Sistemsko zdravljenje bolnikov s pljučnim rakom

Sistemsko zdravljenje nedrobnoceličnega raka pljuč (NDRP) je odvisno od različnih biooznačevalcev. Za izbiro sistemskega zdravljenja NDRP, ki nima ploščatocelične patohistologije danes potrebujemo molekularnogenetsko analizo. Le-ta nam poda informacijo ali ima NDRP morebitno genetsko alteracijo, za katero že imamo razvito tarčno obliko zdravljenja. Poznamo naslednje prediktivne molekularne alteracije: mutacije v genih EGFR, MET, BRAF, KRAS ter preureditve v genih ALK, ROS1, RET, NTRK in še druge. Skupna lastnost tarčnih zdravil pri NDRP je, da so visoko učinkovita, v peroralni obliki in da nudijo dobre možnosti dolgotrajnih zazdravljenj napredovale bolezni, ob tem pa je tveganje za hude neželene učinke nizko, kar celokupno vodi v dobro kvaliteto življenja

Treatment discontinuation and rechallenge of immune checkpoint inhibitors

Zaviralci imunskih kontrolnih točk (ZIKT) so novejša oblika sistemskega zdravljenja, ki so povezani s potencialni razvojem imunsko pogojenih neželenih dogodkov (irAE). Po razrešenem irAE obstaja možnost ponovne uvedbe ZIKT. Z naraščenjem števila bolnikov, ki so primerni za zdravljenje z ZIKT, se povečuje tudi število podatkov o varnosti in učinkovitosti ponovne uvedbe ZIKT po nastalem irAE. V prisevku sta povzeti dve nedavni študiji, ki analizirata podatke o ponovni uvedbi ZIKT po razrešenem irAE

Cumulative Delivery Rate after Providing Full Reimbursement In Vitro Fertilization Programme: A 6-Years Survey

Since 1983, Slovenia has been offering well-established, successful, and fully reimbursed IVF programme to infertile couples. On the grounds of data gathered at the Slovenian IVF units we aimed to determine whether the fully accessible IVF treatment system can provide notable success considering cumulative delivery rate (cDR). Longitudinal analysis of getting cDR was performed in 810 IVF cycles of 395 couples who for the first time attended the IVF programme in year 2006 and were followed until year 2012. We calculated the actual and the optimistic cDR. In women aged <38 years the actual cDR was 54% and optimistic DR was 83%, respectively. In women aged ≥38 years the actual cDR was 24 % and optimistic cDR was 27%. These results enable us to report that prospects of the treatment for the women aged <38 years, if they undergo all 6 available IVF cycles, are very positive and quite comparable to the chances of spontaneous conception. Even in older patients it is beneficial to repeat the IVF procedures. Therefore we consider the existing infertility treatment system in Slovenia as an example of good medical practice with high level of beneficence offered to the patients

Cumulus Cells Gene Expression Profiling in Terms of Oocyte Maturity in Controlled Ovarian Hyperstimulation Using GnRH Agonist or GnRH Antagonist

<div><p>In <em>in vitro</em> fertilization (IVF) cycles controlled ovarian hyperstimulation (COH) is established by gonadotropins in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists, to prevent premature luteinizing hormone (LH) surge. The aim of our study was to improve the understanding of gene expression profile of cumulus cells (CC) in terms of ovarian stimulation protocol and oocyte maturity. We applied Affymetrix gene expression profiling in CC of oocytes at different maturation stages using either GnRH agonists or GnRH antagonists. Two analyses were performed: the first involved CC of immature metaphase I (MI) and mature metaphase II (MII) oocytes where 359 genes were differentially expressed, and the second involved the two GnRH analogues where no differentially expressed genes were observed at the entire transcriptome level. A further analysis of 359 differentially genes was performed, focusing on anti-Müllerian hormone receptor 2 (<em>AMHR2</em>), follicle stimulating hormone receptor (<em>FSHR</em>), vascular endothelial growth factor C (<em>VEGFC</em>) and serine protease inhibitor E2 (<em>SERPINE2</em>). Among other differentially expressed genes we observed a marked number of new genes connected to cell adhesion and neurotransmitters such as dopamine, glycine and γ-Aminobutyric acid (GABA). No differential expression in CC between the two GnRH analogues supports the findings of clinical studies where no significant difference in live birth rates between both GnRH analogues has been proven.</p> </div

Patients baseline characteristics.

<p>age, body mass index (BMI), serum oestradiol level on day of hCG, number of retrieved oocytes; proportions of degenerated oocytes, metaphase I oocytes (MI), metaphase II oocytes (MII), fertilized oocytes, unfertilized metaphase II oocytes (MII-NF) and metaphase II oocytes developed to the blastocyst stage (MII-BL). Significance of differences between the two treatment groups was assessed using Student's t-test; two-tailed p-values are shown.</p

Subgroup of genes connected to follicle stimulating hormone (FSH) and luteinizing hormone (LH) from a top ranked gene network.

<p>It is associated with Post-Translational Modification, Cellular Development, Cellular Growth and Proliferation as identified by Ingenuity Pathways Analysis. Top ranked gene network was obtained from comparisons of differential expression between CC MII and CC MI. Genes are represented as nodes, and the biological relationship between two nodes is represented as edge (line): a plain line indicates direct interaction, a dashed line indicates indirect interaction; a line without arrowhead indicates binding only, a line finishing with a vertical line indicates inhibition; a line with an arrowhead indicates ‘acts on’. The green colour intensity of the nodes indicates the degree of down-regulation in the CC MII group. CC MI: cumulus cells of metaphase I oocytes. CC MII: cumulus cells of metaphase II oocytes.</p

A list of patients included in GnRH agonist and GnRH antagonist group with a number CC samples regarding to oocyte stage.

<p>CC MI: cumulus cells of metaphase I oocytes; CC MII-NF: cumulus cells of unfertilized metaphase II oocytes; CC MII-BL: cumulus cells of metaphase II oocytes developed to blastocyst stage embryo.</p

Experimental design.

<p>number of patients included in the study with respect to the two GnRH analogue treatments and the number of collected CC samples; CC MI: cumulus cells of metaphase I oocytes; CC MII-NF: cumulus cells of unfertilized metaphase II oocytes; CC MII-BL: cumulus cells of metaphase II oocytes developed to the blastocyst stage.</p

Expression (log2 fold change) of <i>VEGFC</i>, <i>SERPINE2</i>, <i>AMHR2</i> and <i>FSHR</i> from microarrays and qPCR showing contrast between CC MII and CC MI.

<p>Bars represent expression of CC MII vs. CC MI as log2 fold change with standard deviation. Blue represents microarray data and red qPCR data. Correlation coefficient (r = 0.98) and p value (p = 0.02) indicate strong and significant correlation between microarray and qPCR data. Corr r: Pearson correlation coefficient with p value between microarray and qPCR values. CC MI: cumulus cells of metaphase I oocytes. CC MII: cumulus cells of metaphase II oocytes.</p