liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Lotfi, Kourosh
Alternative names
Publications (10 of 52) Show all publications
Kreutzman, A., Yadav, B., Brummendorf, T. H., Gjertsen, B. T., Hee, M. L., Janssen, J., . . . Mustjoki, S. (2019). Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line. Oncoimmunology, 8(9), Article ID e1638210.
Open this publication in new window or tab >>Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line
Show others...
2019 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 9, article id e1638210Article in journal (Refereed) Published
Abstract [en]

Changes in the immune system induced by tyrosine kinase inhibitors (TKI) have been shown to positively correlate with therapy responses in chronic myeloid leukemia (CML). However, only a few longitudinal studies exist and no randomized comparisons between two TKIs have been reported. Therefore, we prospectively analyzed the immune system of newly diagnosed CML patients treated with imatinib (n = 20) or bosutinib (n = 13), that participated in the randomized BFORE trial (NCT02130557). Comprehensive immunophenotyping, plasma protein profiling, and functional assays to determine activation levels of T and NK cells were performed at diagnosis, 3, and 12 months after therapy start. All results were correlated with clinical parameters such as Sokal risk and BCR-ABL load measured according to IS%. At diagnosis, low Sokal risk CML patients had a higher frequency of cytotoxic cells (CD8 + T and NK cells), increased cytotoxic potential of NK cells and lower frequency of naive and central memory CD4 + T cells. Further, soluble plasma protein profile divided patients into two distinct clusters with different disease burden at diagnosis. During treatment, BCR-ABL IS% correlated with immunological parameters such as plasma proteins, together with different memory subsets of CD4+ and CD8 + T cells. Interestingly, the proportion and cytotoxic potential of NK cells together with several soluble proteins increased during imatinib treatment. In contrast, no major immunological changes were observed during bosutinib treatment. In conclusion, imatinib and bosutinib were shown to have differential effects on the immune system in this randomized clinical trial. Increased number and function of NK cells were especially observed during imatinib therapy.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
CML; imatinib; bosutinib; Sokal; BCR-ABL
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-159139 (URN)10.1080/2162402X.2019.1638210 (DOI)000476301700001 ()31428530 (PubMedID)2-s2.0-85069049177 (Scopus ID)
Note

Funding Agencies|Pfizer investigator grant; Finnish Cancer Organizations; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Helsinki Institute of Life Sciences (HiLife); Finnish Cancer Institute

Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-08-23Bibliographically approved
Ingelsson, B., Söderberg, D., Strid, T., Söderberg, A., Bergh, A.-C., Loitto, V.-M., . . . Rosén, A. (2018). Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C. Proceedings of the National Academy of Sciences of the United States of America, 115(3), E478-E487
Open this publication in new window or tab >>Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C
Show others...
2018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 3, p. E478-E487Article in journal (Refereed) Published
Abstract [en]

Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.

Place, publisher, year, edition, pages
Washington, DC, United States: National Academy of Sciences, 2018
Keywords
CpG-C, DAMP, immune DNA sensing, lymphocyte signaling, mitochondrial DNA release
National Category
Basic Medicine Immunology in the medical area
Research subject
Economic Information Systems
Identifiers
urn:nbn:se:liu:diva-144187 (URN)10.1073/pnas.1711950115 (DOI)000423091400018 ()29295921 (PubMedID)2-s2.0-85042104216 (Scopus ID)
Funder
Swedish Cancer Society
Note

Funding agencies: Linkoping Medical Society; Linkoping University; ALF grants; Region Ostergotland, Sweden; Linkoping University Cancer; Ingrid Asp Foundation; Swedish Cancer Society

Available from: 2018-01-09 Created: 2018-01-09 Last updated: 2018-09-07Bibliographically approved
Ilander, M., Olsson-Stromberg, U., Schlums, H., Guilhot, J., Bruck, O., Lahteenmaki, H., . . . Mustjoki, S. (2017). Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia. Leukemia, 31(5), 1108-1116
Open this publication in new window or tab >>Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia
Show others...
2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 5, p. 1108-1116Article in journal (Refereed) Published
Abstract [en]

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naive CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-alpha/IFN-gamma cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-137599 (URN)10.1038/leu.2016.360 (DOI)000400464800009 ()27890936 (PubMedID)
Note

