Imperial College London

Emeritus ProfessorMustafaDjamgoz

Faculty of Natural SciencesDepartment of Life Sciences

Emeritus Professor in Cancer Biology
 
 
 
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Contact

 

+44 (0)20 7594 5370m.djamgoz

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

341 results found

Djamgoz MBA, 2024, Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels., Br J Cancer

BACKGROUND: Multi-faceted evidence from a range of cancers suggests strongly that de novo expression of voltage-gated sodium channels (VGSCs) plays a significant role in driving cancer cell invasiveness. Under hypoxic conditions, common to growing tumours, VGSCs develop a persistent current (INaP) which can be blocked selectively by ranolazine. METHODS: Several different carcinomas were examined. We used data from a range of experimental approaches relating to cellular invasiveness and metastasis. These were supplemented by survival data mined from cancer patients. RESULTS: In vitro, ranolazine inhibited invasiveness of cancer cells especially under hypoxia. In vivo, ranolazine suppressed the metastatic abilities of breast and prostate cancers and melanoma. These data were supported by a major retrospective epidemiological study on breast, colon and prostate cancer patients. This showed that risk of dying from cancer was reduced by ca.60% among those taking ranolazine, even if this started 4 years after the diagnosis. Ranolazine was also shown to reduce the adverse effects of chemotherapy on heart and brain. Furthermore, its anti-cancer effectiveness could be boosted by co-administration with other drugs. CONCLUSIONS: Ranolazine, alone or in combination with appropriate therapies, could be reformulated as a safe anti-metastatic drug offering many potential advantages over current systemic treatment modalities.

Journal article

Rizaner N, Fraser SP, Gul IB, Purut E, Djamgoz MBA, Altun Set al., 2024, Lidocaine Inhibits Rat Prostate Cancer Cell Invasiveness and Voltage-Gated Sodium Channel Expression in Plasma Membrane., J Membr Biol

There is increasing evidence, mostly from breast cancer, that use of local anaesthetics during surgery can inhibit disease recurrence by suppressing the motility of the cancer cells dependent on inherent voltage-gated sodium channels (VGSCs). Here, the possibility that lidocaine could affect cellular behaviours associated with metastasis was tested using the Dunning cell model of rat prostate cancer. Mostly, the strongly metastatic (VGSC-expressing) Mat-LyLu cells were used under both normoxic and hypoxic conditions. The weakly metastatic AT-2 cells served for comparison in some experiments. Lidocaine (1-500 μM) had no effect on cell viability or growth but suppressed Matrigel invasion dose dependently in both normoxia and hypoxia. Used as a control, tetrodotoxin produced similar effects. Exposure to hypoxia increased Nav1.7 mRNA expression but VGSCα protein level in plasma membrane was reduced. Lidocaine under both normoxia and hypoxia had no effect on Nav1.7 mRNA expression. VGSCα protein expression was suppressed by lidocaine under normoxia but no effect was seen in hypoxia. It is concluded that lidocaine can suppress prostate cancer invasiveness without effecting cellular growth or viability. Extended to the clinic, the results would suggest that use of lidocaine, and possibly other local anaesthetics, during surgery can suppress any tendency for post-operative progression of prostate cancer.

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Djamgoz MBA, 2023, An Interview with Sally Adee, the Author of the Book "We Are Electric", BIOELECTRICITY, Vol: 5, Pages: 216-219, ISSN: 2576-3105

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Foust A, 2023, Voltage-sensitive optical probes for measuring cell membrane potentials: An update and applications to ‘non-excitable’ cells, Bioelectricity, ISSN: 2576-3105

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Folcher A, Gordienko D, Iamshanova O, Bokhobza A, Shapovalov G, Kannancheri-Puthooru D, Mariot P, Allart L, Desruelles E, Spriet C, Diez R, Oullier T, Marionneau-Lambot S, Brisson L, Geraci S, Impheng H, Lehen'kyi V, Haustrate A, Mihalache A, Gosset P, Chadet S, Retif S, Laube M, Sobilo J, Lerondel S, Villari G, Serini G, Pla AF, Roger S, Fromont-Hankard G, Djamgoz M, Clezardin P, Monteil A, Prevarskaya Net al., 2023, NALCN-mediated sodium influx confers metastatic prostate cancer cell invasiveness, EMBO JOURNAL, Vol: 42, ISSN: 0261-4189

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Djamgoz MBA, Levin M, 2023, Bioelectricity: A Multifaceted Discipline, and a Multifaceted Issue!, BIOELECTRICITY, Vol: 5, Pages: 75-75, ISSN: 2576-3105

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Djamgoz MBA, Levin M, 2022, Another Leap Forward for <i>Bioelectricity</i>, BIOELECTRICITY, Vol: 4, Pages: 189-189, ISSN: 2576-3105

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Quicke P, Sun Y, Beykou M, Arias-Garcia M, Bakal C, Djamgoz M, Acker C, Foust Aet al., 2022, Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells, Communications Biology, Vol: 5, ISSN: 2399-3642

Cancer cells feature a resting membrane potential (Vm) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to ‘excitable’ tissues, relatively little is known about cancer cell Vm dynamics. Here high-throughput, cellular-resolution Vm imaging reveals that Vm fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells. We characterize Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy” to “blinking/waving“. The Vm of MDA-MB-231 cells exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, and by calcium-activated potassium channel inhibitors apamin and iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generate Vm fluctuations may be a property of hybrid epithelial-mesenchymal cells or those originated from luminal progenitors.

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Djamgoz MBA, Levin M, 2022, <i>Bioelectricity</i>: An Update, BIOELECTRICITY, Vol: 4, Pages: 135-135, ISSN: 2576-3105

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Yerlikaya S, Djamgoz MBA, 2022, Oleamide, a Primary Fatty Acid Amide: Effects on Ion Channels and Cancer, BIOELECTRICITY, Vol: 4, Pages: 136-144, ISSN: 2576-3105

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Djamgoz MBA, 2022, Bioelectricity Industry News, BIOELECTRICITY, Vol: 4, Pages: 186-188, ISSN: 2576-3105

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Qiu S, Fraser SP, Pires W, Djamgoz MBAet al., 2022, Anti-invasive effects of minoxidil on human breast cancer cells: combination with ranolazine, CLINICAL & EXPERIMENTAL METASTASIS, Vol: 39, Pages: 679-689, ISSN: 0262-0898

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Djamgoz MBA, 2022, Rosalind Franklin Society: Mary Ann Liebert Award in Science (2021), BIOELECTRICITY, Vol: 4, Pages: 133-133, ISSN: 2576-3105

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Djamgoz MBA, 2022, Comments on: Antiepileptic drugs and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer, INTERNATIONAL JOURNAL OF CANCER, Vol: 150, Pages: 1212-1213, ISSN: 0020-7136

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Djamgoz MBA, Jentzsch V, 2022, Integrative management of pancreatic cancer (PDAC): emerging complementary agents and modalities, Nutrition and Cancer: an international journal, Vol: 74, Pages: 1139-1162, ISSN: 0163-5581

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. The standard first-line treatment for PDAC is gemcitabine chemotherapy which, unfortunately, offers only limited chance of a lasting cure. This review further evaluates the hypothesis that the effectiveness of gemcitabine can be improved by combining it with evidence-based complementary measures. Previously, supported by clinical trial data, we suggested that a number of dietary factors and nutraceuticals can be integrated with gemcitabine therapy. Here, we evaluate a further 10 agents for which no clinical trials have (yet) been carried out but there are promising data from in vivo and/or in vitro studies including experiments involving combined treatments with gemcitabine. Two groups of complementary agents are considered: Dietary factors (resveratrol, epigallocatechin gallate, vitamin B9, capsaicin, quercetin and sulforaphane) and nutraceutical agents (artemisinin, garcinol, thymoquinone and emodin). In addition, we identified seven promising agents for which there is currently only basic (mostly in vitro) data. Finally, as a special case of combination therapy, we highlighted synergistic drug combinations involving gemcitabine with “repurposed” aspirin or metformin. We conclude overall that integrated management of PDAC currently is likely to produce the best outcome for patients and for this a wide range of complementary measures is available.

