Current Issue : July - September Volume : 2014 Issue Number : 3 Articles : 7 Articles
Background: The aim of this study was to examine breast density in relation to breast cancer specific survival and\r\nto assess if this potential association was modified by mode of detection. An additional aim was to study whether\r\nthe established association between mode of detection and survival is modified by breast density.\r\nMethods: The study included 619 cases from a prospective cohort, The Malm�¶ Diet and Cancer Study. Breast density\r\nestimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women,\r\nusing Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in\r\nseveral steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status,\r\nbody mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of\r\ndetection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR\r\nfollowing different adjustments were analyzed by Freedmans%.\r\nResults: After adjustment for age and other prognostic factors, women with dense, as compared to fatty\r\nbreasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over\r\ndensity categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR\r\n2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a\r\nhigher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph\r\nnodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between\r\nnon-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change.\r\nConclusions: High breast density at diagnosis may be associated with decreased breast cancer survival. This\r\nassociation appears to be stronger in women with symptomatic cancers but breast density could not explain\r\ndifferences in survival according to detection mode...
Background: Approximately 30% of breast tumors do not express the estrogen receptor (ER) a, which is necessary\r\nfor endocrine therapy approaches. Studies are ongoing in order to restore ERa expression in ERa-negative breast\r\ncancer. The aim of the present study was to determine if calcitriol induces ERa expression in ER-negative breast\r\ncancer cells, thus restoring antiestrogen responses.\r\nMethods: Cultured cells derived from ERa-negative breast tumors and an ERa-negative breast cancer cell line\r\n(SUM-229PE) were treated with calcitriol and ERa expression was assessed by real time PCR and western blots. The\r\nERa functionality was evaluated by prolactin gene expression analysis. In addition, the effects of antiestrogens were\r\nassessed by growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and Ether-� -go-go 1 (EAG1)\r\nwas also evaluated in cells treated with calcitriol alone or in combination with estradiol or ICI-182,780. Statistical\r\nanalyses were determined by one-way ANOVA.\r\nResults: Calcitriol was able to induce the expression of a functional ERa in ER-negative breast cancer cells. This\r\neffect was mediated through the vitamin D receptor (VDR), since it was abrogated by a VDR antagonist. Interestingly,\r\nthe calcitriol-induced ERa restored the response to antiestrogens by inhibiting cell proliferation. In addition,\r\ncalcitriol-treated cells in the presence of ICI-182,780 resulted in a significant reduction of two important cell\r\nproliferation regulators CCND1 and EAG1.\r\nConclusions: Calcitriol induced the expression of ERa and restored the response to antiestrogens in ERa-negative\r\nbreast cancer cells. The combined treatment with calcitriol and antiestrogens could represent a new therapeutic\r\nstrategy in ERa-negative breast cancer patients....
Background: Identification of factors associated with work disability in cancer survivors on long term sick leave\r\nmay support these survivors in choosing effective measures to facilitate vocational rehabilitation and return to work.\r\nTherefore, this study aims to disclose factors associated with work disability in cancer survivors at 24 months of sick\r\nleave.\r\nMethods: A cross sectional study was conducted. The study population consisted of employed sick-listed cancer\r\nsurvivors, aged between 18 and 64 years. They received a questionnaire at 24-month sick leave, the maximum\r\nperiod of sick leave allowed by Dutch social security legislation. Data were linked with the outcome of work\r\ndisability assessment, as performed by the Dutch social security agency. A hierarchical multivariate logistic\r\nregression analysis was performed to identify factors associated with work disability.\r\nResults: Data of 351 valid cases were analysed. The multivariate analysis showed that, for cancer survivors at\r\n24-month sick leave, Dutch nationality, higher education, receiving hormone therapy, metastatic disease, physical\r\nlimitations and low self-reported work ability were associated with an increased risk for work disability.\r\nConclusions: This study identified factors associated with work disability of employed cancer survivors at\r\n24 months of sick leave. The results of the current study may serve as a starting point to investigate the course of\r\nwork disability beyond the maximum period of 24 months of sick leave. In order to enhance work participation of\r\ncancer survivors beyond this term, prospective data on work disability in the Netherlands are required....
Background: Impairment of cognitive functioning has been reported in several studies in patients treated with\r\nchemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor\r\nreceptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive\r\nfunction of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI).\r\nMethods: Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal\r\ncell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients\r\nwith mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen\r\nneuropsychological tests examining the main cognitive domains (intelligence, memory, attention and\r\nconcentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four\r\nquestionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing.\r\nResults: No significant differences in mean age, sex distribution, education level or IQ were found between the\r\nthree groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and\r\nExecutive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the\r\nVEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive\r\ndysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions,\r\ncompared to patient controls. Both patients groups performed on the domain Attention & Concentration the same\r\nas the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working\r\nMemory tasks.\r\nConclusions: Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning,\r\nspecifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with\r\nVEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment.\r\nTrial registration: ClinicalTrials.gov Identifier: NCT01246843....
Background: Gallbladder cancer is the most frequent malignancy of the bile duct with high aggressive and extremely\r\npoor prognosis. The main objective of the paper was to investigate the inhibitory effects of oridonin, a diterpenoid\r\nisolated from Rabdosia rubescens, on gallbladder cancer both in vitro and in vivo and to explore the mechanisms\r\nunderlying oridonin-induced apoptosis and cell cycle arrest.\r\nMethods: The anti-tumor activity of oridonin on SGC996 and NOZ cells was assessed by the MTT and colony forming\r\nassays. Cell cycle changes were detected by flow cytometric analysis. Apoptosis was detected by annexin V/PI\r\ndouble-staining and Hoechst 33342 staining assays. Loss of mitochondrial membrane potential was observed by\r\nRhodamine 123 staining. The in vivo efficacy of oridonin was evaluated using a NOZ xenograft model in athymic\r\nnude mice. The expression of cell cycle- and apoptosis-related proteins in vitro and in vivo was analyzed by western blot\r\nanalysis. Activation of caspases (caspase-3, -8 and -9) was measured by caspases activity assay.\r\nResults: Oridonin induced potent growth inhibition, S-phase arrest, apoptosis, and colony-forming inhibition in SGC996\r\nand NOZ cells in a dose-dependent manner. Intraperitoneal injection of oridonin (5, 10, or 15 mg/kg) for 3 weeks\r\nsignificantly inhibited the growth of NOZ xenografts in athymic nude mice. We demonstrated that oridonin\r\nregulated cell cycle-related proteins in response to S-phase arrest by western blot analysis. In contrast, we\r\nobserved inhibition of NF-?B nuclear translocation and an increase Bax/Bcl-2 ratio accompanied by activated\r\ncaspase-3, caspase-9 and PARP-1 cleavage after treatment with oridonin, which indicate that the mitochondrial\r\npathway is involved in oridonin-mediated apoptosis.\r\nConclusions: Oridonin possesses potent anti-gallbladder cancer activities that correlate with regulation of the\r\nmitochondrial pathway, which is critical for apoptosis and S-phase arrest. Therefore, oridonin has potential as a\r\nnovel anti-tumor therapy for the treatment of gallbladder cancer....
Background: Primary small cell carcinoma of the esophagus (SCCE) is a highly aggressive disease characterized by\r\nearly dissemination and poor prognosis. Because of the rarity of this disease, few previous studies have investigated\r\nthe biomarkers associated with its prognosis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is\r\na stem cell marker and a member of the canonical Wnt-signaling cascade. However, the clinical role of Lgr5 in SCCE\r\nremains unknown.\r\nMethods: Tissue sections were obtained from 44 patients diagnosed with SCCE and expression of Lgr5 was\r\nexamined by immunohistochemistry. The correlations between Lgr5 expression, and clinical parameters and\r\nprognostic significance were evaluated.\r\nResults: Lgr5 was expressed in SCCE cancer tissues. High Lgr5 expression was significantly correlated with lymph\r\nnode metastasis (p = 0.003), late stage (p = 0.003) and unfavorable response to chemotherapy (p = 0.013) according\r\nto RECIST 1.0 criteria. Patients with higher Lgr5 expression levels had shorter overall survival times than those with\r\nlower expression levels.\r\nConclusions: These results demonstrated that overexpression of Lgr5 was significantly correlated with lymph node\r\nmetastasis, tumor stage, and response to chemotherapy. Furthermore, high levels of Lgr5 expression appeared to\r\nbe associated with poorer survival in patients with SCCE....
Background: Recent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression\r\nof different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others.\r\nHowever, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown.\r\nMethods: In this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated\r\nin 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with\r\nmiR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified\r\nusing Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p\r\nregulates the tumour-suppressive effects of klotho in gastric cancer.\r\nResults: In our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues\r\ncompared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric\r\ncancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was\r\nassociated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and\r\nimmunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p.\r\nConclusions: Our present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by\r\ntargeting klotho....
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