Funding Agencies|Nordic Cancer Union; Finnish Society of Hematology; Biomedicum Helsinki Foundation; Research Foundation of Blood Diseases in Finland; Academy of Finland; Finnish Cancer Organizations; Signe and Ane Gyllenberg Foundation; Finnish Cancer Institute; Doctoral Programme in Clinical Research in the University of Helsinki

Available from: 2017-05-22 Created: 2017-05-22 Last updated: 2018-04-18
Rajala, H. L. M., El Missiry, M., Ruusila, A., Koskenvesa, P., Bruemmendorf, T. H., Gjertsen, B. T., . . . Mustjoki, S. (2017). Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia. Journal of Cancer Research and Clinical Oncology, 143(8), 1543-1554
Open this publication in new window or tab >>Tyrosine kinase inhibitor therapy-induced changes in humoral immunity in patients with chronic myeloid leukemia
Show others...
2017 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 143, no 8, p. 1543-1554Article in journal (Refereed) Published
Abstract [en]

Purpose Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. Methods We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment. Plasma immunoglobulin levels were measured, and different B cell populations in PB and BM were analyzed with flow cytometry. Results Imatinib treatment decreased plasma IgA and IgG levels, while dasatinib reduced IgM levels. At diagnosis, the proportion of patients with IgA, IgG, and IgM levels below the lower limit of normal (LLN) was 0, 11, and 6% of all CML patients, respectively, whereas at 12 months timepoint the proportions were 6% (p = 0.13), 31% (p = 0.042) and 28% (p = 0.0078). Lower initial Ig levels predisposed to the development of hypogammaglobulinemia during TKI therapy. Decreased Ig levels in imatinibtreated patients were associated with higher percentages of immature BM B cells. The patients, who had low Ig levels during the TKI therapy, had significantly more frequent minor infections during the follow-up compared with the patients with normal Ig values (33% vs. 3%, p = 0.0016). No severe infections were reported, except recurrent upper respiratory tract infections in one imatinib-treated patient, who developed severe hypogammaglobulinemia. Conclusions TKI treatment decreases plasma Ig levels, which should be measured in patients with recurrent infections.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
CML; Tyrosine kinase inhibitor; B cell; Immunoglobulin
National Category
Hematology
Identifiers
urn:nbn:se:liu:diva-139536 (URN)10.1007/s00432-017-2378-6 (DOI)000405312900015 ()28337541 (PubMedID)2-s2.0-85015969804 (Scopus ID)
Note

Funding Agencies|Academy of Finland; Finnish Cancer Societies; Sigrid Juselius Foundation; Finnish Cancer Institute; Signe and Ane Gyllenberg Foundation; Otto A. Malm Foundation; EUTOS project for CML; Pfizer; Novartis; Bristol-Myers Squibb [NordCML006, NordCML007]

Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2018-04-18Bibliographically approved
Skoglund, K., Richter, J., Olsson-Stromberg, U., Bergquist, J., Aluthgedara, W., Ubhayasekera, S. J., . . . Green, H. (2016). In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia. Therapeutic Drug Monitoring, 38(2), 230-238
Open this publication in new window or tab >>In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia
Show others...
2016 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 38, no 2, p. 230-238Article in journal (Refereed) Published
Abstract [en]

Background: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. Methods: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Results: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2016
Keywords
pharmacokinetics; chronic myeloid leukemia; imatinib; CGP74588; CYP3A
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:liu:diva-129678 (URN)10.1097/FTD.0000000000000268 (DOI)000376938000006 ()26693810 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; Medical Research Council of Southeast Sweden; Novartis

Available from: 2016-06-27 Created: 2016-06-23 Last updated: 2018-01-10
Noren, E., Verma, D., Söderkvist, P., Weisselberg, T., Söderman, J., Lotfi, K. & Almer, S. (2016). Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation. Annals of Transplantation, 21, 56-67
Open this publication in new window or tab >>Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation
Show others...
2016 (English)In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 21, p. 56-67Article in journal (Refereed) Published
Abstract [en]