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Levin M, Djamgoz MBA, 2022, Bioelectricity: From Endogenous Mechanisms to Opportunities in Synthetic Bioengineering, BIOELECTRICITY, Vol: 4, Pages: 1-2, ISSN: 2576-3105

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Fraser SP, Onkal R, Theys M, Bosmans F, Djamgoz MBAet al., 2022, Neonatal Na<sub>V</sub>1.5 channels: pharmacological distinctiveness of a cancer-related voltage-gated sodium channel splice variant, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 179, Pages: 473-486, ISSN: 0007-1188

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Djamgoz MBA, 2022, Ion Transporting Proteins and Cancer: Progress and Perspectives, TARGETS OF CANCER DIAGNOSIS AND TREATMENT, Vol: 183, Pages: 251-277, ISSN: 0303-4240

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Djamgoz MBA, 2021, 3rd International Meeting on Cancer and Ion Channels September 16-18, 2021; Istanbul Medipol University, Kavacik, Istanbul, Turkey, BIOELECTRICITY, Vol: 3, Pages: 292-293, ISSN: 2576-3105

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Djamgoz MBA, Pchelintseva E, 2021, Mechanosensitive Ion Channels and Stem Cell Differentiation, BIOELECTRICITY, Vol: 3, Pages: 249-254, ISSN: 2576-3105

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Djamgoz MBA, Levin M, 2021, Bioelectricity Is the Bridge Where Cancer Meets Neuroscience, BIOELECTRICITY, Vol: 3, Pages: 159-160, ISSN: 2576-3105

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Fraser SP, Tesi A, Bonito B, Hui MKM, Arcangeli A, Djamgoz MBAet al., 2021, Potassium Channel Blockage and Invasiveness of Strongly Metastatic Prostate and Breast Cancer Cells, BIOELECTRICITY, Vol: 3, Pages: 215-220, ISSN: 2576-3105

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Lastraioli E, Fraser SP, Guzel RM, Iorio J, Bencini L, Scarpi E, Messerini L, Villanacci V, Cerino G, Ghezzi N, Perrone G, Djamgoz MBA, Arcangeli Aet al., 2021, Neonatal Nav1.5 protein expression in human colorectal cancer: immunohistochemical characterization and clinical evaluation, Cancers, Vol: 13, Pages: 1-14, ISSN: 2072-6694

Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker (‘companion diagnostic’) useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.

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Phillips JA, Hutchings C, Djamgoz MBA, 2021, Clinical Potential of Nerve Input to Tumors: A Bioelectricity Perspective, BIOELECTRICITY, Vol: 3, Pages: 14-26, ISSN: 2576-3105

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Djamgoz MBA, Levin M, 2021, Call for Special Issue Papers: The Bioelectricity of Connective TissueCells and their Environments, BIOELECTRICITY, Vol: 3, Pages: 2-2, ISSN: 2576-3105

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Firmenich L, Djamgoz MBA, 2020, Society of General Physiologists Symposium on "Ion Channels and Transporters in Immunity, Inflammation and Antitumor Immunity" (held online on September 11, 2020), BIOELECTRICITY, Vol: 2, Pages: 418-423, ISSN: 2576-3105

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Hutchings C, Phillips JA, Djamgoz MBA, 2020, Nerve input to tumours: Pathophysiological consequences of a dynamic relationship, BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, Vol: 1874, ISSN: 0304-419X

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Jentzsch V, Davis JAA, Djamgoz MBA, 2020, Pancreatic Cancer (PDAC): introduction of evidence-based complementary measures into integrative clinical management, Cancers, Vol: 12, Pages: 1-62, ISSN: 2072-6694

The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating ‘western’ clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main ‘hallmarks of cancer’. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chem

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Rizaner N, Uzun S, Fraser SP, Djamgoz MBA, Altun Set al., 2020, Riluzole: Anti-invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions, BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, Vol: 127, Pages: 254-264, ISSN: 1742-7835

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