showed, however, that the concentration of GD2 ganglioside in the plasma of neuroblastoma patients decreased substantially in the course of treatment.

4

THE EFFECTS OF CARVACROL ON OXIDATIVE STRESS PARAMETERS AND APOPTOSIS PROCESS VIA TRPA1 CHANNELS IN NEUROBLASTOMA CELLS

88%

Gunal M. Y., Ovey I. S.

Acta Poloniae Pharmaceutica - Drug Research

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2019

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vol. 76

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issue 3

535-542

EN

Objectives: This study is a preliminary study to investigate the effects of carvacrol (CRV) obtained from thyme on the apoptosis process in neuroblastoma cells. Methods: In this study, seven groups were designed as control, CRV, CRV + AP-18, CRV + melatonin, CRV + melatonin + AP-18, melatonin and melatonin + AP-18. All groups were stimulated using CNM (cinnamaldehyde) which is TRPA1 channel stimulator. Levels of Reactive oxygen species (ROS), caspase-3, caspase-9, mitochondrial depolarization, apoptosis, intracellular free calcium and 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) were measured. Data were evaluated using one way ANOVA analysis. Results: Levels of ROS, mitochondrial depolarisation, caspase-3 and -9 and apoptosis were significantly higher in all groups treated with CRV compared to control (P <0.05). On the other hand, in melatonin-treated group and melatonin + AP-18 treated group, ROS and caspase-3 were significantly lower than control (P <0,05). MTT levels were significantly decreased in all groups treated with CRV compared to control (P <0.05). On the other hand, in melatonin-treated group and melatonin + AP-18 treated group, MTT was higher than control(P <0,05). Conclusion: It has also been shown that CRV can also exert its effects through TRPA1 channels in neuroblastoma cells, which may accelerate the apoptosis process by acting on these channels, increasing ROS and caspase-3 levels. Changes in MTT levels support this result. However, in order to better evaluate the effects of CRV on the apoptosis process, it would be useful to investigate changes in caspase-9, mitochondrial depolarization, and calcium channels.

5

Effective treatment of severe hypertensive crisis in 2-year-old child with neuroblastoma

88%

Raciborska A., Bilska K., Antoniewicz J., Rychłowska-Pruszyńska M., Rodriguez-Galindo C., Fijałkowska A.

OncoReview

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2015

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vol. 5

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issue 2

A53-56

EN

We describe a case of a 2-year-old boy with neuroblastoma and high catecholamine levels which developed a severe hypertensive crisis. An oral propranolol and oral angiotensin-converting enzyme inhibitor were used with a mild short transient benefit. However, an intravenous labetalol and oral doxazosin used for over 3 weeks resulted in successful blood pressure control. This report highlights the prolonged use of α and β-adrenergic antagonist therapy in children with neuroblastoma with refractory catecholamine-induced hypertension.

6

Metody detekcji przerzutów komórek neuroblastoma do szpiku kostnego

75%

Szewczyk K., Balwierz W.

Zeszyty Naukowe Towarzystwa Doktorantów Uniwersytetu Jagiellońskiego. Nauki Ścisłe

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2012

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issue 5

77-85

EN

Neuroblastoma (NB), which is derived from the embryonic neural cells, is one of the most common childhood cancers (7–10%). Despite an increase in treatment intensity, the curability of patients, especially those in the high risk group, is still unsatisfactory. One of the causes of therapy failure may be the presence of cancer stem cells that survive chemotherapy and are capable of colonizing the bone marrow cavities. . A very important element in diagnosis of NB is the examination of bone marrow conducted either to confirm or exclude the presence of metastases. The currently used laboratory methods enable the detection of even a single NB cell and allow the monitoring of the minimal residual disease (MRD).

7

Analysis of genes involved in response to doxorubicin and a GD2 ganglioside-specific 14G2a monoclonal antibody in IMR-32 human neuroblastoma cells

75%

Horwacik I., Durbas M., Boratyn E., Sawicka A., Węgrzyn P., Krzanik S., Górka A., Drożniak J., Augustyniak E., Kowalczyk A., Rokita H.

