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Article: Remodeling of Stromal Cells and Immune Landscape in Microenvironment During Tumor Progression.

Arora, Leena / Pal, Durba

2021 Volume 11, Page(s) 596798

Abstract: The molecular understanding of carcinogenesis and tumor progression rests in intra and inter-tumoral heterogeneity. Solid tumors confined with vast diversity of genetic abnormalities, epigenetic modifications, and environmental cues that differ at each ... ...

Abstract	The molecular understanding of carcinogenesis and tumor progression rests in intra and inter-tumoral heterogeneity. Solid tumors confined with vast diversity of genetic abnormalities, epigenetic modifications, and environmental cues that differ at each stage from tumor initiation, progression, and metastasis. Complexity within tumors studied by conventional molecular techniques fails to identify different subclasses in stromal and immune cells in individuals and that affects immunotherapies. Here we focus on diversity of stromal cell population and immune inhabitants, whose subtypes create the complexity of tumor microenvironment (TME), leading primary tumors towards advanced-stage cancers. Recent advances in single-cell sequencing (epitope profiling) approach circumscribes phenotypic markers, molecular pathways, and evolutionary trajectories of an individual cell. We discussed the current knowledge of stromal and immune cell subclasses at different stages of cancer development with the regulatory role of non-coding RNAs. Finally, we reported the current therapeutic options in immunotherapies, advances in therapies targeting heterogeneity, and possible outcomes.
Language	English
Publishing date	2021-03-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.596798
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Article ; Online: Assessment of Mitochondrial Health in Cancer-Associated Fibroblasts Isolated from 3D Multicellular Lung Tumor Spheroids.

Arora, Leena / Kalia, Moyna / Roy, Soumyajit / Pal, Durba

Journal of visualized experiments : JoVE

2022 , Issue 188

Abstract: Cancer-associated fibroblasts (CAFs) are among the most abundant stromal cells present in the tumor microenvironment, facilitating tumor growth and progression. Complexity within the tumor microenvironment, including tumor secretome, low-grade ... ...

Abstract	Cancer-associated fibroblasts (CAFs) are among the most abundant stromal cells present in the tumor microenvironment, facilitating tumor growth and progression. Complexity within the tumor microenvironment, including tumor secretome, low-grade inflammation, hypoxia, and redox imbalance, fosters heterotypic interaction and allows the transformation of inactive resident fibroblasts to become active CAFs. CAFs are metabolically distinguished from normal fibroblasts (NFs) as they are more glycolytically active, produce higher levels of reactive oxygen species (ROS), and overexpress lactate exporter MCT-4, leading to the opening of the mitochondrial permeability transition pore (MPTP). Here a method has been described to analyze the mitochondrial health of activated CAFs isolated from the multicellular 3D tumor spheroids comprising of human lung adenocarcinoma cells (A549), human monocytes (THP-1), and human lung fibroblast cells (MRC5). Tumor spheroids were disintegrated at different time intervals and through magnetic-activated cell sorting, CAFs were isolated. The mitochondrial membrane potential of CAFs was assessed using JC-1 dye, ROS production by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining, and enzyme activity in the isolated CAFs. Analyzing the mitochondrial health of isolated CAFs provides a better understanding of the reverse Warburg effect and can also be applied to study the consequences of CAF mitochondrial changes, such as metabolic fluxes and the corresponding regulatory mechanisms on lung cancer heterogeneity. Thus, the present study advocates an understanding of tumor-stroma interactions on mitochondrial health. It would provide a platform to check mitochondrial-specific drug candidates for their efficacies against CAFs as potential therapeutics in the tumor microenvironment, thereby preventing CAF involvement in lung cancer progression.
MeSH term(s)	Humans ; Cancer-Associated Fibroblasts/pathology ; Reactive Oxygen Species/metabolism ; Lung Neoplasms/pathology ; Fibroblasts/metabolism ; Adenocarcinoma of Lung/pathology ; Tumor Microenvironment
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2022-10-21
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/64315
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Article ; Online: Role of macrophages in cancer progression and targeted immunotherapies.

