Näkymätön Ninni : varhaislapsuuden vuorovaikutuskokemukset nuorisorikollisuuden selittäjänä

Tämä opinnäytetyö käsittelee varhaislapsuuden vuorovaikutuskokemusten merkitystä lapsen ja nuoren myöhempiin käytöshäiriöihin, sekä sitä kautta nuoren rikolliseen käyttäytymiseen. Tavoitteena on selvittää lasten ja nuorten kanssa työskentelevien sosiaalialan ammattilaisten näkemyksiä lapsen varhaisimpien vuorovaikutus- ja kiintymyssuhteiden vaikutuksista lapsen luomiin käytösmalleihin. Työssä selvitetään myös lapsen ja nuoren vuorovaikutus- tai kiintymyssuhteesta johtuvia mahdollisia oireita, sekä korjaavien kokemusten vaikutusta lapsen jo luomiin käytösmalleihin. Tutkimusmenetelmänä on käytetty laadullista, puolistrukturoitua teemahaastattelua. Tutkimusaineisto on kerätty haastattelemalla kahta Turun kaupungin perheoikeudellisen yksikön työntekijää. Haastattelu toteutettiin ryhmäkeskusteluna, jolloin tuloksista saatiin monipuolisempia sekä vuorovaikutteisempia. Haastattelurunkoa käytettiin suuntaa antavana apukeinona, ja haastateltavien itse esille tuomiin asioihin keskityttiin. Tietoperustana työssä käsitellään lapsen käytösmallien kehitystä ja siihen vaikuttavia tekijöitä, sekä kiintymyssuhdeteoriaa. Varhaislapsuus on herkkä vaihe käytösmallien ja aivojen kehityksessä, ja siellä saadut kokemukset vaikuttavat vielä aikuisiälläkin. Tukea kaipaaviin perheisiin kohdistetulla oikea-aikaisella sosiaalisilla toimilla moni lapsi saa tarvittavan määrän korjaavia kokemuksia, jotka voivat muuttaa oleellisesti hänen elämänsä suuntaa ja ennaltaehkäistä rikoksia. Toisaalta jos perhe tai lapsi ei saa oikeanlaista apua tarpeeksi varhaisessa vaiheessa, lapsuudessa muodostetut käytösmallit elävät vahvana läpi elämän

Mutational Signatures Associate With Survival in Gastrointestinal Carcinomas

Background/Aim: Mutational signatures reflect common patterns based on the counts of mutations and their sequence context. The prognostic value of these signatures, mirroring various carcinogenetic processes of cancers, are unexplored in gastrointestinal cancers. Our aim was to evaluate possible prognostic relevance of mutational signatures in gastrointestinal carcinomas after adjusting with the traditional prognostic factors. Materials and Methods: We used publicly available data from The Cancer Genome Atlas and Pan-Cancer Analysis of Whole Genomes to evaluate the associations between survival endpoints and activity of mutational signatures in seven types of gastrointestinal cancers. Results: Most strikingly, the high activity of age -related single-base substitution 5 (SBS5) and SBS40 signatures were in rectal adenocarcinomas associated with both improved overall survival (OS) [for SBS5 hazard ratio (HR) 0.130; 95% CI=0.03-0.56, for SBS40 HR=0.072; 95% CI=0.012-0.44, respectively] and similarly also to rectal cancer-specific survival. In patients with left-sided (but not right-sided) colon adenocarcinoma, the high activity of SBS2 signatures, formed due to APOBEC activity, predicted shortened OS. In pancreatic cancer, the high activity of SBS10b, caused by polymerase epsilon exonuclease proofreading defects, was associated both with longer OS (HR=0.44; 95% CI=0.205-0.96) and pancreatic cancer-specific survival (HR=0.32; 95% CI=0.112-0.91). Conclusion: Several mutational signatures seem to have clinically meaningful, cancer-specific associations with prognosis among gastrointestinal cancers.Peer reviewe

High Parity Predicts Poor Outcomes in Patients With Luminal B-Like (HER2 Negative) Early Breast Cancer : A Prospective Finnish Single-Center Study

