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  • Heuser, Vanina D.; Mansuri, Naziha; Mogg, Jasper; Kurki, Samu; Repo, Heli; Kronqvist, Pauliina; Carpen, Olli; Gardberg, Maria (2018)
    Basal-like breast cancer is an aggressive form of breast cancer with limited treatment options. The subgroup can be identified immunohistochemically, by lack of hormone receptor expression combined with expression of basal markers such as CK5/6 and/or epidermal growth factor receptor (EGFR). In vitro, several regulators of the actin cytoskeleton are essential for efficient invasion of basal-like breast cancer cell lines. Whether these proteins are expressed in vivo determines the applicability of these findings in clinical settings. The actin-regulating formin protein FHOD1 participates in invasion of the triple-negative breast cancer cell line MDA-MB-231. Here, we measure the expression of FHOD1 protein in clinical triple-negative breast cancers by using immunohistochemistry and further characterize the expression of another formin protein, INF2. We report that basal-like breast cancers frequently overexpress formin proteins FHOD1 and INF2. In cell studies using basal-like breast cancer cell lines, we show that knockdown of FHOD1 or INF2 interferes with very similar processes: maintenance of cell shape, migration, invasion, and proliferation. Inhibition of EGFR, PI3K, or mitogen-activated protein kinase activity does not alter the expression of FHOD1 and INF2 in these cell lines. We conclude that the experimental studies on these formins have implications in the clinical behavior of basal-like breast cancer.
  • Järvinen, Tommi; Ilonen, Ilkka; Kauppi, Juha; Volmonen, Kirsi; Salo, Jarmo; Räsänen, Jari (2018)
    Background Methods In esophageal cancer, nutritional challenges are extremely common. Malignant obstruction resulting from esophageal cancer (EC) is often treated by the insertion of expandable stents, but little is known as to the role and evolution of sarcopenia in this patient population. The aim of this article was to determine the effects of body mass parameters on survival of advanced EC patients who received a stent for palliation of malignant obstruction. This was a retrospective observational study of 238 EC patients who had a stent inserted for palliation of malignant obstruction between 2005 and 2013. Skeletal muscle mass was calculated from abdominal computed tomography scans, and the patients were divided into sarcopenic and non-sarcopenic groups. A follow-up computed tomography scan was available in 118 patients. The primary outcome was survival, and complication rates and the need for an alternative enteral feeding route were secondary outcomes. Results Conclusions Sarcopenia occurred in 199 (85%) patients. Median survival was 146 (range: 76-226) days in the sarcopenia group and 152 (range: 71-249) days in the non-sarcopenic group (P = 0.61). Complication rates between the groups were not significantly different (P = 0.85). In Cox regression analysis, the skeletal muscle index was inversely correlated with overall survival (hazard ratio 0.98, 95% confidence interval 0.97-0.99; P = 0.033). Sarcopenia, defined by consensus thresholds, at the time of stent insertion cannot effectively predict poor survival in this patient cohort, but a lower skeletal muscle index correlates with poor prognosis as a continuous variable.
  • Sadeghi, Mohammadreza; Wang, Yilin; Ramqvist, Torbjorn; Aaltonen, Leena-Maija; Pyöriä, Lari; Toppinen, Mari; Soderlund-Venermo, Maria; Hedman, Klaus (2017)
    Background: In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections with human polyomaviruses (HPyVs) occur since childhood and the viruses are widespread in the general population. However, the viral persistence sites and transmission routes are by and large unknown. Our previous studies demonstrated that the four new HPyVs KIPyV, WUPyV, MCPyV and TSPyV were present in the tonsils, and suggested lymphoid tissue as a persistent site of these emerging human viruses. We developed a Luminex-based multiplex assay for simultaneous detection of all 13 HPyVs known, and explored their occurrence in tonsillar tissues of children and adults mostly with tonsillitis or tonsillar hypertrophy. Methods: We set up and validated a new Luminex-based multiplex assay by using primer pairs and probes targeting the respective HPyV viral protein 1 (VP1) genes. With this assay we tested 78 tonsillar tissues for DNAs of 13 HPyVs. Results: The multiplex assay allowed for simultaneous detection of 13 HPyVs with high analytical sensitivity and specificity, with detection limits of 10(0)-10(2) copies per microliter, and identified correctly all 13 target sequences with no cross reactions. HPyV DNA altogether was found in 14 (17.9%) of 78 tonsils. The most prevalent HPyVs were HPyV6 (7.7%), TSPyV (3.8%) and WUPyV (3.8%). Mixed infection of two HPyVs occurred in one sample. Conclusions: The Luminex-based HPyV multiplex assay appears highly suitable for clinical diagnostic purposes and large-scale epidemiological studies. Additional evidence was acquired that the lymphoid system plays a role in HPyV infection and persistence. Thereby, shedding from this site during reactivation might take part in transmission of the newly found HPyVs.