Background: Non-HLA genes may contribute to the prognosis after hematopoietic stem cell transplantation. We investigated associations between single nucleotide polymorphisms in regions of MORC4, CD14, TLR4, NOD2, SLC22A4, SLC22A5, CARD8, NLRP3, and CLDN2 and the outcomes of patients undergoing allogeneic stem cell transplantation. Material/Methods: Single nucleotide polymorphisms in selected regions were determined and analyzed for putative associations with overall mortality and acute graft-versus-host disease. Significant associations were further explored by logistic regression, controlling for additional variables. Results: A significant association was identified between overall mortality among recipients and a nonsynonymous coding variant of MORC4 (rs6622126) in the recipient genetic makeup (P=0.029). Since MORC4 is located on the X-chromosome, the results were also analyzed separately for males and females. The association between overall mortality for recipients and the risk allele (rs6622126; A) was confirmed for males with respect to genetic makeup of recipients (P=0.012), donor genetic makeup (P=0.004), and the combined allele composition of the donor and recipient (P=0.001). A significant association was also identified between overall mortality and the recipient risk allele of CD14 (rs2569190; P=0.031), TLR4 (rs4986790; P=0.043), and NOD2 (carriage of at least 1 mutant allele of rs2066844, rs2066845, or rs2066847; P=0.048). Among the investigated genes, only the CD14 (rs2569190) recipient risk allele was significantly associated with acute graft-versus-host disease (P=0.023). Logistic regression models confirmed these findings, except for NOD2, and also identified a significant contribution by age at stem cell transplantation (MORC4, CD14, TLR4), diagnosis (CD14, TLR4), and prophylaxis (MORC4). Conclusions: Genetic variation in MORC4, CD14, and TLR4 may affect the outcome of allogeneic stem cell transplantation.

Place, publisher, year, edition, pages
Warsaw, Poland: International Scientific Literature, 2016
Keywords
Association Studies; Genetic Predisposition to Disease; Graft vs. Host Disease; Polymorphism, Single Nucleotide; Transplantation, Homologous
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126266 (URN)000371110000001 ()
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-05-03Bibliographically approved
Mosrati, M. A., Willander, K., Jakobsen Falk, I., Hermanson, M., Höglund, M., Stockelberg, D., . . . Söderkvist, P. (2015). Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis. OncoTarget, 6(28), 25109-25120
Open this publication in new window or tab >>Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis
Show others...
2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 28, p. 25109-25120Article in journal (Refereed) Published
Abstract [en]

Telomerase reverse transcriptase gene (TERT) promoter mutations are identified in many malignancies but not in hematological malignancies. Here we analyzed TERT and protection of telomeres 1 gene (POT1) mutations, and four different TERT SNVs in 226 acute myeloid leukemia (AML) patients and 806 healthy individuals in a case referent design, where also overall survival was assessed. A significant association for increased risk of AML was found for TERT SNVs, rs2853669 (OR = 2.45, p = 0.00015) and rs2736100 (OR = 1.5, p = 0.03). The overall survival for patients with CC genotype of rs2853669 was significantly shorter compared to those with TT or TC genotypes (p = 0.036 and 0.029 respectively). The influence of TERT rs2853669 CC on survival was confirmed in multivariable Cox regression analysis as an independent risk biomarker in addition to high risk group, higher age and treatment. No hot spot TERT promoter mutations at -228Cgreater thanT or -250Cgreater thanT or POT1 mutations could be identified in this AML cohort. We show that rs2853669 CC may be a risk factor for the development of AML that may also be used as a prognostic marker to identify high risk normal karyotype -AML (NK-AML) patients, for treatment guidance.

Place, publisher, year, edition, pages
Albany, NY, United States: Impact Journals LLC, 2015
Keywords
TERT; SNV; AML; prognostic markers
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122667 (URN)10.18632/oncotarget.4668 (DOI)000363160100047 ()
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; County Council of Ostergotland; AFA Insurance; FORSS

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2017-12-01Bibliographically approved
Hjorth-Hansen, H., Stenke, L., Söderlund, S., Dreimane, A., Ehrencrona, H., Gedde-Dahl, T., . . . Richter, J. (2015). Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006). European Journal of Haematology, 94(3), 243-250
Open this publication in new window or tab >>Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)
Show others...
2015 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 3, p. 243-250Article in journal (Refereed) Published
Abstract [en]