While breast cancer prognoses are generally good, different molecular subtypes are known to have varying outcomes. Previous studies using breast cancer registries have suggested that high parity may be an adverse prognostic factor in luminal breast cancer, but breast cancer subtype definitions have varied and there have been few prospective studies. We therefore collected prospective data from patients diagnosed with early breast cancer at a single institution and followed them for a median of 8.5 years. All patients (N= 594) were treated according to Finnish national guidelines using modern treatment modalities in a Finnish university hospital. Clinicopathological surrogates of the intrinsic breast cancer subtypes were updated to match European Society for Medical Oncology 2015 Early Breast Cancer Clinical Practice Guidelines. The overall 10-year breast cancer-specific survival (BCSS) was 91.4%, with the longest 10-year BCSS observed in luminal A-like cancers (97.9%) and the worst in luminal B-like (HER2 positive) cancers (80.6%). Parity of >= 5 deliveries was also associated with poor BCSS (univariateP= 0.0020). However, when the subtypes were assessed separately in a multivariate analysis that included tumor size and nodal status, high parity remained significant only in luminal B-like (HER2 negative) cancers (HR = 2.63; 95% confidence interval = 1.04-6.62;P= 0.040). Our results suggest excellent overall 10-year BCSS but indicate that high parity is an adverse prognostic factor in luminal B-like (HER2 negative) breast cancers.Peer reviewe

Redox Regulating Enzymes and Connected MicroRNA Regulators Have Prognostic Value in Classical Hodgkin Lymphomas

There are no previous studies assessing the microRNAs that regulate antioxidant enzymes in Hodgkin lymphomas (HLs). We determined the mRNA levels of redox regulating enzymes peroxiredoxins (PRDXs) I–III, manganese superoxide dismutase (MnSOD), nuclear factor erythroid-derived 2-like 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) from a carefully collected set of 41 classical HL patients before receiving any treatments. The levels of redoxmiRs, miRNAs known to regulate the above-mentioned enzymes, were also assessed, along with CD3, CD20, and CD30 protein expression. RNAs were isolated from freshly frozen lymph node samples and the expression levels were analyzed by qPCR. mir23b correlated inversely with CD3 and CD20 expressions (p=0.00076; r=-0.523 and p=0.0012; r=-0.507) and miR144 with CD3, CD20, and CD30 (p=0.030; r=-0.352, p=0.041; r=-0.333 and p=0.0032; r=-0.47, resp.). High MnSOD mRNA levels associated with poor HL-specific outcome in the patients with advanced disease (p=0.045) and high miR-122 levels associated with worse HL-specific survival in the whole patient population (p=0.015). When standardized according to the CD30 expression, high miR212 and miR510 predicted worse relapse-free survival (p=0.049 and p=0.0058, resp.). In conclusion, several redoxmiRs and redox regulating enzyme mRNA levels associate with aggressive disease outcome and may also produce prognostic information in classical HL

Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas

<p>Abstract</p> <p>Background</p> <p>Triple-negative breast cancer (TNBC) and basal-like breast cancer (BLBC) are breast cancer subtypes with an especially poor prognosis. 8-Hydroxydeoxyguanosine (8-OHdG) is a widely used marker of oxidative stress and the redox-state-regulating enzymes peroxiredoxins (PRDXs) are efficient at depressing excessive reactive oxygen species. NF-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) are redox-sensitive transcription factors that regulate PRDX expression. This is the first study to assess oxidative stress and or cell redox state-regulating enzymes in TNBC and BLBC.</p> <p>Methods</p> <p>We assessed immunohistochemical expression of 8-OHdG, Nrf2, Keap1, PRDX III and PRDX IV in 79 women with invasive ductal breast carcinomas. Of these tumors, 37 represented TNBC (grade II-III tumors with total lack of ER, PR and human epidermal growth factor receptor 2 [HER2] expression). Control cases (n = 42) were ER-positive, PR-positive and HER2-negative. Of the 37 TNBCs, 31 had BLBC phenotype (TNBC with expression of cytokeratin 5/6 or epidermal growth factor receptor 1).</p> <p>Results</p> <p>Patients with TNBC had worse breast cancer-specific survival (BCSS) than the control group (p = 0.015). Expression of 8-OHdG was significantly lower in TNBC than in the non-TNBC group (p < 0.005). 8-OHdG immunostaining was associated with better BCSS (p = 0.01), small tumor size (p < 0.0001) and low grade (p < 0.0005). Keap1 overexpression was observed in the TNBC cohort (p = 0.001) and Keap1-positive patients had worse BCSS than Keap1-negative women (p = 0.014). PRDX IV was overexpressed in the TNBC <it>vs. </it>the non-TNBC group (p = 0.022).</p> <p>Conclusions</p> <p>Cellular redox state markers may be promising targets when elucidating the pathogenesis of TNBC.</p

