Browsing by Subject "Carcinoma"

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  • Heikkinen, Ilkka (Helsingin yliopisto, 2018)
    Johdanto: : Sekuriini on proteiini, jolla on tärkeä merkitys solujen jakautumisessa. Sen pääasiallinen tehtävä on estää mitoosin aikana sisarkromatidien ennenaikainen irtoaminen toisistaan ennen kuin tumasukkulan muodostuminen on valmis. Sekuriini säätelee myös M-faasiin siirtymistä ja p53 proteiinin toimintaa, sekä osallistuu DNA:n korjausprosessiin. Sekuriinilla on todettu olevan merkittävä rooli myös useiden syöpien kehittymisessä. Tässä tutkimuksessa analysoimme sekuriinin tuotannon yhteyttä liikkuvan kielen levyepiteelikarsinoomapotilaiden ennusteeseen. Menetelmät: Tutkimusaineisto koostui 93 kielisyöpäpotilaasta, joiden diagnoosi sekä hoito toteutettiin Helsingin yliopistollisessa keskussairaalassa sekä Oulun yliopistollisessa sairaalassa vuosina 1981-2005. Sekuriinituotannon määrää ja sijaintia syöpäkudoksessa tutkittiin immunohistokemiallisesti siten, että 52 potilaan tissue microarray (TMA) ja 41 potilaan kasvainresekaattien histologiset leikkeet värjättiin monoklonaalisella sekuriini vasta-aineella. Sekuriinin määrää arvioitiin prosentuaalisena osuutena positiivisesti sekuriinivasta-aineella värjäytyneistä syöpäsoluista suhteessa kaikkiin kentässä näkyviin syöpäsoluihin. Tilastollisista analyyseistä khiin neliö -testiä käytettiin eri muuttujien välisten riippuvuuksien vertailussa. Kaplan-Meier kuvaajaa, log-rank testiä ja Coxin suhteellisen vaaran mallia sovellettiin elinaika-analyysissä. Tilastolliset analyysit tehtiin IBM SPSS (versio 20.0) tilastoanalyysiohjelmistolla. Tulokset: Sekuriinin yliekspressio liittyi merkittävästi syövän erilaistumisasteeseen (P=0.03). Sekuriinia oli enemmän levinneisyysasteeltaan pidemmälle edenneissä syövissä (asteet III ja IV), mutta tämä yhteys ei ollut tilastollisesti merkitsevä. Assosiaatiota ei myöskään löytynyt sekuriinin määrän ja kielisyöpäkuolleisuuden tai kielisyövän uusiutumisen välillä (P > 0.05). Johtopäätökset: Löydöksemme viittaavat siihen, että sekuriinin yliekspressiolla saattaa olla merkitystä kielisyövän etenemisessä, mutta sekuriini ei ennusta kielisyöpäpotilaan kuolleisuutta tautiin tai taudin uusiutumistaipumusta.
  • Cândido, Marcus Vinicius; Syrjä, Pernillä; Hanifeh, Mohsen; Lepajõe, Jaan; Salla, Kati; Kilpinen, Susanne; Noble, Peter-John Mäntylä; Spillmann, Thomas (2021)
    Gastric carcinoma (GC) is uncommon in dogs, except in predisposed breeds such as Belgian Shepherd dogs (BSD) of the Tervuren and Groenendael varieties. When GC is diagnosed in dogs it is often late in the disease, resulting in a poorer prognosis. The aim of this prospective clinical study was to investigate possible associations of gastric mucosal pathologies with clinical signs, laboratory test results and GC in BSD. An online survey gathered epidemiological data to generate potential risk factors for vomiting as the predominant gastric clinical sign, and supported patient recruitment for endoscopy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) score and signs of gastroesophageal reflux (GER) were used to allocate BSD older than five years to either Group A, with signs of gastric disease, or Group B, without signs. Findings in the clinical history, laboratory tests and gastric histopathology of endoscopic biopsies were statistically analysed in search of associations.
