Search results

1

THE ROLE OF OLIGOCHITOSANS IN AKT KINASE REGULATION

100%

Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Kucharska M.

Progress on Chemistry and Application of Chitin and its Derivatives

|

2015

|

vol. 20

73-81

EN

Among characteristic properties of cancers, there is their increased glycolytic activity.Contrary to normal cells, neoplastic cells use anaerobic glycolysis, even when a sufficient amount of oxygen is available. The intensity of the process is associated with a considerable demand for energy in the form of ATP. Akt, which - acting through the mTOR pathway - activates the HIF-1 factor, which in turn activates hexokinase that participates in glucose phosphorylation, stimulates the transport of glucose to cells via increasing glucose transporters (GLUT) and activates lactate dehydrogenase (which transforms pyruvate to lactate). Chitosan, as well as products of its degradation - oligochitosans - contribute to inhibiting the activity of the Akt kinase, and thus contribute to inhibiting excessive glycolytic activity of Ehrlich ascites tumor (EAT) cells and to decreasing proliferation of these cells.

2

INHIBITION OF EHRLICH ASCITES TUMOUR (EAT) CELLS PROLIFERATION THROUGH CHITOSAN-MEDIATED REGULATION OF ACTIVITY OF THE AKT PATHWAY

100%

Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Kucharska M.

|

EN

Isoenzyme M2 pyruvate kinase, which is a marker of cancer transformation, can take both tetramer (cytosol) and dimer (nucleus) forms. The former is responsible for ATP synthesis, and the latter demonstrates histone H1 kinase activity. Regulation of the expression of pyruvate kinase through which Akt controls the expression of genes involved in Ehrlich ascites tumour (EAT) cell proliferation, migration and death, also involves cross-talk with the other signalling pathways, transcription factors and co-regulatory proteins such as β-catenin and c-Myc. Treatment of EAT cells with chitosans significantly reduced their proliferation (by 45-60%), expression of nuclear β-catenin, c-Myc as well as cell migration. After 48–72 hours of treatment of the cell with oligochitosans, lower levels of p-Akt were detected. Simultaneously, decreased expression of isoenzyme M2 PK protein levels was observed. The dimeric form (nucleus) can participate in H1 histone phosphorylation, which contributes to increased EAT cell proliferation.

3

THE ROLE OF CHITOSAN IN AKT KINASE REGULATION ACTIVITY

86%

Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Kucharska M., Kazimierski J.

Progress on Chemistry and Application of Chitin and its Derivatives

|

2016

|

vol. 21

73-82

EN

A decrease in migration of tumor cells incubated with the investigated chitosan preparations was correlated with a decreased activity of MMP-2 and MMP-9 metalloproteinases, what significantly affected inhibition of tumor cell proliferation. In the investigations of the effects of various chitosan preparations on expression of PCNA, Akt and β-catenin in the normal human 184A1 cells and in breast carcinoma MCF7 cells evaluated at the protein level, significant differences in inhibition of expression of selected genes were noted in the tumor cells. Similarly as in the case of human cells, in mouse cells, the differences in expression of the investigated genes involved solely the Ehrlich carcinoma cells. In the presence of the investigated chitosan preparations, there was observed inhibition of expression of the N-cadherin, β-catenin, Akt and PCNA genes. In case of p21 protein, its level increased, similarly as in the human breast carcinoma cells, what may also be related to phosphorylation of the protein, its capture by the cytosol and prolonging its half-life as compared to the non-phosphorylated form. In case of the normal human 181A1 cells and mouse CRL 1636 cells, no significant alterations were noted in expression of the investigated genes in presence of the employed chitosan preparations.

4

EFFECT OF OLIGOCHITOSANS ON EXPRESSION OF INOS GENE IN EHRLICH ASCITES TUMOUR IN VITRO

86%

Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Zagajewski J., Niekraszewicz A.

Progress on Chemistry and Application of Chitin and its Derivatives

|

2012

|

vol. 17

141 - 148

EN

Oligochitosans obtained through degradation of macromolecules of chitosan with a high degree of deacetylation turned out to be biologically active, contributing to an increase of nitric oxide levels in Ehrlich ascites tumor (EAT) cells through inducing expression of the isoform of inducible nitric oxide synthase (iNOS) gene. An increase of NO levels in EAT cells in the presence of the investigated oligochitosans might contribute to nitrosylation of L-cysteine – an allosteric effector of the M2 isoenzyme of pyruvate kinase (PK), which switches the PK kinase activity, responsible for ATP synthesis, to the histone kinase activity that may participate in histone H1 phosphorylation. Lack of the histone activity of the PK M2 isoenzyme may contribute to decreased histone H1 phosphorylation and thus inhibit EAT cells proliferation.