We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100mg QD or imatinib 400mg QD and report outcome as an intention-to-treat analysis with 36months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3months in 36% vs. 8% (P=0.02), at 12months in 81% vs. 46% (P=0.02) and at 18months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6months onwards, reaching 61% vs. 21% (Pless than0.05) at 36months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
dasatinib; imatinib; randomized controlled trial; deep response; toxicity
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-116957 (URN)10.1111/ejh.12423 (DOI)000350357900008 ()25082346 (PubMedID)
Note

Funding Agencies|Bristol-Myers Squibb

Available from: 2015-04-10 Created: 2015-04-10 Last updated: 2017-12-04
Frödin, U., Lotfi, K., Fomichov, V., Juliusson, G. & Börjeson, S. (2015). Frequent and long-term follow-up of health-related quality of life following allogeneic haematopoietic stem cell transplantation. European Journal of Cancer Care, 24(6), 898-910
Open this publication in new window or tab >>Frequent and long-term follow-up of health-related quality of life following allogeneic haematopoietic stem cell transplantation
Show others...
2015 (English)In: European Journal of Cancer Care, ISSN 0961-5423, E-ISSN 1365-2354, Vol. 24, no 6, p. 898-910Article in journal (Refereed) Published
Abstract [en]

Health-related quality of life (HRQL) was evaluated in 94 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) after myeloablative (MAC, n=18) or reduced intensity conditioning (RIC, n=76). HRQL was assessed with the EORTC QLQ C-30 during the inpatient period as well as during the following 3years, i.e. at baseline and 12 times thereafter. Functional status and global quality of life decreased from baseline to weeks 2 and 3, especially role and social functions. Symptoms increased significantly during the first 3weeks, particularly appetite loss, nausea and vomiting, diarrhoea and fatigue. It took at least 1year for HRQL to return to the baseline level. The only function that improved significantly 3years after HSCT was role function. Patients treated with MAC experienced significantly worse HRQL at baseline than patients treated with RIC, as well as more pain, sleep disturbance and appetite loss in weeks 3 and 4. Patients with extensive chronic graft-versus-host disease experienced reduced HRQL. These results provide a clinically useful overview of patients HRQL during and after HSCT and indicate when they require increased support. The results demonstrate the importance of close follow-ups during the first year after HSCT to improve preventive or supportive interventions.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keywords
quality of life; symptom; stem cell transplantation
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:liu:diva-122649 (URN)10.1111/ecc.12350 (DOI)000363466200014 ()26156141 (PubMedID)
Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2017-12-01Bibliographically approved
Jangamreddy, J. R., Jain, M. V., Hallbeck, A.-L., Roberg, K., Lotfi, K. & Los, M. J. (2015). Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death. OncoTarget, 6(12), 10134-10145
Open this publication in new window or tab >>Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death
Show others...
2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 12, p. 10134-10145Article in journal (Refereed) Published
Abstract [en]

Salinomycin has been used as treatment for malignant tumors in a small number of humans, causing far less side effects than standard chemotherapy. Several studies show that Salinomycin targets cancer-initiating cells (cancer stem cells, or CSC) resistant to conventional therapies. Numerous studies show that Salinomycin not only reduces tumor volume, but also decreases tumor recurrence when used as an adjuvant to standard treatments. In this study we show that starvation triggered different stress responses in cancer cells and primary normal cells, which further improved the preferential targeting of cancer cells by Salinomycin. Our in vitro studies further demonstrate that the combined use of 2-Fluoro 2-deoxy D-glucose, or 2-deoxy D-glucose with Salinomycin is lethal in cancer cells while the use of Oxamate does not improve cell death-inducing properties of Salinomycin. Furthermore, we show that treatment of cancer cells with Salinomycin under starvation conditions not only increases the apoptotic caspase activity, but also diminishes the protective autophagy normally triggered by the treatment with Salinomycin alone. Thus, this study underlines the potential use of Salinomycin as a cancer treatment, possibly in combination with short-term starvation or starvation-mimicking pharmacologic intervention.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2015
Keywords
Glucose starvation, 2DG, 2FDG, Normoxia and Hypoxia, Differential Stress Response, autophagy, Akt, Tricirabine, Salinomycin
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-113707 (URN)000358874600039 ()
Available from: 2015-01-29 Created: 2015-01-29 Last updated: 2018-01-11Bibliographically approved
Organisations

Search in DiVA

Show all publications