  • Cândido, Marcus V.; Syrjä, Pernilla; Hanifeh, Mohsen; Lepajõe, Jaan; Salla, Kati; Kilpinen, Susanne; Noble, Peter-John M; Spillmann, Thomas (BioMed Central, 2021)
    Abstract Background Gastric carcinoma (GC) is uncommon in dogs, except in predisposed breeds such as Belgian Shepherd dogs (BSD) of the Tervuren and Groenendael varieties. When GC is diagnosed in dogs it is often late in the disease, resulting in a poorer prognosis. The aim of this prospective clinical study was to investigate possible associations of gastric mucosal pathologies with clinical signs, laboratory test results and GC in BSD. An online survey gathered epidemiological data to generate potential risk factors for vomiting as the predominant gastric clinical sign, and supported patient recruitment for endoscopy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) score and signs of gastroesophageal reflux (GER) were used to allocate BSD older than five years to either Group A, with signs of gastric disease, or Group B, without signs. Findings in the clinical history, laboratory tests and gastric histopathology of endoscopic biopsies were statistically analysed in search of associations. Results The online survey included 232 responses. Logistic regression analysis recognized an association of vomiting with gagging, poor appetite and change in attitude. Recruitment for endoscopy included 16 BSD in Group A (mean age 9.1 ± 1.8 years, mean CCECAI = 3.1 ± 2.2 and signs of GER); and 11 in Group B (mean age 9.8 ± 1.4 years, CCECAI = 0, no signs of GER). Seven (25.9%) of the 27 BSD (Group A 4/16, Group B 3/11) had leukopenia. Serum C-reactive protein tended to be increased with more advanced GC (P = 0.063). Frequency of GC, mucosal atrophy, mucous metaplasia, or glandular dysplasia did not differ between groups. GC was frequently diagnosed (6/27), even without clinical signs (2/11). The odds ratio for vomiting (OR = 9.9; P = 0.016) was increased only when glandular dysplasia was present. GC was associated with mucous metaplasia (P = 0.024) and glandular dysplasia (P = 0.006), but not with mucosal atrophy (P = 1). Conclusions GC can develop as an occult disease, associated with metaplasia and dysplasia of the gastric mucosa. Suggestive clinical signs, notably vomiting, should warrant timely endoscopy in BSD. Extensive endoscopic screening of asymptomatic dogs remains, however, unrealistic. Therefore, biomarkers of mucosal pathology preceding clinical illness are needed to support an indication for endoscopy and enable early diagnosis of GC.
  • Meretoja, Tuomo; Heikkilä, Päivi; Hukkinen, Katja; Leidenius, Marjut (2018)
  • Randen-Brady, Reija; Carpen, Timo; Jouhi, Lauri; Syrjänen, Stina; Haglund, Caj; Tarkkanen, Jussi; Remes, Satu; Mäkitie, Antti; Mattila, Petri S.; Silen, Suvi; Hagström, Jaana (2019)
    Current human papillomavirus (HPV) detection methods in oropharyngeal squamous cell carcinoma (OPSCC) have varying sensitivity and specificity. We aimed to compare different HPV-detection methods against the test used in clinical practice, ie, p16 immunohistochemistry (IHC) and to evaluate whether another HPV-detection test additional to p16 IHC would be worthwhile in OPSCC specimens. The study cohort comprised 357 consecutive OPSCC patients during two time periods: 2000-2009 and 2012-2016. From tumor tissue slides, HPV mRNA via in situ hybridization (ISH), HPV DNA via ISH and HPV DNA via polymerase chain reaction (PCR) were detected. The results of these methods were compared with p16 IHC results. Additionally, clinicopathological factors were compared with the methods studied. The sensitivity of HPV mRNA ISH, HPV DNA ISH and HPV DNA PCR were 93.4%, 86.3%, and 83.5%, respectively. The corresponding specificity was 92.4%, 95.3%, and 89.1%, respectively. The negative predictive value for p16 IHC was highest (89.0%) when using mRNA ISH, and followed by DNA ISH (83.5%). ISH for high-risk HPV E6/E7 mRNA was found to be a highly specific and sensitive method for detecting HPV in OPSCC. As p16 protein may be overexpressed due to HPV-independent mechanisms, all p16 IHC positive OPSCCs should be considered for retesting using mRNA ISH in order to verify transcriptionally active HPV. This is especially critical when considering de-escalated treatment approaches for patients with HPV-positive tumors and still maintaining favorable outcomes for this subgroup of patients. (C) 2019 Elsevier Inc. All rights reserved.