Metformin Associates With Aggressive Features of Endometrial Cancer in Women With Type 2 Diabetes

Background/Aim: Preclinical studies on metformin use and endometrial cancer have been promising but epidemiological studies have reported variable results. This study aimed to assess if metformin use is associated with endometrial cancer aggressiveness and survival in women with type 2 diabetes (T2D). Patients and Methods: This retrospective hospital-based cohort consisted of women with T2D who were treated for endometrial cancer at the Oulu University Hospital, Finland, between 2007 and 2014. Results: The sample size was 121 patients: 58 metformin users and 63 metformin non-users. Intriguingly,type 2 histology, deep myometrial invasion and the presence of lymphovascular invasion were more common in the metformin user group. However, metformin use showed no association with overall survival and progression-free survival. Conclusion: Metformin use was associated with poorer prognostic factors in endometrial cancer patients with T2D.Peer reviewe

No Association Between Statin Use and the Prognosis of Endometrial Cancer in Women With Type 2 Diabetes

Preclinical studies have suggested statins have antiproliferative and anti-metastatic effects on endometrial cancer cells. Similarly, most previous epidemiological studies have reported a better prognosis of endometrial cancer in patients who used statins. In this study, we explored the role of statins in the prognosis of endometrial cancer in women with type 2 diabetes in a hospital-based cohort. This retrospective cohort consisted of 119 women with type 2 diabetes who were diagnosed and treated for endometrial cancer at Oulu University Hospital, Finland, between 2007 and 2014. The patients were classified as statin users (n = 58) and nonusers (n = 61) based on the type of medication they were using at the time of endometrial cancer diagnosis. Statin use showed no association with progression-free survival or overall survival in the whole cohort nor the subgroups with type I or type II histology, in lower or higher body mass index groups, or at an early or advanced stage. The results remained similar in the multivariate analysis after adjusting for the patient's age, cancer stage, and histology. Furthermore, statin use seemed not to have any association with most of the prognostic factors at the time of endometrial cancer diagnosis.Peer reviewe

Milloin rintasyövän immunologisesta hoidosta on hyötyä?

Vertaisarvioitu.• Immuunipuolustusta aktivoivat PD-1- ja PD-L1-vasta-aineet on otettu menestyksekkäästi käyttöön useiden levinneiden syöpien hoitomuotona. • Rintasyöpien hoitotulokset immunologisilla vasta-aineilla ovat olleet vaatimattomampia. • Kaksi immunologisen järjestelmän kiihdyttämiseen perustuvaa vasta-ainetta on saanut käyttöaiheen Suomessa immunogeenisyydeltään voimakkaimman levinneen rintasyövän alaryhmän hoidossa yhdessä solunsalpaajan kanssa. • Käyttöaiheen on saanut myös immunologinen hoito rintasyöpäkasvaimen pienentämiseen tarkoitetussa neoadjuvanttihoidossa. • Huomioiden immunologisen hoidon haitat ja kustannukset sekä kohtalaisen vaatimattomat hoitotulokset, parempia hoidon tehoa ennustavia tekijöitä kaivattaisiin.Peer reviewe