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2015

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vol. 62

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issue 3

423-433

EN

Neuroblastoma is the most common extra-cranial solid tumor of childhood and it is characterized by the presence of a glycosphingolipid, GD2 ganglioside. Monoclonal antibodies targeting the antigen are currently tested in clinical trials. Additionally, several research groups reported results revealing that ganglioside-specific antibodies can affect cellular signaling and cause direct cytotoxicity against tumor cells. To shed more light on gene expression signatures of tumor cells, we used microarrays to analyze changes of transcriptome in IMR-32 human neuroblastoma cell cultures treated with doxorubicin (DOX) or a mouse monoclonal antibody binding to GD2 ganglioside 14G2a (mAb) for 24 h. The obtained results highlight that disparate cellular pathways are regulated by doxorubicin and 14G2a. Next, we used RT-PCR to verify mRNA levels of selected DOX-responsive genes such as RPS27L, PPM1D, SESN1, CDKN1A, TNFSF10B, and 14G2a-responsive genes such as SVIL, JUN, RASSF6, TLX2, ID1. Then, we applied western blot and analyzed levels of RPS27L, PPM1D, sestrin 1 proteins after DOX-treatment. Additionally, we aimed to measure effects of doxorubicin and topotecan (TPT) and 14G2a on expression of a novel human NDUFAF2 gene encoding for mimitin protein (MYC-induced mitochondrial protein) and correlate it with expression of the MYCN gene. We showed that expression of both genes was concomitantly decreased in the 14G2a-treated IMR-32 cells after 24 h and 48 h. Our results extend knowledge on gene expression profiles after application of DOX and 14G2a in our model and reveal promising candidates for further research aimed at finding novel anti-neuroblastoma targets.

8

Rola przeszczepiania autologicznych krwiotwórczych komórek macierzystych w leczeniu guzów litych

63%

Młot B., Gawroński K., Oborska S., Pielichowski W., Rzepecki P., Waśko-Grabowska A.

Current Gynecologic Oncology

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2011

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vol. 9

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issue 3

169-185

EN

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has been used in the treatment of solid tumors since the ‘80s. Standard indications include breast cancer, ovarian cancer and germ cell tumors. Results of several phase II trials confirmed a beneficial effect of this therapeutic strategy on recurrence-free survival and total survival compared with conventional chemotherapy. Unfortunately, in most types of solid tumors, this effect has not been confirmed by phase III trials. Subsequently, the number of autologous transplantations in breast cancer decreased considerably. There is no evidence for any favorable effect of HDC in brain tumors and small cell lung cancer. According to 2006 EBMT recommendations, HDC followed by administration of hematopoietic cells is a therapeutic option in cases of therapy-resistant or recurrent primarily extragonadal germ cell tumors. A matter of debate is the use of this technique with similar indications in patients with germ cell tumors originating in the gonads. The first report on the effectiveness of HDC as first-line treatment of non-epithelial soft tissue tumors was by Pritchard et al. (1998). They documented improved event-free survival and total survival after administration of high doses of melphalan in children with stage IV neuroblastoma, achieving complete or very favorable partial remission after completed induction chemotherapy and surgical treatment. To date, neuroblastoma remains the only neoplasm, where randomized trials in children confirmed a favorable effect of transplantation of autologous hematopoietic cells on final treatment outcome.

PL

Wysokodawkowa chemioterapia (HDC) z następowym przeszczepieniem autologicznych komórek krwiotwórczych (ASCT) jest stosowana w leczeniu guzów litych od lat 80. Najczęstszymi wskazaniami były: rak sutka, rak jajnika i guzy zarodkowe. Wyniki wielu badań drugiej fazy wskazywały na korzystny wpływ tej metody leczenia na przeżycie wolne od nawrotu i całkowite przeżycie w porównaniu z konwencjonalną chemioterapią. Niestety, dla większości typów guzów litych efekt ten nie został potwierdzony w badaniach trzeciej fazy. Znacząco spadła liczba autologicznych przeszczepień w raku sutka. Nie znaleziono dowodów o wyższości HDC w guzach mózgu i raku drobnokomórkowym płuca. Według stanowiska EBMT z 2006 roku wysokodawkowa chemioterapia z następową podażą komórek krwiotwórczych stanowi opcję terapeutyczną w przypadkach opornych bądź nawrotowych guzów zarodkowych o pierwotnym punkcie wyjścia pozagonadalnym. Dyskusyjna jest sprawa zastosowania tej metody w podobnych wskazaniach u chorych z guzem zarodkowym wywodzącym się z gonad. Pierwszym doniesieniem potwierdzającym skuteczność zastosowania wysokodawkowej chemioterapii w leczeniu pierwotnym nowotworów nienabłonkowych tkanek miękkich była praca Pritcharda i wsp. z 1998 roku. Autorzy udokumentowali w niej poprawę przeżycia wolnego od zdarzeń i całkowitego przeżycia (ES i OS) po zastosowaniu wysokich dawek melfalanu u dzieci w stadium IV neuroblastoma, które uzyskały całkowitą lub bardzo dobrą częściową remisję po zakończeniu chemioterapii indukcyjnej i leczeniu operacyjnym. Do chwili obecnej neuroblastoma pozostaje jedynym nowotworem, w przypadku którego w badaniu randomizowanym (u dzieci) wykazano korzystny wpływ przeszczepienia autologicznych komórek krwiotwórczych na ostateczne wyniki leczenia.