  • Heikkilä, Nelli; Kekäläinen, Eliisa (2020)
    Kateenkorva on primaarinen immunologinen elin, jossa kehittyvät T-solut, hankinnaisen immuunijärjestelmän keskeiset toimijat ja säätelijät. Kateenkorvan tärkeyttä heijastaa se, että kateenkorvan synnynnäinen puuttuminen ilmenee kehittyneistä hoidoista huolimatta usein kuolemaan johtavana vaikeana immuunipuutoksena. Tästä huolimatta tietämyksemme ihmisen kateenkorvan toiminnasta on rajoittunutta ja pohjautuu pääosin hiirimalleihin. Kateenkorvan hankinnaiset sairaudet ovat harvinaisia, ja niiden kliininen fenotyyppi on hyvin vaihteleva. Näistä tavallisin on kateenkorvan neoplasia eli tymooma ja siihen paraneoplastisena ilmiönä liittyvät erilaiset autoimmuuni-ilmentymät.
  • Jouhi, Lauri; Atula, Timo; Mäkitie, Antti; Keski-Santti, Harri (2019)
    PurposeOnly a minority of patients with oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed without regional metastasis (cN0). Studies focusing on the management of cN0 neck in OPSCC are scarce.MethodsWe reviewed all OPSCC patients treated at our institution with cN0 neck between 2000 and 2009. The treatment of neck and pattern of regional control was analyzed. Median follow-up was 5years (range 3.5-9.0) or until death.ResultsOf the total 313 OPSCC patients treated within the period, 56 (18%) presented with cN0 neck. Of them, 51 (91%) received completed treatment with curative intent: 46 (90%) underwent elective neck treatment with either neck dissection (chemo)radiotherapy (C)RT (n=23) or (C)RT (n=23). A regional recurrence occurred in three patients (6%) and they all had a p16-negative soft palate midline primary tumor. Two of these patients had received RT on the neck.Conclusions While the overall prognosis of OPSCC is generally favorable and regional recurrences are infrequent, soft palate tumors, that are usually p16 negative, may form an subgroup warranting more aggressive treatment despite the clinical appearance of early stage.
  • Sundquist, Elias; Renko, Outi; Salo, Sirpa; Magga, Johanna; Cervigne, Nilva K.; Nyberg, Pia; Risteli, Juha; Sormunen, Raija; Vuolteenaho, Olli; Zandonadi, Flavia; Leme, Adriana F. Paes; Coletta, Ricardo D.; Ruskoaho, Heikki; Salo, Tuula (2016)
    The invasion of carcinoma cells is a crucial feature in carcinogenesis. The penetration efficiency not only depends on the cancer cells, but also on the composition of the tumor microenvironment. Our group has developed a 3D invasion assay based on human uterine leiomyoma tissue. Here we tested whether human, porcine, mouse or rat hearts as well as porcine tongue tissues could be similarly used to study carcinoma cell invasion in vitro. Three invasive human oral tongue squamous cell carcinoma (HSC-3, SCC-25 and SCC-15), melanoma (G-361) and ductal breast adenocarcinoma (MDA-MB-231) cell lines, and co-cultures of HSC-3 and carcinoma-associated or normal oral fibroblasts were assayed. Myoma tissue, both native and lyophilized, promoted invasion and growth of the cancer cells. However, the healthy heart or tongue matrices were unable to induce the invasion of any type of cancer cells tested. Moreover, when studied in more detail, small molecular weight fragments derived from heart tissue rinsing media inhibited HSC-3 horizontal migration. Proteome analysis of myoma rinsing media, on the other hand, revealed migration enhancing factors. These results highlight the important role of matrix composition for cancer invasion studies in vitro and further demonstrate the unique properties of human myoma organotypic model. (C) 2016 Elsevier Inc. All rights reserved.
  • Jouhi, Lauri; Mohamed, Hesham; Makitie, Antti; Remes, Satu Maria; Haglund, Caj; Atula, Timo; Hagstrom, Jaana (2017)
    A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
  • Mäkitie, Antti; Tuokkola, Iida; Laurell, Göran; Mäkitie, Outi; Olsen, Kerry; Takes, Robert P.; Florek, Ewa; Szyfter, Krzysztof; Sier, Cornelis F. M.; Ferlito, Alfio (2021)
    Purpose of review Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. Recent findings The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.