  • Orell, Helena; Schwab, Ursula; Saarilahti, Kauko; Österlund, Pia; Ravasco, Paula; Mäkitie, Antti (2019)
    Background: Head and neck cancer and its treatment may deteriorate nutrition status. Previous data have shown that intensive nutrition intervention by a dietician reduces radiation-induced adverse events including weight loss. Objective: To determine if on-demand nutrition counselling (ODC) would be as effective as intensive nutrition counselling (INC) in patients undergoing (chemo)radiotherapy. Methods: Fifty-eight patients were randomly assigned to receive INC (n=26) or ODC (n=32). Outcome measures were nutrition status (PG-SGA), weight loss, handgrip strength (HGS), body composition and survival. Results: Weight loss and impaired nutrition parameters during oncological treatment were seen equally in both groups (NS). Leaner patients at baseline maintained their weight, while overweight patients lost both weight and handgrip strength during treatment. Disease- free survival (DFS) (median=43 months) was not affected by weight loss during treatment. Lower baseline HGS and malnutrition were associated with worse DFS (low vs. normal HGS: 15 vs. 42 months; p=0.05 and malnutrition vs. good nutrition status: 17 vs. 42 months; p=0.014, respectively). Survival according to low vs. normal HGS in the INC group was 4 vs. 44 months (p=0.007) and in the ODC group 28 vs. 40 months (p=0.944). According to malnutrition vs. good nutrition status in the INC group, DFS was 21 vs. 43 months (p=0.025) and in the ODC group 15 vs. 41 months (p=0.03). Conclusions: Individualised on-demand nutrition counselling was as efficient as intensive counselling during (chemo)radiotherapy. Overweight patients had more severe weight loss but not poorer survival. Low HGS and malnutrition at baseline were directly associated with poor survival.
  • Hassona, Y.; Scully, C.; Almangush, A.; Baqain, Z.; Sawair, F. (2014)
  • Halava, Heli; Huupponen, Risto; Pentti, Jaana; Kivimaki, Mika; Vahtera, Jussi (2016)
    BACKGROUND: The discontinuation of statin medication is associated with an increased risk of cardiovascular and cerebrovascular events and, among high-risk patients, all-cause mortality, but the reasons for discontinuation among statin initiators in clinical practice are poorly understood. OBJECTIVE: To examine factors predicting the early discontinuation of statin therapy. METHODS: In this prospective cohort study, participants with baseline measurements before the initiation of statin treatment were linked to national registers and followed for the discontinuation of statins during the first year of treatment (no filled prescriptions after statin initiation within the subsequent 12 months). RESULTS: Of all the 9285 statin initiators, 12% (n = 1142) were discontinuers. Obesity, overweight, vascular comorbidities, and older age were independently associated with a reduced risk of discontinuation [odds ratios (OR) = 0.82 (95% confidence interval [CI], 0.69-0.99), 0.85 (95% CI, 0.73-0.98), 0.80 (95% CI, 0.68-0.93), and 0.82 (95% CI, 0.68-0.99), respectively]. In contrast, high-patient cost-sharing was associated with an increased odds (OR = 1.29; 95% CI, 1.03-1.62) for discontinuation. The only significant difference between the sexes (P = .002) was observed among the participants with risky alcohol use, which was associated with a decreased odds for discontinuation among the men (OR = 0.69; 95% CI, 0.49-0.98) and an increased odds among the women (OR = 1.28; 95% CI, 1.02-1.62). CONCLUSIONS: The discontinuation of statin therapy during the first year after initiation is common. Lowering out-of-pocket expenditures and focusing on low-risk patient groups and women with risky alcohol use could help maintain the continuation of medication. (C) 2016 National Lipid Association. This is an open access article under the CC BY license (
  • Laurell, Katarina; Artto, Ville; Bendtsen, Lars; Hagen, Knut; Haggstrom, Johan; Linde, Mattias; Soderstrom, Lars; Tronvik, Erling; Wessman, Maija; Zwart, John Anker; Kallela, Mikko (2016)
    Aim To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors. Methods In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%. Results Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% (p Conclusion PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.
  • Hukkinen, Maria; Mutanen, Annika; Pakarinen, Mikko P. (2017)
    Background. Liver disease occurs frequently in short bowel syndrome. Whether small bowel dilation in short bowel syndrome could influence the risk of liver injury through increased bacterial translocation remains unknown. Our aim was to analyze associations between small bowel dilation, mucosal damage, bloodstream infections, and liver injury in short bowel syndrome patients. Methods. Among short bowel syndrome children (n = 50), maximal small bowel diameter was measured in contrast series and expressed as the ratio to the height of the fifth lumbar vertebra (small bowel diameter ratio), and correlated retrospectively to fecal calprotectin and plasma citrulline respective markers of mucosal inflammation and mass bloodstream infections, liver biochemistry, and liver histology. Results. Patients with pathologic small bowel diameter ratio > 2.17 had increased fecal calprotectin and decreased citrulline (P <.04 each). Of 33 bloodstream infections observed during treatment with parenteral nutrition, 16 were caused by intestinal bacteria, cultured 15 times more frequently when small bowel diameter ratio was >2.17 (P <.001). Intestinal bloodstream infections were predicted by small bowel diameter ratio (odds ratio 1.88, P = .017), and their frequency decreased after operative tapering procedures (P = .041). Plasma bilirubin concentration, gamma-glutamyl transferase activity, and histologic grade of cholestasis correlated with small bowel diameter ratio (0.356-0.534, P <.014 each), and were greater in the presence of intestinal bloodstream infections (P <.001 for all). Bloodstream infections associated with portal inflammation, cholestasis, and fibrosis grades (P <.031 for each). In linear regression, histologic cholestasis was predicted by intestinal bloodstream infections, small bowel diameter ratio, and parenteral nutrition (beta = 0.36-1.29; P <.014 each), while portal inflammation by intestinal bloodstream infections only (beta = 0.62; P = .033). Conclusion. In children with short bowel syndrome, small bowel dilation correlates with mucosal damage, bloodstream infections of intestinal origin, and cholestatic liver injury. In addition to parenteral nutrition, small bowel dilation and intestinal bloodstream infections contribute to development of short bowel syndrome-associated liver disease.