Syövän perinnöllisyys

Perinnöllinen syöpäalttius on tärkeää tunnistaa, koska geenivirheen kantajien syöpäriskiä voidaan pienentää.Suuren riskin geenivirheet tunnetaan varsin hyvin.Geenitietämys lisääntyy vauhdilla.Geenien läpiluenta uuden sukupolven massiivisella rinnakkaissekvensointitekniikalla mahdollistaa geenien tutkimisen nopeasti ja kustannustehokkaasti.Kasvaimesta saatavaa geenitietoa voidaan joskus hyödyntää potilaan hoidossa

Immuuniaktivaation vapauttajien haittavaikutukset : Miten tunnistan ja hoidan?

Immuuniaktivaation vapauttajat ovat uusia syöpälääkkeitä, joiden haittavaikutuksena voi ilmaantua tulehduksia. Jos päivystyspotilasta on hoidettu näillä lääkkeillä, hänen oireitaan tulee epäillä lääkkeen haittavaikutuksiksi, kunnes toisin on osoitettu. Samanaikainen infektio on mahdollinen

Edenneen ihomelanooman kehittyvä lääkehoito

Teema: Ihomelanooma. English summaryPeer reviewe

Different expression of BRAFV600E, ALK and PD-L1 in melanoma in children and adolescents : a nationwide retrospective study in Finland in 1990-2014

Background Pediatric melanoma may have a different biological background and more favorable prognosis compared with melanoma in adults. The aim of this study was to investigate melanoma in children and adolescents in the Finnish population in terms of incidence, clinical course, treatment, prognosis and BRAFV600E-, ALK- and PD-L1-positivity of the primary tumors. Materials and Methods Primary tumor samples and clinical records of all patients aged 0-19 years diagnosed with cutaneous melanoma in Finland in 1990-2014 were collected using the Finnish Cancer Registry database, Finnish hospitals and private pathology laboratories. BRAFV600E, ALK and PD-L1 were analyzed from 54 primary tumors and BRAFV600E from six metastasis samples. Results A total of 122 patients diagnosed with cutaneous melanoma were retrieved from the Cancer Registry database. The primary tumor samples of 73 patients were obtained for the review, and 56 cases were included in the study. The incidence of pediatric melanoma increased from 0.2 to 1.0/100 000 during the period 1990-2014. Spitzoid melanoma was the most common subtype (66%). The 10-year cancer-specific survival (CSS) was 88.7% in all patients. The 10-year-CSS did not differ in SLNB-positive or -negative groups. BRAFV600E was positive in 48%, ALK in 9% and PD-L1 in 2% of the tumors. BRAFV600E mutation was associated with 83% of melanoma deaths. Conclusions Young melanoma patients had more favorable prognosis and a different staining profile for BRAFV600E, ALK, and PD-L1 in primary tumor than reported in adults. SLNB status was not an indicator for survival. BRAFV600E-positive patients have worse prognosis and could benefit from surveillance and treatment similarly to adults.Peer reviewe

De novo assembly of genomes from long sequence reads reveals uncharted territories of Propionibacterium freudenreichii

Background: Propionibacterium freudenreichii is an industrially important bacterium granted the Generally Recognized as Safe (the GRAS) status, due to its long safe use in food bioprocesses. Despite the recognized role in the food industry and in the production of vitamin B12, as well as its documented health-promoting potential, P. freudenreichii remained poorly characterised at the genomic level. At present, only three complete genome sequences are available for the species. Results: We used the PacBio RS II sequencing platform to generate complete genomes of 20 P. freudenreichii strains and compared them in detail. Comparative analyses revealed both sequence conservation and genome organisational diversity among the strains. Assembly from long reads resulted in the discovery of additional circular elements: two putative conjugative plasmids and three active, lysogenic bacteriophages. It also permitted characterisation of the CRISPR-Cas systems. The use of the PacBio sequencing platform allowed identification of DNA modifications, which in turn allowed characterisation of the restriction-modification systems together with their recognition motifs. The observed genomic differences suggested strain variation in surface piliation and specific mucus binding, which were validated by experimental studies. The phenotypic characterisation displayed large diversity between the strains in ability to utilise a range of carbohydrates, to grow at unfavourable conditions and to form a biofilm. Conclusion: The complete genome sequencing allowed detailed characterisation of the industrially important species, P. freudenreichii by facilitating the discovery of previously unknown features. The results presented here lay a solid foundation for future genetic and functional genomic investigations of this actinobacterial species.Peer reviewe

Survival of women previously diagnosed of melanoma with subsequent pregnancy: a systematic review and meta-analysis and a single-center experience

Review[Abstract] Melanoma incidence has increased over the last few decades. How the prognosis of a previously diagnosed melanoma may be affected by a woman's subsequent pregnancy has been debated in the literature since the 1950s, and the outcomes are essential to women who are melanoma survivors in their childbearing years. The main objective of this systematic review is to improve the understanding of whether the course of melanoma in a woman may be altered by a subsequent pregnancy and to help clinicians' diagnosis. Eligible studies for the systematic review were clinical trials, observational cohort studies and case-control studies that compared prognosis outcomes for non-pregnant patients with melanoma, or pregnant before melanoma diagnosis, versus pregnant patients after a diagnosis of melanoma. The search strategy yielded 1101 articles, of which 4 met the inclusion criteria for the systematic review. All the studies were retrospective non-randomised cohorts with patients with melanomas diagnosed before pregnancy. According to our findings, a subsequent pregnancy was not a significant influence on the outcome of a previous melanoma. However, given the small number of identified studies and the heterogeneous data included, it is recommended to approach these patients with caution, and counselling should be given by known prognostic factors. We also reviewed the medical records of 84 patients of childbearing age (35.8 ± 6.3 years, range 21-45 years) who were diagnosed with cutaneous invasive melanoma in our hospital between 2008 and 2018 (N = 724). Of these, 11 (13.1%) had a pregnancy after melanoma diagnosis (age at pregnancy: 35.6 ± 6.3 years). No statistical differences in outcome were detected