Arora, Leena / Kalia, Moyna / Pal, Durba

Advances in protein chemistry and structural biology

2022 Volume 135, Page(s) 281–311

Abstract: The vast complexity of the tumor microenvironment (TME) aggrandizes the underlying principles responsible for immune escape, therapy resistance, and treatment failure. The stromal and immune cell population circumjacent to the tumor cells affects the ... ...

Abstract	The vast complexity of the tumor microenvironment (TME) aggrandizes the underlying principles responsible for immune escape, therapy resistance, and treatment failure. The stromal and immune cell population circumjacent to the tumor cells affects the cancer cell cycle leading to tumor progression. Tumor-associated macrophages (TAMs) exhibiting a unique M2 polarization state constitute a significant portion of the TME. They serve as tumor suppressors at early stages and tumor promoters at advanced stages by governing various microenvironmental cues. TAMs secreted various pro-tumoral cytokines, chemokines, and matrix metalloproteases are known to regulate the different cell cycle molecules including checkpoint inhibitors in cancer cells leading to cell cycle progression with faulty cellular components. Moreover, TAMs are well-known immunosuppressors and thereby facilitating the tumor cells' evasion from immune recognition. This chapter will describe the interaction between TAMs and tumor cells, the involvement of TAMs in the regulation of cancer cell progression by controlling cell cycle checkpoints or molecular pathways, and current TAM-based therapies, including restriction of TAM recruitment, anti-survival strategies, or switching polarity. Moreover, this chapter will also emphasize recently developed drug targets and CAR-macrophage cell therapy that restricts tumor progression.
MeSH term(s)	Humans ; Neoplasms/metabolism ; Macrophages ; Immunotherapy ; Cytokines/metabolism ; Tumor Microenvironment
Chemical Substances	Cytokines
Language	English
Publishing date	2022-12-19
Publishing country	Netherlands
Document type	Journal Article
ISSN	1876-1631 ; 1876-1623
ISSN (online)	1876-1631
ISSN	1876-1623
DOI	10.1016/bs.apcsb.2022.11.010
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Article: Immunoengineered MXene nanosystem for mitigation of alloantigen presentation and prevention of transplant vasculopathy.

Yan, Weiang / Rafieerad, Alireza / Alagarsamy, Keshav Narayan / Saleth, Leena Regi / Arora, Rakesh C / Dhingra, Sanjiv

Nano today

2023 Volume 48, Page(s) None

Abstract: MXenes are an emerging class of nanomaterials with significant potential for applications in nanomedicine. Amongst MXene technologies, titanium carbide ( ... ...

Abstract	MXenes are an emerging class of nanomaterials with significant potential for applications in nanomedicine. Amongst MXene technologies, titanium carbide (Ti
Language	English
Publishing date	2023-04-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2224882-1
ISSN	1878-044X ; 1748-0132
ISSN (online)	1878-044X
ISSN	1748-0132
DOI	10.1016/j.nantod.2022.101706
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Article: Evaluation of Reproductive Outcome in Infertile Hypothyroid Women on Thyroxine Therapy.

Wadhwa, Leena / Marghret, K Monica / Arora, Sarika

Journal of human reproductive sciences

2020 Volume 13, Issue 4, Page(s) 272–276

Abstract: Introduction: Thyroid dysfunction is associated with increased risk of infertility. Serum thyroid stimulating hormone (TSH) screening in all women seeking infertility care is recommended and hypothyroid infertile women should be treated with thyroxine ... ...

