The Role of an Oncoprotein CIP2A in Breast Cancer

Cancerous inhibitor of PP2A (CIP2A) is an oncoprotein expressed in several human cancer types. Previously, CIP2A has been shown to promote proliferation of cancer cells. Mechanistically, CIP2A is known to inhibit activity of a tumor suppressor protein phosphatase 2A (PP2A) towards an oncoprotein MYC, further stabilizing MYC in human cancer. However, the molecular mechanisms how CIP2A expression is induced during cellular transformation are not well known. Also, expression, functional role and clinical relevance of CIP2A in breast cancer had not been studied before. The results of this PhD thesis work demonstrate that CIP2A is highly expressed in human breast cancer, and that high expression of CIP2A in tumors is a poor prognostic factor in a subset of breast cancer patients. CIP2A expression correlates with inactivating mutations of tumor suppressor p53 in human cancer. Notably, we demonstrate that p53 inactivation up-regulates CIP2A expression via increased expression of an oncogenic transcription factor E2F1. Moreover, CIP2A promotes expression of E2F1, and this novel positive feedback loop between E2F1 and CIP2A is demonstrated to regulate sensitivity to both p53-dependent and -independent senescence induction in breast cancer cells. Importantly, in a CIP2A deficient breast cancer mouse model, abrogation of CIP2A attenuates mammary tumor formation and progression with features of E2F1 inhibition and induction of senescence. Furthermore, we demonstrate that CIP2A expression defines the cellular response to a senescence-inducing chemotherapy in breast cancer. Taken together, these results demonstrate that CIP2A is an essential promoter of breast cancer tumor growth by inhibiting senescence. Finally, this study implicates inhibition of CIP2A as a promising therapy target for breast cancer.Siirretty Doriast

Men with Crohn's disease may have an increased risk for head and neck squamous cell carcinoma - a nationwide register study

Objective Our goal was to study inflammatory bowel disease (IBD) patients' risk of head and neck squamous cell carcinoma (HNSCC), compared to general population.Materials and methods We performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort's complementary age-year-sex-person-year incidence to that of the whole Finnish population.Results About 70,567 patients were diagnosed with IBD (Crohn's disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065-1.614, P = 0.062). When calculating Crohn's disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn's disease (SIR 1.951, 95% CI 1.216-2.935, P = 0.025).Conclusion An increased risk for HNSCC was found in men with Crohn's disease compared to the Finnish population expectations.Clinical relevance This study provides information that would improve follow-up protocols and treatment guidelines of IBD.Peer reviewe

LET’S MOVE IT -LIIKUNTAINTERVENTION VASTAANOTON LAADULLINEN ARVIOINTI VÄHÄN LIIKKUVIEN NUORTEN HAASTATTELUISTA

Nuorten vähäiseen liikkumiseen on pyritty tarttumaan monin keinoin. Monissa hyvinvoinnin edistämiseen pyrkivissä interventioissa pyritään muuttamaan kohderyhmän käsityksiä tai taitoja elintapamuutoksen aikaansaamiseksi. Usein oletetaan, että interventioiden kohteet ymmärtävät sanoman ja viestit samoin kuin suunnittelijat ovat ne tarkoittaneet. Olisi kuitenkin tärkeää myös empiirisesti tutkia, miten kohderyhmä havaitsee liikunnan edistämisen toimenpiteet ja viestit. Tässä tutkimuksessa arvioidaan Let’s Move It -liikuntaintervention vastaanottoa vähän liikkuvien datanomiopiskelijoiden joukossa. Ohjelman tavoitteena oli mm. tiedon, motivaation ja taitojen lisäämisen sekä ympäristömuutosten kautta lisätä liikuntaa erityisesti vähän liikkuvien nuorten osalta ja vähentää passiivista aikaa. Tämä ryvässatunnaistetun vaikuttavuustutkimuksen ensimmäisessä tutkimuskohortissa toteutettu osatutkimus pyrki selvittämään, miten ryhmätapaamisiin osallistuneet nuoret ovat ymmärtäneet intervention tavoitteet ja viestit. Puolistrukturoidut haastattelut (n=14, kaksi ryhmä- ja kahdeksan yksilöhaastattelua) analysoitiin kirjaimellisen ja tulkitsevan luennan kautta hyödyntäen laadullisen asennetutkimuksen näkökulmaa. Haastatteluaineistosta selvisi, että haastateltujen liikuntaa koskevat asenteet ovat joko säilyneet myönteisinä tai parantuneet. Merkittävä enemmistö haastatteluvirikkeisiin saaduista responsseista oli sävyltään positiivisia, tosin varauksellisiakin kommentteja ilmeni. Innostuneimman vastaanoton saivat mm. viesti siitä, että vähäkin liikkeen lisääminen on parempi kuin ei mitään, liikuntakokeilut, ”SMART”-tavoitteen asettelun ja suunnittelun taidot sekä uusi tieto istumisen vähentämisen haitoista. Vaikka joidenkin opiskelijoiden puheessa ilmeni tulkinta, että interventio oli vaikuttanut sekä ajatuksiin että arjen liikkumiseen, osa ei kokenut intervention tavoitteiden siirtyneen käytännöksi. Käsittelemme tällaisen lähestymistavan mahdollisuuksia ja haasteita interventioevaluaatiossa. Avainsanat: interventiouskollisuus, vastaanottotutkimus, nuoret, laadullinen asennetutkimusPeer reviewe

Men with Crohn's disease may have an increased risk for head and neck squamous cell carcinoma - a nationwide register study

Objective Our goal was to study inflammatory bowel disease (IBD) patients' risk of head and neck squamous cell carcinoma (HNSCC), compared to general population.Materials and methods We performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort's complementary age-year-sex-person-year incidence to that of the whole Finnish population.Results About 70,567 patients were diagnosed with IBD (Crohn's disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065-1.614, P = 0.062). When calculating Crohn's disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn's disease (SIR 1.951, 95% CI 1.216-2.935, P = 0.025).Conclusion An increased risk for HNSCC was found in men with Crohn's disease compared to the Finnish population expectations.Clinical relevance This study provides information that would improve follow-up protocols and treatment guidelines of IBD.</p

Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma

Neuroblastoma is a neural crest-derived childhood tumor of the peripheral nervous system in which MycN amplification is a hallmark of poor prognosis. Here we show that MycN is expressed together with phosphorylation-stabilizing factor CIP2A in regions of the neural plate destined to form the CNS, but MycN is excluded from the neighboring neural crest stem cell domain. Interestingly, ectopic expression of MycN or CIP2A in the neural crest domain biases cells toward CNS-like neural stem cells that express Sox2. Consistent with this, some forms of neuroblastoma have been shown to share transcriptional resemblance with CNS neural stem cells. As high MycN/CIP2A levels correlate with poor prognosis, we posit that a MycN/CIP2A-mediated cell-fate bias may reflect a possible mechanism underlying early priming of some aggressive forms of neuroblastoma. In contrast to MycN, its paralogue cMyc is normally expressed in the neural crest stem cell domain and typically is associated with better overall survival in clinical neuroblastoma, perhaps reflecting a more “normal” neural crest-like state. These data suggest that priming for some forms of aggressive neuroblastoma may occur before neural crest emigration from the CNS and well before sympathoadrenal specification

Population-Based Assessment of Contact Tracing Operations for Coronavirus Disease 2019 in Pirkanmaa Hospital District, Finland

Background: The coronavirus disease 2019 (COVID-19) epidemic overwhelmed local contact tracing (CT) efforts in many countries. In Finland, severe acute respiratory syndrome coronavirus 2 incidence and mortality were among the lowest in Europe during 2020-2021. We evaluated CT efficiency, effectiveness, and transmission settings. Methods: Polymerase chain reaction (PCR) test-positive COVID-19 cases and high-risk contacts in the population-based CT database of Pirkanmaa Hospital District (population 540 000) during June 2020-May 2021 were interviewed. Results: Altogether 353 926 PCR tests yielded 4739 (1.3%) confirmed cases (average 14-day case notification rate, 34 per 100 000 population); about 99% of confirmed cases and high-risk contacts were reached by a CT team. Of 26 881 high-risk contacts who were placed in quarantine, 2275 subsequently tested positive (48% of new cases), 825 (17%) had been in quarantine ≥48 hours before symptoms, and 3469 (77%) of locally acquired cases were part of transmission chains with an identified setting. The highest secondary attack rates were seen in households (31%), healthcare patients (18%), and private functions (10%). Among the 311 hospitalized patients, COVID-19 diagnosis or exposure was known in 273 (88%) before emergency room admission (identified patients). Healthcare workers had the highest proportion of work-related infections (159 cases [35%]). The source of infection was classifiable in 65% and was most commonly a coworker (64 cases [62%]). Conclusions: Our data demonstrate the role of effective testing and CT implementation during the cluster phase of COVID-19 spread. Although half of newly diagnosed cases were already in quarantine, targeted public health measures were needed to control transmission. CT effectiveness during widespread community transmission should be assessed.publishedVersionPeer reviewe

Erikoislääkärikouluttajien valmennuksen ABC - yleislääketieteen malli

Vertaisarvioitu.Yleislääketieteen erikoislääkärikouluttajien koulutusta tai valmennusta on järjestetty 1980-luvulta lähtien. Toiminta on ollut koko Suomessa samankaltaista ja järjestelmällistä 2010-luvun alusta. Kurssimuotoisen valmennuksen ytimessä ovat vaikuttaviksi havaitut elementit: teorian ja käytännön ohjaustyön jatkuva vuoropuhelu, monipuoliset harjoitukset, keskustelut, käytännönläheiset ennakko- ja välitehtävät sekä reflektio. Palaute on olennaista harjoituksissa ja välitehtävissä. Valmennusta kehitetään ja muokataan vastaamaan erikoistujien, tulevien kouluttajien ja palvelujärjestelmän tarpeita. Erikoislääkärikouluttajat ovat merkittävä voimavara perusterveydenhuollon palvelutuotannon laadun varmistamisessa, sillä noin puolet terveyskeskusten lääkäreistä suorittaa jotain koulutusvaihetta

Erikoislääkärikouluttajien valmennuksen ABC - yleislääketieteen malli

publishedVersio