Elevated Pre-Treatment Serum MMP-7 Levels Are Associated with the Presence of Metastasis and Poor Survival in Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) is a rare cancer with a barely predictable clinical behaviour. Serum MMP-7 is a validated prognostic marker in urothelial bladder cancer, a tumour entity with large clinical, histological, and molecular similarity to UTUC. The serum MMP-7 levels have not yet been investigated in UTUC. In the present study, we determined MMP-7 concentrations in an overall number of 103 serum samples from 57 UTUC patients who underwent surgical or systemic (platinum or immune checkpoint inhibitor) therapy by using the ELISA method. In addition to pre-treatment samples, the serum samples collected at predefined time points after or during therapy were also investigated. Serum MMP-7 concentrations were correlated with clinicopathological and follow-up data. Our results revealed significantly, two-fold elevated pre-treatment serum MMP-7 levels in metastatic cases of UTUC in both the radical surgery- and the chemotherapy-treated cohorts (p = 0.045 and p = 0.040, respectively). In addition, high serum MMP-7 levels significantly decreased after radical surgery, and high pre-treatment MMP-7 concentrations were associated with shorter survival both in the surgery- and chemotherapy-treated cohorts (p = 0.029 and p = 0.001, respectively). Our results revealed pre-treatment serum MMP-7 as a prognostic marker for UTUC, which may help to improve preoperative risk-stratification and thereby improve therapeutic decision-making

Assessment of the usefulness of libs and ICP-MS for the characterization of nanoparticles in industrial and environmental samples

The need for analytical techniques capable for the detection and characterization of nanoparticles (NPs) in industrial and environmental matrices also grows along with the quickly expanding use of NPs in various products. Two candidate analytical techniques are laser induced breakdown spectroscopy (LIBS) and inductively coupled plasma mass spectrometry (ICP-MS). Both of these sensitive and versatile techniques provide elemental compositional information. Based on the success of the application of LIBS in aerosol analysis this technique can be expected to be similarly useful in NP monitoring applications, such as the detection of NPs in liquid or gaseous matrices, or for the monitoring of the properties of NPs produced by physical generation methods (e.g. electrical discharges or laser ablation). ICP-MS on the other hand has already proven itself useful in the literature, both in the solution or single particle analysis (spICP-MS) modes, for the characterization of nanoparticles. In recent years we also reported about the successful development of several ICP-MS based analytical methods for the compositional and dimensional analysis of NPs (e.g. [1, 2]). In our study we assessed the potential of LIBS and ICP-MS for nanoparticle detection and characterization both in on-line (only for LIBS) or off-line (following collection on a filter) mode. Dispersions of various types of nanoparticles (e.g. monometallic, bimetallic, oxide) in simulated or real liquid and gaseous industrial and environmental matrices were measured. Some NPs were obtained commercially, while others were generated by inlaboratory developed electrical (spark or arc) discharge generators. Additional and reference characterization of the nanoparticles were performed by electron microscopy (SEM, TEM) and scanning mobility particle sizer (SMPS). Size and mass detection limits were also calculated for on-line LIBS detection of nanoaerosols and for spICP-MS detection of NPs in aqueous nanodispersions

A kis sugárdózisú komputertomográfia szerepe a tüdőrákszűrésben

Bevezetés: A tüdőrák súlyos népegészségügyi probléma Magyarországon, ennek ellenére jelenleg nem működik orszá- gos szűrőprogram a betegség korai felismerésére. Az elmúlt évtizedek technikai fejlesztéseinek köszönhetően a tüdőrák diagnosztizálására alkalmas képalkotó vizsgálati módszerek érzékenysége sokat javult. Az egyik ilyen, széles körben ismertté vált új technológia a kis sugárdózisú komputertomográfia (LDCT). Célkitűzés: A jelen kutatás célja, hogy bemutassa az LDCT-nek mint a tüdőrák új szűrési technológiájának alkalma- zásával kapcsolatos szakmai álláspontokat és iránymutatásokat, valamint összegezze a technológiával kapcsolatos vizsgálatokat leíró tudományos szakirodalmat és más országok tüdőrákszűrési gyakorlatát. Módszer: Célzott irodalomkutatást végeztünk az LDCT-nek a tüdőrákszűrésben való alkalmazhatóságával kapcsolatban. Publikusan elérhető online adatbázisokban kerestünk szakmai irányelveket és ajánlásokat, valamint tudományos közleményeket, amelyek a tüdőrák szűrésével és a betegség korai felismerésével foglalkoznak. Eredmények: Irodalomkeresésünk során tüdőrákszűréssel, LDCT-vizsgálattal kapcsolatban 16 szakmai irányelvet és ajánlást azonosítottunk. Az LDCT-tüdőrákszűrés hatásosságára vonatkozóan végzett vizsgálatok közül 10 külföldi randomizált kontrollált vizsgálatot és 2 hazai vizsgálatot elemeztünk. 10 európai ország tüdőrákszűrési gyakorlatára vonatkozóan találtunk publikusan elérhető információt. Megbeszélés: A jelenleg elérhető evidenciák alapján az LDCT-szűrés javítja a tüdőrák, különösen a korai stádiumú tüdőrák diagnosztizálását, és csökkenti a tüdőrák-specifikus halálozás mértékét. Következtetés: Összességében megállapítható, hogy a magas rizikójú lakosság körében az LDCT bizonyítottan haté- kony szűrővizsgálat a tüdőrák korai felismerésére és a tüdőrák-specifikus halálozás csökkentésére. A jelenleg futó hazai és külföldi pilotprogramok eredményei várhatóan további evidenciával szolgálnak majd egy országos szintű LDCT-tüdőrákszűrési program bevezetéséhez

High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated in upper tract urothelial carcinoma (UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy (CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined in some patients by using ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002). High sPD-L1 levels were significantly associated with worse survival in both the RNU and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples (p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance