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  • Huang, Ying-Lai, 1962, et al. (författare)
  • Mechanical ventilation promotes lung metastasis in experimental 4T1 breast cancer lung-metastasized models
  • 2018
  • Ingår i: Cancer Management and Research. - 1179-1322. ; 10, s. 545-555
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/purpose: The aim of this study was to test the hypothesis that mechanical ventilation (MV) during cancer surgery induces lung stroma/tissue milieu changes, creating a favorable microenvironment for postoperative lung metastatic tumor establishment. Materials and methods: In Protocol A, female BALB/c mice were divided into an MV group and a control (no MV) group, both of which were anesthetized and subjected to intravenous injection of green fluorescent protein (GFP)-labeled mouse mammary carcinoma cell line (4T1) cells. After 24 h, the lung tissue was removed and the number of GFP-labeled 4T1 cells was calculated. In Protocol B, the clinically relevant mouse model of spontaneous breast cancer lung metastasis was used with surgical resection of the primary tumor to investigate the MV event that dictates postoperative lung metastasis. Female BALB/c mice were inoculated in the mammary fat pad with 4T1 cells. After 14-d growth, mice were anesthetized and divided into an MV group and a control (no MV) group during surgical procedures (mastectomy). Metastatic tumor burden was assessed two weeks after mastectomy by both macroscopic metastatic nodule count, hematoxylin–eosin histology, immunohistochemistry for the macrophage marker (CD68), and epithelial cell adhesion molecule (EpCAM). Results: MV was associated with a significant increase in the number of circulating breast tumor cells (GFP-labeled 4T1 cells) remaining in the microvasculature of the lung (P<0.01). Immunohistochemical results showed increased infiltration of CD68-positive macrophages within injured lung parenchyma and metastatic tumor as well as increased expression of EpCAM in metastatic nodules. Postoperative metastases were more prevalent in the mechanically ventilated mice group compared to the non-ventilated group (P<0.05). Conclusion: MV-induced lung metastasis occurs by attracting circulating tumor cells to the site of the lung injury and by accelerating the proliferation of preexisting micro-metastases in the lung. These observations indicate that the metastasis-enhancing effect of MV should be considered in general anesthesia during cancer surgery. © 2018 Huang et al.
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  • Mohlin, Åsa, et al. (författare)
  • Psychological resilience and health-related quality of life in Swedish women with newly diagnosed breast cancer
  • 2020
  • Ingår i: Cancer Management and Research. - 1179-1322. ; 12, s. 12041-12051
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Psychological resilience appears to be an important influencing factor in various aspects of health-related quality of life (HRQoL) in a context of adversity, eg, being informed of a cancer diagnosis. The purpose was to investigate psychological resilience and HRQoL in Swedish women with newly diagnosed breast cancer in relation to demographic and clinicopathological characteristics. Methods: A population-based cross-sectional study was conducted including 517 women with breast cancer in the South Swedish Health Care Region. Participants were enrolled at the time of consultation for the diagnosis. Psychological resilience was assessed with the Connor-Davidson Resilience Scale 25 (CD-RISC25), and HRQoL was assessed with the Short Form Health Survey. The participants responded to questions regarding demographic variables. Clinicopathological data were collected from the Swedish National Quality Register for Breast Cancer. Results: The mean score for psychological resilience was 70.6, identifying 15% of included patients with a score lower than 58 (−1 standard deviation). The study cohort had significantly lower mean scores for several aspects of HRQoL compared with Swedish normative data. Regression analyses demonstrated that psychological resilience was significantly associated with all domains of HRQoL after adjustment for demographic and clinicopathological factors. Conclusion: Higher levels of psychological resilience were significantly related to higher levels of HRQoL in Swedish women with newly diagnosed breast cancer and no modifying factor was identified. The assessment of psychological resilience at the time of breast cancer diagnosis might allow for early identification of women in need of more intense psychosocial support. Future studies are needed to identify a clinically relevant threshold of the CD-RISC25.
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  • Redig, Josefine, et al. (författare)
  • Real-world cost-effectiveness of targeted therapy in metastatic renal cell carcinoma in Sweden : a population-based retrospective analysis
  • 2019
  • Ingår i: Cancer Management and Research. - Auckland : Dove medical press. - 1179-1322. ; 11, s. 1289-1297
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To explore cost-effectiveness of targeted therapies (TTs) in the treatment of metastatic renal cell carcinoma (mRCC) in a real-world context using a nationwide population-based approach.Methods: Data on patients diagnosed with mRCC between 2002 and 2012 were extracted from Swedish national health data registers. To facilitate comparisons of patients diagnosed before and after TT introduction to the market, three cohorts were derived: pre-TT introduction (preTT), patients diagnosed 2002-2005; early TT introduction (TTi), patients diagnosed 2006-2008; and late TT introduction (TTii), which was limited to patients diagnosed 2009-2010 to ensure availability of total health care resource utilization (HCRU) data. Patients were followed until end of 2012. The value of TTs across cohorts was estimated using mean HCRU costs per life-year (LY) gained. Data on HCRU were obtained through national health registers for dispensed medication and inpatient and outpatient care, and the associated costs were estimated using the Lin method to account for censoring. LYs gained were defined as the difference in mean survival over the study period.Results: The preTT, TTi, and TTii cohorts consisted of 1,366, 1,158, and 806 patients, respectively. Mean survival in years from mRCC diagnosis was 1.45 in the preTT cohort, 1.62 in the TTi cohort, and 1.83 in the TTii cohort. The respective mean total HCRU cost per patient over the study period was US$16,894, US$29,922, and US$30,037. The cost per LY gained per cohort was US$78,656 for TTi vs preTT, US$34,132 for TTii vs preTT, and US$523 for TTii vs TTi.Conclusion: Given common willingness-to-pay per LY gained thresholds, this study in a real-world population suggests the use of TTs in the Swedish mRCC population is increasingly cost-effective over time.
