MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation

Hypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma (AII) to anaplastic astrocytoma (AIII) and secondary glioblastoma (sGB). In this study biopsy specimens from 51 patients with astrocytic tumors with radiologically proved progression from low to high-grade malignancy were investigated for the presence and consistency of MGMT promoter hypermethylation and TP53 mutations. For 27 patients biopsy samples both of primary tumors and their recurrences were available. For the other 24 patients histology of either the low-grade lesion or the high-grade recurrence was available. It was found that MGMT promoter hypermethylation and TP53 mutations are both frequent and early events in the progression of astrocytomas and that their status is consistent over time. No correlation was found between MGMT methylation status and the presence of TP53 mutations. In addition, no correlation was found between MGMT promoter hypermethylation and the type of TP53 mutations. These results argue against the putative TP53 G:C>A:T transition mutations suggested to occur preferentially in MGMT hypermethylated tumors

Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein

The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy

Bioactive components from potato juice as pâté additive and effect of its form on pâté quality

Celem niniejszej pracy była ocena wpływu dodatku soku z ziemniaka, będącego źródłem związków bioaktywnych o udokumentowanych właściwościach prozdrowotnych, zastosowanego w recepturze pasztetów na teksturę, mikrostrukturę i właściwości sensoryczne otrzymanych produktów. Sok z ziemniaka był dodawany w dwóch postaciach: świeżej lub utrwalonej metodą suszenia rozpyłowego. Przeprowadzone badania w skali półtechnicznej dowiodły, że zastosowanie odpowiedniej technologii wytwarzania pasztetu zawierającego dodatek bioaktywnych składników soku z ziemniaka pozwala uzyskać atrakcyjny sensorycznie, wysoko oceniany przez konsumentów produkt prozdrowotny. Wykazano również, że dodatek soku z ziemniaka, bez względu na zastosowaną formę, wywierał istotny wpływ na zmianę tekstury pasztetów i powodował wzrost: twardości, smarowności i lepkości oraz zmniejszenie adhezji. Od postaci w jakiej dodawany był sok z ziemniaka zależały natomiast stopień zdyspergowania tłuszczu w pasztetach i akceptacja konsumencka produktów. Dodatek suszonego soku z ziemniaka powodował wzrost rozdrobnienia kuleczek tłuszczowych i bardziej równomierne rozmieszczenie ich w strukturze wzbogaconego pasztetu. W przypadku zastosowania dodatku w formie świeżego soku z ziemniaka nie zaobserwowano statystycznie istotnych zmian analizowanych parametrów dyspersji tłuszczu w odniesieniu do pasztetu bez dodatku. Ocena atrakcyjności sensorycznej wykazała, że pasztet wzbogacony świeżym sokiem z ziemniaka uzyskał równie wysokie noty (zarówno ze względu na barwę, konsystencję, jak i smakowitość) jak pasztet bez dodatków wzbogacających. Natomiast pasztet wzbogacony suszonym sokiem z ziemniaka był w nieznacznie mniejszym stopniu akceptowany przez konsumentów.The objective of the research study was to assess the effect of potato juice, a source of bioactive compounds with evidenced health promoting properties, and used in the pâté recipe, on the texture, microstructure and sensory properties of the products obtained. The potato juice added had two forms: a fresh form and a spray-dried form. The analyses performed on a semi-industrial scale confirmed that the use of appropriate technology to manufacture pâté with bioactive components added to it made it possible to produce a sensory attractive, health promoting product that was highly appreciated by consumers. It was also shown that, regardless of its form, the potato juice additive significantly affected the change in the texture of pâtés and caused their hardness, spreadability, and viscosity to increase and their adhesion to decrease. However, the form in which potato juice was added to pâtés affected the degree of dispersion of fat in pâtés and the consumer acceptance of the products. Pâté enriched with pray-dried potato juice caused the dispersion of fat droplets to increase and those fat droplets also became more equally distributed in the enriched pâté structure. In the case the potato juice was added in the form of fresh juice, no statistically significant changes in the fat dispersion parameters analysed were found compared to pâté with no additive. The evaluation of the sensory attractiveness of pâté proved that pâté enriched with the fresh potato juice was rated very highly (in terms of colour, consistency, and tastiness) similar to the pâté without enriching additives. On the other hand, in the case of pâté enriched with the spray-dried potato juice, its acceptance by consumers was slightly lower