| 1. |
- Acuña, Ulyana Muñoz, et al.
(författare)
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Activity in MCF-7 Estrogen-sensitive Breast Cancer Cells of Capsicodendrin from Cinnamosma fragrans
- 2021
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 41:12, s. 5935-5944
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Effect of capsicodendrin on the NF-KB pathway was studied in MCF-7 cancer cells. Materials and Methods: The transcription factor assay was used to screen for NF-KB activity. The effect on IKK beta, ICAM-1, and caspase-7 were studied using western blot. Caspase-1 was studied using Promega Caspase-Glo (R) assay. Reactive oxygen species (ROS) were detected using the fluorescent probe DCFH-DA. The potentiometric dye JC-1 was used to assess mitochondrial membrane potential (Delta psi m) and the cell cycle was examined using a fluorescence-activated cell sorter. Results: NF-kappa B p65 inhibitory effect was IC50=8.6 mu M and cytotoxic activity was IC50=7.5 mu M. The upstream IKK and the downstream ICAM-1 were down-regulated. Sub G1-phase population increased to 81% after 12 h of treatment with capsicodendrin (10 mu M) and there was no loss of Delta psi M. Conclusion: Increased levels of intracellular ROS promoted activity of caspase-1 and induced cell death in MCF-7 cells. Capsicodendrin may be a future anticancer agent that prevents the progression of metastatic breast cancer.
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| 2. |
- Acuña, Ulyana Muñoz, et al.
(författare)
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Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells.
- 2017
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 37:4, s. 1617-1623
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: The survival rate of women diagnosed with triple-negative breast-cancer (TNBC) remains low. Hence, this study aimed at the chemical and biological optimization of furanosteroid derivatives for the treatment of this type of malignancy using TNBC cells.MATERIALS AND METHODS: Semi-synthetic analogs of wortmannolone (1-6) that negatively affected the aberrant pathways in tumor cells were evaluated in hormone-independent breast cancer cells using western blot and cell-cycle analysis.RESULTS: Wortmannolone derivatization generated NF-ĸB inhibitors as new lead structures for further development. Compound (3) was found to be the most significantly active lead.CONCLUSION: Structure-activity analysis in the present study showed that acetylation of the hydroxyl groups and substitution on C3 and C17 of wortmannolone enhanced biological activity. Alpha-substitution of the acetyl group in C3 on ring A (compound 3) resulted in ROS inducing effect; however, presence of an acetyl group in β-position of C3 displayed the highest NF-ĸB p65 inhibitory activity (0.60 μM).
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| 3. |
- Alanazi, Sultan, et al.
(författare)
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Histone Methyltransferase Inhibition Has a Cytotoxic Impact on Transformed Mast Cells : Implications for Mastocytosis
- 2020
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 40:5, s. 2525-2536
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Mast cell transformation, as manifested in mastocytosis, can be a serious condition for which there are limited therapeutic options. Mastocytosis cells can be sensitive to histone deacetylase (HDAC) inhibitors, but their sensitivity to other histone-modifying enzymes has not been assessed. Here we addressed this issue.Materials and Methods: Inhibitors of histone methyl transferases, histone demethylases, histone acetyl transferases and HDACs were tested for their effects on growth, viability, caspase-3 activation and annexin V/DRAQ7 staining in transformed mast cells.Results: Transformed mast cells underwent cell death in response to histone methyl transferase and HDAC inhibition, but were not sensitive to histone demethylase or histone acetyl transferase inhibition. Histone methyl transferase inhibition led to cell death with characteristics of apoptosis, as judged by caspase-3 activation. However, DNA fragmentation was not apparent and Annexin V+/DRAQ7(-) cells were not predominant, suggesting a type of cell death differing from classical apoptosis.Conclusion: Histone methyl transferase inhibition could be developed as a novel regimen for targeting mastocytosis.
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| 4. |
- Almlöv, Karin, et al.
(författare)
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MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer
- 2020
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 40:5, s. 2757-2763
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.
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| 5. |
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| 6. |
- Andreasson, Håkan, et al.
(författare)
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Histopathological classification of pseudomyxoma peritonei and the prognostic importance of PINCH protein
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.MATERIALS AND METHODS: Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.RESULTS: The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).CONCLUSION: The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.
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| 7. |
- Ansari, Daniel, et al.
(författare)
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Centrosomal Abnormalities in Pancreatic Cancer : Molecular Mechanisms and Clinical Implications
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1241-1245
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Forskningsöversikt (refereegranskat)abstract
- The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes. In this review, we summarize recent advances in the understanding of centrosomal aberrations in pancreatic cancer, focusing on regulatory mechanisms and prospects for future anticancer treatment.
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| 8. |
- Ansari, Daniel, et al.
(författare)
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The hippo signaling pathway in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3317-3321
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Forskningsöversikt (refereegranskat)abstract
- Hippo signaling is a key regulator of organ size, tissue hemostasis and regeneration. Dysregulation of the Hippo pathway has been recognized in a variety of human cancers, including pancreatic cancer. YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the two major downstream effectors of the Hippo pathway. YAP and TAZ have been found to promote pancreatic tumor development and progression, even in the absence of mutant Kirsten RAS (KRAS). Pancreatic cancer is associated with an abundant stromal reaction leading to tumor growth and immune escape. It has been found that YAP and TAZ modulate behavior of pancreatic stellate cells and recruitment of tumor-associated macrophages and myeloid-derived suppressor cells. Moreover, YAP and TAZ are associated with chemoresistance and poor prognosis in pancreatic cancer. This review dissects the role of Hippo signaling in pancreatic cancer, focusing on molecular mechanisms and prospects for future intervention.
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| 9. |
- Ansari, Daniel, et al.
(författare)
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The role of PEDF in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3311-3315
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Forskningsöversikt (refereegranskat)abstract
- Pigment epithelium-derived factor (PEDF) is an important antiangiogenic and antitumorigenic factor in a variety of cancer forms, including pancreatic cancer. PEDF is mainly secreted as a soluble monomeric glycoprotein. In human pancreatic cancer PEDF levels are decreased, both in the tissue and serum. The decrease is associated with increased tumor angiogenesis, fibrosis, inflammation, autophagy, occurrence of liver metastasis and worse prognosis. In murine models, loss of PEDF is sufficient to induce invasive carcinoma and this phenotype is associated with large lesions characterized by poor differentiation. Lentiviral gene transfer of PEDF has resulted in decreased microvessel density and has inhibited tumor growth. Herein we review the multifunctional role of PEDF in pancreatic cancer and its therapeutic potential.
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| 10. |
- Antonsson, Andreas, et al.
(författare)
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Induction of apoptosis by staurosporine involves the inhibition of expression of the major cell cycle proteins at the G(2)/m checkpoint accompanied by alterations in Erk and Akt kinase activities
- 2009
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:8, s. 2893-2898
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Staurosporine is a therapeutic agent that inhibits tumor cell growth by inducing cell death via intrinsic apoptotic pathways. Our previous studies in clinical settings have suggested that certain subpopulations of patients with acute myeloid leukemia (AML) had poor response to chemotherapy.MATERIALS AND METHODS: The effect of staurosporine on apoptosis and cell cycle distribution in human leukemic cell line U-937 cells was determined. U-937 cells were treated with staurosporine at 0.5 microM for 18 hours or 1 microM for 24 hours. Analyses of cell cycle distribution and apoptosis were performed using flow cytometric analysis. The effects of staurosporine on the targeted proteins were assessed by immunoblot analysis.RESULTS: A blockade of the cell cycle at the G(2)/M phase was observed in U-937 cells treated with staurosporine. A concomitant induction of apoptosis and activation of caspase-3 in U-937 cells was also achieved. Treatment of U-937 cells with staurosporine at 1 microM for 24 hours, compared with 0.5 microM for 18 hours, appeared to kill the leukemic more efficiently cells and this dose and duration may specifically target p27, Erk and Akt pathways that are important for cancer cell survival and resistance to treatment. We also show that the effects of stauroporine on cell cycle progression and apoptosis in U-937 cells are closely linked.CONCLUSION: Our results suggest that induction of apoptosis and inhibitory proliferation and survival pathways are important events induced by staurosporine. Understanding the conditions under which staurosporine shows high specificity and low toxicity in treatment of leukemic cells is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to chemotherapeutic agents.
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