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  • Rugwizangoga, Belson, et al. (författare)
  • Experience and Perception of Patients and Healthcare Professionals on Acute Leukemia in Rwanda: A Qualitative Study
  • 2022
  • Ingår i: Cancer Management and Research. - 1179-1322. ; 14, s. 1923-1934
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To explore challenges associated with the timely diagnosis, therapy, and prognosis of acute leukemia in Rwanda. Methods: This is a qualitative study using a phenomenological approach that involved patients, patients' guardians, and healthcare professionals such as physicians from district hospitals and specialists from referral hospitals, as well as healthcare administrators. The primary data were collected from district and referral hospitals and central healthcare administration in Rwanda. The data were collected between July and October 2019. In-depth interviews were conducted, and thematic analysis was employed to interpret the results. Results: We identified barriers to seeking healthcare such as (i) insufficient knowledge within the population may lead patients and their guardians to consult traditional healers before seeking qualified medical care, and (ii) financial constraints that preclude payment of healthcare fees or other out-of-pocket cost related to diagnosis and treatment. We also observed that the referral system is tedious and primary healthcare facilities lack the competence and resources for the necessary diagnostic practices. Both may further delay diagnosis and therapy. Accordingly, healthcare professionals at the referral hospitals stated that most patients were seen at an advanced stage of the disease. For the treatment of acute lymphoblastic leukemia (ALL), only chemotherapy is utilized in Rwanda, while bone marrow (BM) transplantation is not available. Palliation is the only available treatment for the vast majority of Rwandan acute myeloid leukemia (AML) patients. Conclusion: ALL and AML are likely under-reported in Rwanda and diagnosis may be delayed, which may be explained by patient related factors (lack of knowledge, financial constraints), a tedious referral system, and suboptimal diagnostic resources.
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  • Valdimarsson, Valentinus T., et al. (författare)
  • Repeat procedures for recurrent colorectal liver metastases : Analysis of long-term liver regeneration and outcome
  • 2019
  • Ingår i: Cancer Management and Research. - 1179-1322. ; 11, s. 2617-2622
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Repeat hepatectomy is increasingly performed for the management of recurrent colorectal liver metastases (CRLM). The aim of this study was to evaluate longterm functional liver volume (FLV) after a second hepatic procedure and to measure survival outcome. Methods: In this retrospective cohort study, patients treated for recurrent CRLM in the years 2005-2015 at two liver centers were included. Total FLV was calculated before the first procedure and before and after the second procedure. Overall survival was calculated. Results: Eighty-two patients were identified. The median follow-up was 53 (40-71) months from the first procedure. The median interval between first and second procedure was 13 (8-22) months. The initial FLV was 1584 (1313-1927) mL. The FLV was 1438 (1204-1896) mL after the first procedure and 1470 (1172-1699) mL after the second procedure (P<0.001). After the second procedure, a total of ten patients (12%) had a residual liver volume of less than 75% of the initial liver volume. The 5-year overall survival was 37 (26-54)% after the second procedure. Conclusion: Small changes in FLV were found after two hepatic procedures but with considerable inter-individual variation. Patients selected for a repeated hepatic procedure for recurrent CRLM had an acceptable survival.
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  • Yu, Miaomei, et al. (författare)
  • Apolipoprotein M could inhibit growth and metastasis of SMMC7721 cells via vitamin D receptor signaling
  • 2019
  • Ingår i: Cancer Management and Research. - 1179-1322. ; 11, s. 3691-3701
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Apolipoprotein M (ApoM), a member of the apolipoprotein family, is mainly synthesized in the liver, whereas its role in HCC has not been elucidated. Here, we examined the effect of ApoM on the biological behavior of HCC cells and the possible mechanisms. Methods: We used CRISPR/Cas9 technology to knock out ApoM in SMMC7721 cells. Differentially expressed genes before and after ApoM knockout (KO) were analyzed by GeneChip microarrays and confirmed by qRT-PCR. Cell assays of proliferation, apoptosis, migration and invasion were performed in SMMC7721 cells, and the expression of epithelial- mesenchymal transition (EMT) markers was performed by western blot. And we performed functional recovery experiments by overexpressing vitamin D receptor (VDR) in SMMC7721. Results: The ApoM-KO SMMC7721 cell line was successfully constructed using the CRISPR/ Cas9 technology. Our results showed that silencing ApoM suppressed apoptosis and promoted proliferation, migration, invasion and EMT of SMMC7721 cells. The microarray data revealed that a total of 1,868 differentially expressed genes were identified, includingVDR. The qRT-PCR and western blot verification results demonstrated that knocking out ApoM could significantly reduce the expression of VDR. The functional recovery experiments indicated that VDR overexpression could offset the inhibition of cell apoptosis and the promotion of cell proliferation, migration, invasion and EMT caused by knocking out ApoM in SMMC7721 cells. Conclusion: ApoM could function as a tumor suppressor to inhibit the growth and metastasis of SMMC7721 cells via VDR signaling in HCC.
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