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Article: Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery.

Adekeye, Adenike O / Needham, David / Rahman, Ruman

2023 Volume 15, Issue 2

Abstract: Metabolic reprogramming, through increased uptake of cholesterol in the form of low-density lipoproteins (LDL), is one way by which cancer cells, including high grade gliomas (HGG), maintain their rapid growth. In this study, we determined LDL receptor ( ... ...

Abstract	Metabolic reprogramming, through increased uptake of cholesterol in the form of low-density lipoproteins (LDL), is one way by which cancer cells, including high grade gliomas (HGG), maintain their rapid growth. In this study, we determined LDL receptor (LDLR) expression in HGGs using immunohistochemistry on tissue microarrays from intra- and inter tumour regions of 36 adult and 133 paediatric patients to confirm LDLR as a therapeutic target. Additionally, we analysed expression levels in three representative cell line models to confirm their future utility to test LDLR-targeted nanoparticle uptake, retention, and cytotoxicity. Our data show widespread LDLR expression in adult and paediatric cohorts, but with significant intra-tumour variation observed between the core and either rim or invasive regions of adult HGG. Expression was independent of paediatric tumour grade or identified clinicopathological factors. LDLR-expressing tumour cells localized preferentially within perivascular niches, also with significant adult intra-tumour variation. We demonstrated variable levels of LDLR expression in all cell lines, confirming their suitability as models to test LDLR-targeted nanotherapy delivery. Overall, our study reveals the LDLR pathway as a ubiquitous metabolic vulnerability in high grade gliomas across all ages, amenable to future consideration of LDL-mediated nanoparticle/drug delivery to potentially circumvent tumour heterogeneity.
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15020599
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Biomaterial-based local drug delivery to brain tumors.

Rahman, Ruman

Therapeutic delivery

2014 Volume 5, Issue 12, Page(s) 1243–1245

MeSH term(s)	Biocompatible Materials ; Brain Neoplasms/drug therapy ; Delayed-Action Preparations ; Drug Delivery Systems/methods ; Glioblastoma/drug therapy ; Humans ; Polymers/chemistry ; Technology, Pharmaceutical/methods
Chemical Substances	Biocompatible Materials ; Delayed-Action Preparations ; Polymers
Language	English
Publishing date	2014-12
Publishing country	England
Document type	Editorial
ISSN	2041-5990
ISSN	2041-5990
DOI	10.4155/tde.14.83
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Article ; Online: Transcription Profile and Pathway Analysis of the Endocannabinoid Receptor Inverse Agonist AM630 in the Core and Infiltrative Boundary of Human Glioblastoma Cells

Gareth Williams / David Chambers / Ruman Rahman / Francisco Molina-Holgado

Molecules, Vol 27, Iss 2049, p

2022 Volume 2049

Abstract: Background: We have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumour cell proliferation. To uncover the mechanism behind the anti- ... ...

Abstract	Background: We have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumour cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour core cells (U87) and the invasive margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease. Results: The core and invasive margin cells exhibited markedly different gene expression profiles and only the core cells had high expression of a potential AM630 target, the CB1 receptor. Both cell types had moderate expression of the HTR2B serotonin receptor, a reported AM630 target. We found that the AM630 driven transcriptional response was substantially higher in the central cells than in the invasive margin cells, with the former driving the up regulation of immune response and the down regulation of cell cycle and metastatic pathways and correlating with transcriptional responses driven by established anti-neoplastics as well as serotonin receptor antagonists. Conclusion: Our results highlight the different gene sets involved in the core and invasive margin cell lines derived from GBM and an associated marked difference in responsiveness to AM630. Our findings identify AM630 as an anti-neoplastic drug in the context of the core cells, showing a high correlation with the activity of known antiproliferative drugs. However, we reveal a key set of similarities between the two cell lines that may inform therapeutic intervention.
Keywords	brain cancer ; glioblastoma ; CB2 cannabinoid receptor ; gene expression ; Organic chemistry ; QD241-441
Subject code	570
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Transcription Profile and Pathway Analysis of the Endocannabinoid Receptor Inverse Agonist AM630 in the Core and Infiltrative Boundary of Human Glioblastoma Cells.

Williams, Gareth / Chambers, David / Rahman, Ruman / Molina-Holgado, Francisco

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 7

Abstract	Background: We have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumour cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour core cells (U87) and the invasive margin cells (GIN-8), the latter representing a better proxy of post-surgical residual disease. Results: The core and invasive margin cells exhibited markedly different gene expression profiles and only the core cells had high expression of a potential AM630 target, the CB1 receptor. Both cell types had moderate expression of the HTR2B serotonin receptor, a reported AM630 target. We found that the AM630 driven transcriptional response was substantially higher in the central cells than in the invasive margin cells, with the former driving the up regulation of immune response and the down regulation of cell cycle and metastatic pathways and correlating with transcriptional responses driven by established anti-neoplastics as well as serotonin receptor antagonists. Conclusion: Our results highlight the different gene sets involved in the core and invasive margin cell lines derived from GBM and an associated marked difference in responsiveness to AM630. Our findings identify AM630 as an anti-neoplastic drug in the context of the core cells, showing a high correlation with the activity of known antiproliferative drugs. However, we reveal a key set of similarities between the two cell lines that may inform therapeutic intervention.
MeSH term(s)	Down-Regulation ; Glioblastoma/drug therapy ; Humans ; Indoles/pharmacology ; Receptor, Cannabinoid, CB1/agonists
Chemical Substances	Indoles ; Receptor, Cannabinoid, CB1 ; iodopravadoline (U1LNJ6NBKA)
Language	English
Publishing date	2022-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27072049
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Article ; Online: High burden of hypovitaminosis D among the children and adolescents in South Asia: a systematic review and meta-analysis.

Siddiqee, Mahbubul H / Bhattacharjee, Badhan / Siddiqi, Umme Ruman / Rahman, Mohammad Meshbahur

Journal of health, population, and nutrition

2022 Volume 41, Issue 1, Page(s) 10

Abstract: Background: Vitamin D is vital for the growth and development of children. While deficiency and/or insufficiency of vitamin D among South Asian children are frequently reported in the literature, the lack of a meta-analysis has left its true extent ... ...

Abstract	Background: Vitamin D is vital for the growth and development of children. While deficiency and/or insufficiency of vitamin D among South Asian children are frequently reported in the literature, the lack of a meta-analysis has left its true extent poorly characterized. In this study, we aimed to conduct a systematic review and perform meta-analyses of the prevalence of hypovitaminosis D among the children of the South Asian countries. Methods: Two major electronic search engines (PubMed and Scopus) and one database (Google scholar) were used; original studies, conducted among South Asian children and adolescents and published between 1 January 2001 and 31 December 2019. A random-effect meta-analysis was also performed to calculate the pooled prevalence of hypovitaminosis D followed by subgroup analyses for countries and age groups. Results: After applying inclusion and exclusion criteria, a total of 41 studies with a total population size of 18,233 were finally selected. The overall prevalence of hypovitaminosis D was 61% [95% CI: 46% to 71%] with highly significant heterogeneity (I Conclusion: This study generates quantitative evidence and specific extent of hypovitaminosis D in the South Asian countries as a public health concern. Being the first systematic review for this region, results from this study will create awareness and will facilitate adopting mitigation strategies by the policymakers and the governments to address this problem.
MeSH term(s)	Adolescent ; Child, Preschool ; Humans ; India/epidemiology ; Infant, Newborn ; Prevalence ; Sri Lanka/epidemiology ; Vitamin D ; Vitamin D Deficiency/epidemiology
Chemical Substances	Vitamin D (1406-16-2)
Language	English
Publishing date	2022-03-17
Publishing country	Bangladesh
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review
ZDB-ID	2025045-9
ISSN	2072-1315 ; 1606-0997
ISSN (online)	2072-1315
ISSN	1606-0997
DOI	10.1186/s41043-022-00287-w
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Article ; Online: Rationally designed drug delivery systems for the local treatment of resected glioblastoma.

Bastiancich, Chiara / Malfanti, Alessio / Préat, Véronique / Rahman, Ruman

Advanced drug delivery reviews

2021 Volume 177, Page(s) 113951

Abstract: Glioblastoma (GBM) is a particularly aggressive brain cancer associated with high recurrence and poor prognosis. The standard of care, surgical resection followed by concomitant radio- and chemotherapy, leads to low survival rates. The local delivery of ... ...

Abstract	Glioblastoma (GBM) is a particularly aggressive brain cancer associated with high recurrence and poor prognosis. The standard of care, surgical resection followed by concomitant radio- and chemotherapy, leads to low survival rates. The local delivery of active agents within the tumor resection cavity has emerged as an attractive means to initiate oncological treatment immediately post-surgery. This complementary approach bypasses the blood-brain barrier, increases the local concentration at the tumor site while reducing or avoiding systemic side effects. This review will provide a global overview on the local treatment for GBM with an emphasis on the lessons learned from past clinical trials. The main parameters to be considered to rationally design fit-of-purpose biomaterials and develop drug delivery systems for local administration in the GBM resection cavity to prevent the tumor recurrence will be described. The intracavitary local treatment of GBM should i) use materials that facilitate translation to the clinic; ii) be characterized by easy GMP effective scaling up and easy-handling application by the neurosurgeons; iii) be adaptable to fill the tumor-resected niche, mold to the resection cavity or adhere to the exposed brain parenchyma; iv) be biocompatible and possess mechanical properties compatible with the brain; v) deliver a therapeutic dose of rationally-designed or repurposed drug compound(s) into the GBM infiltrative margin. Proof of concept with high translational potential will be provided. Finally, future perspectives to facilitate the clinical translation of the local perisurgical treatment of GBM will be discussed.
MeSH term(s)	Animals ; Biocompatible Materials/administration & dosage ; Brain Neoplasms/drug therapy ; Brain Neoplasms/surgery ; Drug Delivery Systems ; Glioblastoma/drug therapy ; Glioblastoma/surgery ; Humans ; Translational Science, Biomedical
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2021-08-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2021.113951
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Article ; Online: Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Cavanagh, Robert J / Monteiro, Patrícia F / Moloney, Cara / Travanut, Alessandra / Mehradnia, Fatemeh / Taresco, Vincenzo / Rahman, Ruman / Martin, Stewart G / Grabowska, Anna M / Ashford, Marianne B / Alexander, Cameron

Biomaterials science

2024 Volume 12, Issue 7, Page(s) 1822–1840

Abstract: Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we ... ...

Abstract	Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed
MeSH term(s)	Humans ; Triple Negative Breast Neoplasms/metabolism ; Reactive Oxygen Species ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Drug Combinations ; Nanoparticles ; Cell Line, Tumor ; Phthalazines ; Piperazines
Chemical Substances	olaparib (WOH1JD9AR8) ; Reactive Oxygen Species ; Antineoplastic Agents ; Doxorubicin (80168379AG) ; Poly(ADP-ribose) Polymerase Inhibitors ; Drug Combinations ; Phthalazines ; Piperazines
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d3bm01931d
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Article ; Online: Investigating histidinylated highly branched poly(lysine) for siRNA delivery.

Alazzo, Ali / Gumus, Nurcan / Gurnani, Pratik / Stolnik, Snjezana / Rahman, Ruman / Spriggs, Keith / Alexander, Cameron

Journal of materials chemistry. B

2022 Volume 10, Issue 2, Page(s) 236–246

Abstract: The temporary silencing of disease-associated genes utilising short interfering RNA (siRNA) is a potent and selective route for addressing a wide range of life limiting disorders. However, the few clinically approved siRNA therapies rely on lipid based ... ...

Abstract	The temporary silencing of disease-associated genes utilising short interfering RNA (siRNA) is a potent and selective route for addressing a wide range of life limiting disorders. However, the few clinically approved siRNA therapies rely on lipid based formulations, which although potent, provide limited chemical space to tune the stability, efficacy and tissue selectivity. In this study, we investigated the role of molar mass and histidinylation for poly(lysine) based non-viral vectors, synthesised through a fully aqueous thermal condensation polymerisation. Formulation and
MeSH term(s)	Cell Line, Tumor ; Cell Membrane/drug effects ; Drug Carriers/chemistry ; Gene Knockdown Techniques ; Gene Silencing/drug effects ; Histidine/analogs & derivatives ; Humans ; Molecular Structure ; Molecular Weight ; Polylysine/chemistry ; RNA, Small Interfering/genetics ; RNA, Small Interfering/pharmacology
Chemical Substances	Drug Carriers ; RNA, Small Interfering ; Polylysine (25104-18-1) ; Histidine (4QD397987E)
Language	English
Publishing date	2022-01-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d1tb01793d
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Article ; Online: High prevalence of vitamin D insufficiency among South Asian pregnant women: a systematic review and meta-analysis.

Siddiqee, Mahbubul Hasan / Bhattacharjee, Badhan / Siddiqi, Umme Ruman / Rahman, Mohammad Meshbhaur

The British journal of nutrition

2021 Volume 128, Issue 6, Page(s) 1118–1129

Abstract: Insufficiency of vitamin D, during pregnancy, is a common cause of various pregnancy-related complications. Despite such insufficiency being frequently reported among South Asian pregnant women, the absence of systematic review and meta-analysis renders ... ...

Abstract	Insufficiency of vitamin D, during pregnancy, is a common cause of various pregnancy-related complications. Despite such insufficiency being frequently reported among South Asian pregnant women, the absence of systematic review and meta-analysis renders the true extent of this problem being poorly characterised. In this systematic review, three main databases (PubMed, Scopus and Google Scholar) were searched for original studies. We included original studies published between 1January 2001 to 31 December 2019, conducted on pregnant women who lived in South Asian countries and reported the prevalence of vitamin D insufficiency among the study participants. Twenty studies with a total of 7804 participants from four South Asian countries finally met our selection criteria. Overall pooled prevalence of insufficiency was 65 % (95 % CI: 51 %, 78 %) with a significant heterogeneity (I
MeSH term(s)	Humans ; Female ; Pregnancy ; Vitamin D ; Pregnant Women ; Prevalence ; South Asian People ; Vitamins ; Pregnancy Complications/epidemiology ; Vitamin D Deficiency/epidemiology
Chemical Substances	Vitamin D (1406-16-2) ; Vitamins
Language	English
Publishing date	2021-11-02
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114521004360
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Article: Using Light for Therapy of Glioblastoma Multiforme (GBM).

Vasilev, Alex / Sofi, Roba / Rahman, Ruman / Smith, Stuart J / Teschemacher, Anja G / Kasparov, Sergey

Brain sciences

2020 Volume 10, Issue 2

Abstract: ...

Abstract	:
Language	English
Publishing date	2020-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci10020075
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