9

Skuteczność preparatu Trivagin w przywróceniu i utrzymaniu prawidłowego ekosystemu pochwy u kobiet leczonych z powodu nawracającej waginozy bakteryjnej

63%

Harasim-Dylak A., Roguska M., Maździarz A.

Current Gynecologic Oncology

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2011

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vol. 9

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issue 4

245-252

EN

Physiologic vaginal bacterial flora is a dynamic balanced ecosystem encompassing microbes populating vaginal mucosa, products of their metabolism and secretions of vaginal glands. Normal composition of vaginal flora may be altered by pathogenic bacteria, fungi and yeasts, chemical factors, disturbed natural immune processes and also due to iatrogenic intervention, e.g. antibiotic therapy and surgical procedure. The aim of the present paper is to assess the role of Trivagin in restoring and maintaining normal vaginal flora in women with recurrent bacterial vaginosis (BV). Study population consisted of 60 women. Thereof, 30 women were patients with recurrent genital infections. Control group included randomly selected asymptomatic women. All patients underwent a standard gynecologic examination with assessment of vaginal secretion. Next, Trivagin has been administered for 20 days. Upon completion of treatment, vaginal secretion was re-assessed as direct sample study. Results obtained in both groups were compared. In the study population, signs and symptoms of BV resolved in 65% and subjective improvement was seen in 91% of the patients, according to the Amsel criteria. Conclusions: Trivagin promotes restoration and maintenance of physiologic vaginal flora in women with recurrent BV. Unique composition of the preparation (Lactobacillus rhamnosus, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus plantarum) including species most frequently found in Polish females, enables an effective restoration of vaginal flora, while easy application by oral route significantly improves compliance and treatment outcomes.

PL

Fizjologiczna flora bakteryjna pochwy stanowi dynamiczną równowagę pomiędzy mikroorganizmami zasiedlającymi jej błonę śluzową a produktami ich metabolizmu i wydzieliną gruczołów. Prawidłowy skład flory może zostać naruszony przez chorobotwórcze bakterie, grzyby, czynniki chemiczne, zaburzenia naturalnych procesów immunologicznych, a także na skutek jatrogennej ingerencji, takiej jak stosowanie antybiotyków czy przebycie zabiegów chirurgicznych. Celem pracy była ocena wpływu stosowania preparatu Trivagin na przywrócenie prawidłowej flory bakteryjnej u kobiet z nawracającą waginozą pochwy (bacterial vaginosis, BV). Materiał stanowiło 60 kobiet. Grupa badana obejmowała 30 pacjentek z nawracającymi infekcjami w obrębie narządów płciowych. Grupa kontrolna składała się z 30 losowo wybranych bez-objawowych kobiet. U wszystkich pacjentek przeprowadzono badanie ginekologiczne z oceną wydzieliny pochwowej. Następnie przez 20 dni stosowano preparat Trivagin. Po ukończeniu leczenia ponownie przeprowadzono ocenę wydzieliny pochwowej w preparacie bezpośrednim. Porównano wyniki w obu grupach. U 65% kobiet w grupie badanej stwierdzono ustąpienie cech i objawów bakteryjnej waginozy oceniane według kryteriów Amsela oraz subiektywną poprawę w ocenie 91% pacjentek. Wnioski: Trivagin pomaga w przywróceniu i utrzymaniu fizjologicznej flory pochwy wśród kobiet z nawracającymi infekcjami bacterial vaginosis. Wyjątkowy skład preparatu (Lactobacillus rhamnosus, Lactobacillus gasseri, Lactobacillus fermentum, Lactobacillus plantarum) uwzględniający gatunki najczęściej występujące w Polsce pozwala na właściwe odbudowanie naturalnej flory bakteryjnej, a łatwość jego stosowania - podaż doustna - w znaczący sposób poprawia wyniki leczenia.

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The correlation analysis of WWOX expression and cancer related genes in neuroblastoma- a real time RT-PCR study

Molecular biology of sporadic vestibular schwannomas including genetic and epigenetic alterations

New method for quantitative analysis of GD2 ganglioside in plasma of neuroblastoma patients

THE EFFECTS OF CARVACROL ON OXIDATIVE STRESS PARAMETERS AND APOPTOSIS PROCESS VIA TRPA1 CHANNELS IN NEUROBLASTOMA CELLS

Effective treatment of severe hypertensive crisis in 2-year-old child with neuroblastoma

Metody detekcji przerzutów komórek neuroblastoma do szpiku kostnego

Analysis of genes involved in response to doxorubicin and a GD2 ganglioside-specific 14G2a monoclonal antibody in IMR-32 human neuroblastoma cells

Rola przeszczepiania autologicznych krwiotwórczych komórek macierzystych w leczeniu guzów litych

Skuteczność preparatu Trivagin w przywróceniu i utrzymaniu prawidłowego ekosystemu pochwy u kobiet leczonych z powodu nawracającej waginozy bakteryjnej