5

Zakażenie HPV i jego związek z nowotworami złośliwymi

73%

Jach R., Dumin M., Radoń-Pokracka M., Basta A., Kojs Z., Karolewski K., Klimek M., Blacharz P., Ziętarski G., Dulińska-Litewka J.

Current Gynecologic Oncology

|

2010

|

vol. 8

|

issue 3

200-213

EN

Human papillomavirus (HPV) infection is the most frequent sexually transmitted disease. According to current estimates, there are about 5 500 000 new infections diagnosed annually. Among about 100 known types of HPV, 40 are designed as genital due to their preferential affinity to vulvar, vaginal, cervical, penile and anogenital epithelium. Chronic infection with types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 is associated with an elevated risk of malignant transformation, whereby the type 16 is detected in 50-55% of cases of invasive cervical cancer. Certain diagnosis of HPV infection at every stage of viral life cycle is provided by molecular virological techniques, while detection of viral DNA gains a novel significance as an adjunct to cytological study. Promising diagnostic potential in the setting of chronic HPV infections is associated with the test based on analysis of mRNA transcripts, enabling detection of active oncogenes E6 and E7 of the virus. This enables not only to confirm the presence of virus as such, but also to determine its activity gauged by initiation of transcription, i.e. the earliest phase of carcinogenesis. This is most useful the management of women infected by non-highly oncogenic HPV types. Most vulvar, vaginal and anal cancers are associated with HPV infection. Recently, the incidence of anogenital malignancies is increasing significantly. In view of continuously increasing number of HPV infections, it is reasonable to expect an increased number of anogenital malignancies and precursor lesions thereof, being diagnosed in the near future. Therefore, current epidemiological studied focus on inclusion of HPV testing (HPV DNA, HPV mRNA and early HPV genes) into large-scale screening programs for cervical cancer.

PL

Zakażenie HPV jest najczęstszą chorobą przenoszoną drogą płciową. Rocznie rozpoznaje się około 5 500 000 nowych zakażeń. Spośród 100 typów wirusów HPV 40 określa się mianem genitalnych z uwagi na ich preferencyjne występowanie w nabłonku okolic sromu, pochwy, szyjki macicy, penisa i okolicy anogenitalnej. Przetrwałe zakażenie wywołane przez typy 16., 18., 31., 33., 35., 39., 45., 51., 52., 56., 58., 59. wiąże się z wysokim ryzykiem rozwoju raka, przy czym typ 16. jest wykrywany w 50-55% przypadków inwazyjnego raka szyjki macicy. Pewne rozpoznanie zakażenia HPV w każdym stadium cyklu życiowego wirusa zapewniają molekularne metody wirusologiczne, a oznaczenie DNA HPV nabiera znaczenia jako procedura uzupełniająca badanie cytologiczne. Obiecujące możliwości diagnostyczne rozpoznania przetrwałego zakażenia HPV niesie ze sobą test oparty na wykrywaniu aktywnych onkogenów E6 i E7 wirusów HPV poprzez analizę transkryptów mRNA. Pozwala on określić nie tylko obecność, ale również aktywność wirusa, w tym rozpoczęcie transkrypcji, czyli najwcześniejszy etap karcinogenezy. Ma zastosowanie również wśród kobiet zakażonych typami wirusów HPV nienależącymi do grupy wysokoonkogennych. Przeważająca większość przypadków raka sromu, pochwy oraz odbytu związana jest z zakażeniem wirusem HPV. Częstość występowania nowotworów okolicy płciowo-odbytniczej znacząco zwiększyła się w ostatnich latach. Z uwagi na stały wzrost liczby zakażeń HPV należy w przyszłości spodziewać się diagnozowania większej liczby przypadków raków okolicy anogenitalnej i ich zmian prekursorowych. Dlatego też obecne badania epidemiologiczne koncentrują się na włączeniu testowania HPV (DNA HPV, mRNA HPV oraz genów wczesnych HPV) do programu masowych badań skryningowych raka szyjki macicy.

6

Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin

73%

Kocemba-Pilarczyk K., Ostrowska B., Trojan S., Aslan E., Kusior D., Lasota M., Lenouvel C., Dulińska-Litewka J.

|

2018

|

vol. 65

|

issue 1

101-109

EN

Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here.

Refine search results

THE ROLE OF OLIGOCHITOSANS IN AKT KINASE REGULATION

INHIBITION OF EHRLICH ASCITES TUMOUR (EAT) CELLS PROLIFERATION THROUGH CHITOSAN-MEDIATED REGULATION OF ACTIVITY OF THE AKT PATHWAY

THE ROLE OF CHITOSAN IN AKT KINASE REGULATION ACTIVITY

EFFECT OF OLIGOCHITOSANS ON EXPRESSION OF INOS GENE IN EHRLICH ASCITES TUMOUR IN VITRO

Zakażenie HPV i jego związek z nowotworami złośliwymi

Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin