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Article ; Online: Efficacy and safety profiles of programmed cell death-1/programmed cell death ligand-1 inhibitors in the treatment of triple-negative breast cancer

Gilbert Lazarus / Jessica Audrey / Anthony William Brian Iskandar

Oncology Reviews, Vol 13, Iss

a comprehensive systematic review

2019 Volume 2

Abstract: Triple-negative breast cancer (TNBC) is associated with worse prognosis, with limited treatment regiments available and higher mortality rate. Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) ...

Abstract	Triple-negative breast cancer (TNBC) is associated with worse prognosis, with limited treatment regiments available and higher mortality rate. Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) showed great potentials in treating malignancies and may serve as potential therapies for TNBC. This systematic review aims to evaluate the efficacy and safety profiles of PD-1/PD-L1 inhibitors in the treatment of TNBC. Literature search was performed via PubMed, EBSCOhost, Scopus, and CENTRAL databases, selecting studies which evaluated the use of anti-PD-1/PD-L1 for TNBC from inception until February 2019. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). Overall, 7 studies evaluating outcomes of 1395 patients with TNBC were included in this systematic review. Anti-PD-1/PD-L1 showed significant antitumor effect, proven by their promising response (objective response rate (ORR), 18.5-39.4%) and survival rates (median overall survival (OS), 9.2-21.3 months). Moreover, anti-PD-1/PD-L1 yielded better outcomes when given as first-line therapy, and overexpression of PD-L1 in tumors showed better therapeutic effects. On the other hands, safety profiles were similar across agents and generally acceptable, with grade ≥3 treatment-related adverse effects (AEs) ranging from 9.5% to 15.6% and no new AEs were experienced by TNBC patients. Most grade ≥3 AEs are immune-mediated, which are manifested as neutropenia, fatigue, peripheral neuropathy, and anemia. PD-1/PD-L1 inhibitors showed promising efficacy and tolerable AEs, and thus may benefit TNBC patients. Further studies of randomized controlled trials with larger populations are needed to better confirm the potential of these agents.
Keywords	Checkpoint inhibitor ; programmed cell death-1 ; programmed cell death-ligand 1 ; triple-negative breast cancer ; Other systems of medicine ; RZ201-999 ; Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	PAGEPress Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Contributory Factors Influencing Interdisciplinary Pediatric Weight Management Program Attendance for Racially Minoritized Youth.

Anastasiadis, William A / Bazier, Ashley / Gilbert, Elaine / Schwartzkopf, Katherine / Benson, Kari / Perkins, Anthony J / Naramore, Sara K

Journal of clinical psychology in medical settings

2022 Volume 30, Issue 2, Page(s) 297–309

Abstract: Childhood obesity is a complex medical condition associated with biopsychosocial complications that requires a multifaceted treatment approach. Historically weight management treatment has been challenging to access for racially minoritized youth. This ... ...

Abstract	Childhood obesity is a complex medical condition associated with biopsychosocial complications that requires a multifaceted treatment approach. Historically weight management treatment has been challenging to access for racially minoritized youth. This study evaluated factors influencing treatment attendance for racially minoritized youth in a pediatric weight management program between 2018 and 2021. Medical information from 228 participants was collected, including demographics, insurance type, use of telehealth visits, measures of health-related quality of life (HRQOL), distance from the weight management program, and medical history. Although participants entering the weight management program came from across the state, racially minoritized participants from the Indianapolis area were more likely to attend the program. Racially minoritized participants farther from the program were comparatively underrepresented. Relative to families from majority backgrounds, racially minoritized families had the highest public health insurance rates. Specific physical and mental health comorbidities may further increase risk. Results have important implications for pediatric weight management programs to improve access and treatment opportunities for racially minoritized and underserved populations.
MeSH term(s)	Humans ; Child ; Adolescent ; Pediatric Obesity/therapy ; Weight Reduction Programs ; Quality of Life/psychology
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	1235893-9
ISSN	1573-3572 ; 1068-9583
ISSN (online)	1573-3572
ISSN	1068-9583
DOI	10.1007/s10880-022-09899-0
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Article: Efficacy and safety profiles of programmed cell death-1/programmed cell death ligand-1 inhibitors in the treatment of triple-negative breast cancer: A comprehensive systematic review.

Lazarus, Gilbert / Audrey, Jessica / Iskandar, Anthony William Brian

Oncology reviews

2019 Volume 13, Issue 2, Page(s) 425

Abstract	Triple-negative breast cancer (TNBC) is associated with worse prognosis, with limited treatment regiments available and higher mortality rate. Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) showed great potentials in treating malignancies and may serve as potential therapies for TNBC. This systematic review aims to evaluate the efficacy and safety profiles of PD-1/PD-L1 inhibitors in the treatment of TNBC. Literature search was performed via PubMed, EBSCOhost, Scopus, and CENTRAL databases, selecting studies which evaluated the use of anti-PD-1/PDL1 for TNBC from inception until February 2019. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). Overall, 7 studies evaluating outcomes of 1395 patients with TNBC were included in this systematic review. Anti-PD-1/PD-L1 showed significant antitumor effect, proven by their promising response (objective response rate (ORR), 18.5-39.4%) and survival rates (median overall survival (OS), 9.2-21.3 months). Moreover, anti- PD-1/PD-L1 yielded better outcomes when given as first-line therapy, and overexpression of PD-L1 in tumors showed better therapeutic effects. On the other hands, safety profiles were similar across agents and generally acceptable, with grade ≥3 treatment- related adverse effects (AEs) ranging from 9.5% to 15.6% and no new AEs were experienced by TNBC patients. Most grade ≥3 AEs are immune-mediated, which are manifested as neutropenia, fatigue, peripheral neuropathy, and anemia. PD-1/PD-L1 inhibitors showed promising efficacy and tolerable AEs, and thus may benefit TNBC patients. Further studies of randomized controlled trials with larger populations are needed to better confirm the potential of these agents.
Language	English
Publishing date	2019-10-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2390302-8
ISSN	1970-5565 ; 1970-5565 ; 1970-5557
ISSN (online)	1970-5565
ISSN	1970-5565 ; 1970-5557
DOI	10.4081/oncol.2019.425
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Article: Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology.

Hills, Rory A / Kit Tan, Tiong / Cohen, Alexander A / Keeffe, Jennifer R / Keeble, Anthony H / Gnanapragasam, Priyanthi N P / Storm, Kaya N / Hill, Michelle L / Liu, Sai / Gilbert-Jaramillo, Javier / Afzal, Madeeha / Napier, Amy / James, William S / Bjorkman, Pamela J / Townsend, Alain R / Howarth, Mark

bioRxiv : the preprint server for biology

2023

Abstract: Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a ... ...

Abstract	Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection.
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.24.529520
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Article ; Online: The level of oncogenic Ras determines the malignant transformation of Lkb1 mutant tissue in vivo.

Rackley, Briana / Seong, Chang-Soo / Kiely, Evan / Parker, Rebecca E / Rupji, Manali / Dwivedi, Bhakti / Heddleston, John M / Giang, William / Anthony, Neil / Chew, Teng-Leong / Gilbert-Ross, Melissa

Communications biology

2021 Volume 4, Issue 1, Page(s) 142

Abstract: The genetic and metabolic heterogeneity of RAS-driven cancers has confounded therapeutic strategies in the clinic. To address this, rapid and genetically tractable animal models are needed that recapitulate the heterogeneity of RAS-driven cancers in vivo. ...

Abstract	The genetic and metabolic heterogeneity of RAS-driven cancers has confounded therapeutic strategies in the clinic. To address this, rapid and genetically tractable animal models are needed that recapitulate the heterogeneity of RAS-driven cancers in vivo. Here, we generate a Drosophila melanogaster model of Ras/Lkb1 mutant carcinoma. We show that low-level expression of oncogenic Ras (Ras
MeSH term(s)	AMP-Activated Protein Kinase Kinases ; AMP-Activated Protein Kinases/metabolism ; Adenocarcinoma of Lung/enzymology ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/mortality ; Animals ; Animals, Genetically Modified ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Death ; Cell Movement ; Databases, Genetic ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/embryology ; Drosophila melanogaster/enzymology ; Drosophila melanogaster/genetics ; Enzyme Activation ; Genes, ras ; Genetic Predisposition to Disease ; Humans ; Larva/enzymology ; Larva/genetics ; Lung Neoplasms/enzymology ; Lung Neoplasms/genetics ; Lung Neoplasms/mortality ; Mutation ; Neoplasm Invasiveness ; Neoplasms, Experimental/enzymology ; Neoplasms, Experimental/genetics ; Phenotype ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Protein Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins p21(ras)/genetics
Chemical Substances	Drosophila Proteins ; KRAS protein, human ; Protein Kinases (EC 2.7.-) ; LKB1 protein, Drosophila (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; STK11 protein, human (EC 2.7.11.1) ; Calcium-Calmodulin-Dependent Protein Kinases (EC 2.7.11.17) ; AMP-Activated Protein Kinase Kinases (EC 2.7.11.3) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2021-01-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-01663-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The effect of human immunodeficiency virus infection on adverse events during treatment of drug-resistant tuberculosis

Gilbert Lazarus / Kevin Tjoa / Anthony William Brian Iskandar / Melva Louisa / Evans L Sagwa / Nesri Padayatchi / Vivian Soetikno

PLoS ONE, Vol 16, Iss 3, p e

A systematic review and meta-analysis.

2021 Volume 0248017

Abstract: Background Adverse events (AEs) during drug-resistant tuberculosis (DR-TB) treatment, especially with human immunodeficiency virus (HIV) co-infection, remains a major threat to poor DR-TB treatment adherence and outcomes. This meta-analysis aims to ... ...

Abstract	Background Adverse events (AEs) during drug-resistant tuberculosis (DR-TB) treatment, especially with human immunodeficiency virus (HIV) co-infection, remains a major threat to poor DR-TB treatment adherence and outcomes. This meta-analysis aims to investigate the effect of HIV infection on the development of AEs during DR-TB treatment. Methods Eligible studies evaluating the association between HIV seropositivity and risks of AE occurrence in DR-TB patients were included in this systematic review. Interventional and observational studies were assessed for risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention and Newcastle-Ottawa Scale tool, respectively. Random-effects meta-analysis was performed to estimate the pooled risk ratio (RR) along with their 95% confidence intervals (CIs). Results A total of 37 studies involving 8657 patients were included in this systematic review. We discovered that HIV infection independently increased the risk of developing AEs in DR-TB patients by 12% (RR 1.12 [95% CI: 1.02-1.22]; I2 = 0%, p = 0.75). In particular, the risks were more accentuated in the development of hearing loss (RR 1.44 [95% CI: 1.18-1.75]; I2 = 60%), nephrotoxicity (RR 2.45 [95% CI: 1.20-4.98], I2 = 0%), and depression (RR 3.53 [95% CI: 1.38-9.03]; I2 = 0%). Although our findings indicated that the augmented risk was primarily driven by antiretroviral drug usage rather than HIV-related immunosuppression, further studies investigating their independent effects are required to confirm our findings. Conclusion HIV co-infection independently increased the risk of developing AEs during DR-TB treatment. Increased pharmacovigilance through routine assessments of audiological, renal, and mental functions are strongly encouraged to enable prompt diagnosis and treatment in patients experiencing AEs during concomitant DR-TB and HIV treatment.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protocol for the CONNECT project: a mixed methods study investigating patient preferences for communication technology use in orthopaedic rehabilitation consultations.

Gilbert, Anthony William / Jones, Jeremy / Stokes, Maria / Mentzakis, Emmanouil / May, Carl R

BMJ open

2019 Volume 9, Issue 12, Page(s) e035210

Abstract: Introduction: Technology has been placed at the centre of global health policy and has been cited as having the potential to increase efficiency and remove geographical boundaries for patients to access care. Communication technology may support ... ...

Abstract	Introduction: Technology has been placed at the centre of global health policy and has been cited as having the potential to increase efficiency and remove geographical boundaries for patients to access care. Communication technology may support patients with orthopaedic problems, which is one of the leading causes of disability worldwide. There are several examples of technology being used in clinical research, although uptake in practice remains low. An understanding of patient preferences will support the design of a communication technology supported treatment pathway for patients undergoing orthopaedic rehabilitation. Methods and analysis: This mixed methods project will be conducted in four phases. In phase I, a systematic review of qualitative studies reporting communication technology use for orthopaedic rehabilitation will be conducted to devise a taxonomy of tasks patients' face when using these technologies to access their care. In phase II, qualitative interviews will investigate how the work of being a patient changes during face-to-face and communication technology consultations and how these changes influence preference. In phase III, a discrete choice experiment will investigate the factors that influence preferences for the use of communication technology for orthopaedic rehabilitation consultations. Phase IV will be a practical application of these results. We will design a 'minimally disruptive' communication technology supported pathway for patients undergoing orthopaedic rehabilitation. Ethics and dissemination: The design of a pathway and underpinning patient preference will assist in understanding factors that might influence technology implementation for clinical care. This study requires ethical approval for phases II, III and IV. Approvals have been received for phase II (approval received on 4 December 2016 from the South Central-Oxford C Research Ethics Committee (IRAS ID: 255172, REC Reference 18/SC/0663)) and phase III (approval received on 18 October 2019 from the London-Hampstead Research Ethics Committee (IRAS ID: 248064, REC Reference 19/LO/1586)) and will be sought for phase IV. All participants will provide informed written consent prior to being enrolled onto the study. Prospero registration number: CRD42018100896.
MeSH term(s)	Communication ; Humans ; Information Technology ; Musculoskeletal Diseases/rehabilitation ; Patient Preference ; Remote Consultation ; Research Design
Language	English
Publishing date	2019-12-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2019-035210
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Article ; Online: The effect of human immunodeficiency virus infection on adverse events during treatment of drug-resistant tuberculosis: A systematic review and meta-analysis.

Lazarus, Gilbert / Tjoa, Kevin / Iskandar, Anthony William Brian / Louisa, Melva / Sagwa, Evans L / Padayatchi, Nesri / Soetikno, Vivian

PloS one

2021 Volume 16, Issue 3, Page(s) e0248017

Abstract: Background: Adverse events (AEs) during drug-resistant tuberculosis (DR-TB) treatment, especially with human immunodeficiency virus (HIV) co-infection, remains a major threat to poor DR-TB treatment adherence and outcomes. This meta-analysis aims to ... ...

Abstract	Background: Adverse events (AEs) during drug-resistant tuberculosis (DR-TB) treatment, especially with human immunodeficiency virus (HIV) co-infection, remains a major threat to poor DR-TB treatment adherence and outcomes. This meta-analysis aims to investigate the effect of HIV infection on the development of AEs during DR-TB treatment. Methods: Eligible studies evaluating the association between HIV seropositivity and risks of AE occurrence in DR-TB patients were included in this systematic review. Interventional and observational studies were assessed for risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention and Newcastle-Ottawa Scale tool, respectively. Random-effects meta-analysis was performed to estimate the pooled risk ratio (RR) along with their 95% confidence intervals (CIs). Results: A total of 37 studies involving 8657 patients were included in this systematic review. We discovered that HIV infection independently increased the risk of developing AEs in DR-TB patients by 12% (RR 1.12 [95% CI: 1.02-1.22]; I2 = 0%, p = 0.75). In particular, the risks were more accentuated in the development of hearing loss (RR 1.44 [95% CI: 1.18-1.75]; I2 = 60%), nephrotoxicity (RR 2.45 [95% CI: 1.20-4.98], I2 = 0%), and depression (RR 3.53 [95% CI: 1.38-9.03]; I2 = 0%). Although our findings indicated that the augmented risk was primarily driven by antiretroviral drug usage rather than HIV-related immunosuppression, further studies investigating their independent effects are required to confirm our findings. Conclusion: HIV co-infection independently increased the risk of developing AEs during DR-TB treatment. Increased pharmacovigilance through routine assessments of audiological, renal, and mental functions are strongly encouraged to enable prompt diagnosis and treatment in patients experiencing AEs during concomitant DR-TB and HIV treatment.
MeSH term(s)	Antitubercular Agents/adverse effects ; Antitubercular Agents/therapeutic use ; Depression/chemically induced ; Drug-Related Side Effects and Adverse Reactions/etiology ; HIV Infections/complications ; Hearing Loss/chemically induced ; Humans ; Renal Insufficiency/chemically induced ; Tuberculosis, Multidrug-Resistant/complications ; Tuberculosis, Multidrug-Resistant/drug therapy
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2021-03-04
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0248017
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Article ; Online: The level of oncogenic Ras determines the malignant transformation of Lkb1 mutant tissue in vivo

Briana Rackley / Chang-Soo Seong / Evan Kiely / Rebecca E. Parker / Manali Rupji / Bhakti Dwivedi / John M. Heddleston / William Giang / Neil Anthony / Teng-Leong Chew / Melissa Gilbert-Ross

Communications Biology, Vol 4, Iss 1, Pp 1-

2021 Volume 12

Abstract: Rackley, Seong et al use a Drosophila model of Ras/Lkb1 mutant carcinoma to show that high levels of the KRAS oncogene drive the malignant transformation of LKB1 mutant tissue. This pathway could be used as a target for future therapies that aim to treat ...

Abstract	Rackley, Seong et al use a Drosophila model of Ras/Lkb1 mutant carcinoma to show that high levels of the KRAS oncogene drive the malignant transformation of LKB1 mutant tissue. This pathway could be used as a target for future therapies that aim to treat RAS-driven tumours.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology

Hills, Rory A / Tan, Tiong K / Cohen, Alexander A / Keefe, Jennifer R / Keeble, Anthony H / Gnanapragasam, Priyanthi NP / Storm, Kaya N / Hill, Michelle L / Liu, Sai / Gilbert-Jaramillo, Javier / Afzal, Madeeha / Napier, Amy / James, William S / Bjorkman, Pamela J / Townsend, Alain R / Howarth, Mark

bioRxiv

Abstract	Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection.
Keywords	covid19
Language	English
Publishing date	2023-02-24
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.02.24.529520
Database	COVID19

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