Abstract	Introduction: Thyroid dysfunction is associated with increased risk of infertility. Serum thyroid stimulating hormone (TSH) screening in all women seeking infertility care is recommended and hypothyroid infertile women should be treated with thyroxine until the preconception serum TSH level is <2.5 mU/l.[1] However, insufficient evidence exist to determine if thyroxine therapy improves fertility in subclinical hypothyroid women who are trying to conceive naturally. Objectives: The objective is to study the effect of thyroxine therapy on reproductive outcome in infertile women with clinical and subclinical hypothyroidism (SCH). Materials and methods: The study is a descriptive cohort study with 72 subjects. Women between 20 and 40 years of age with primary or secondary infertility with hypothyroidism were studied and thyroid profile including free T3, T4, TSH, and thyroid antibodies were done. Thyroxine was given to clinical, subclinical hypothyroid subjects depending on TSH levels such that serum TSH levels are maintained < 2.5 mU/L. Serial thyroid function test was done every 6 weeks until the optimal levels were reached. Once normal TSH levels were reached subjects were followed up for 6 months. Reproductive outcome was analyzed in two groups. Group A included hypothyroid infertile women who conceived and Group B included those who did not conceive following thyroxine therapy. Results: Thirty-eight out of 72 subjects (54%) conceived during thyroxine treatment (Group A) of which 4 cases had miscarriage. Maximum infertile women in Group A (20/38) conceived between 6 and 12 months (52.6%) of thyroxine therapy. Significant decrease was observed in mean TSH levels over a period of 6 months ( Conclusion: Thyroxine therapy enhances fertility in infertile women with clinical and SCH.
Language	English
Publishing date	2020-12-28
Publishing country	India
Document type	Journal Article
ZDB-ID	2418984-4
ISSN	1998-4766 ; 0974-1208
ISSN (online)	1998-4766
ISSN	0974-1208
DOI	10.4103/jhrs.JHRS_14_20
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Article ; Online: Dexamethasone-loaded, injectable pullulan-poly(ethylene glycol) hydrogels for bone tissue regeneration in chronic inflammatory conditions.

Chauhan, Neelam / Gupta, Priya / Arora, Leena / Pal, Durba / Singh, Yashveer

Materials science & engineering. C, Materials for biological applications

2021 Volume 130, Page(s) 112463

Abstract: Chronic inflammation, infection, and fixation stability disrupts bone tissue regeneration by implants. The elevated levels of inflammatory markers and reactive oxygen species (ROS) damage tissues, inhibit osteoblastic differentiation, and promote bone ... ...

Abstract	Chronic inflammation, infection, and fixation stability disrupts bone tissue regeneration by implants. The elevated levels of inflammatory markers and reactive oxygen species (ROS) damage tissues, inhibit osteoblastic differentiation, and promote bone resorption. Activation of local and chronic inflammatory responses due to the implantable biomaterial poses a high risk of implant failure and compromised bone repair in several pathological conditions. Not much progress has been made in the development of biomaterials that can counter inflammation and ROS along with inducing osteogenic activities for managing bone defects/injuries. We have developed, for the first time, injectable polymeric hydrogels by crosslinking oxidized pullulan (OP, 1% w/v) and 8-arm PEG hydrazine (PEG-HY, 10% w/v) using pH-sensitive and dynamic hydrazone linkages at 37 °C in buffer. The hydrogels were loaded with dexamethasone (Dex), an anti-inflammatory corticosteroid and osteogenic inducer, by covalently linking it to PEG-HY by hydrazone linkages, and their morphological, injectability, viscoelastic, self-healing, swelling, and drug-release properties were investigated. The hydrogels provided a pH-sensitive sustained release of PEG-Dex conjugate (3.62 wt%, 9.22 × 10
MeSH term(s)	Animals ; Biocompatible Materials ; Bone Regeneration ; Dexamethasone/pharmacology ; Glucans ; Hydrogels/pharmacology ; Mice ; Osteogenesis ; Polyethylene Glycols
Chemical Substances	Biocompatible Materials ; Glucans ; Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A) ; Dexamethasone (7S5I7G3JQL) ; pullulan (8ZQ0AYU1TT)
Language	English
Publishing date	2021-09-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2012160-X
ISSN	1873-0191 ; 0928-4931
ISSN (online)	1873-0191
ISSN	0928-4931
DOI	10.1016/j.msec.2021.112463
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Article: Development of a Multicellular 3D Tumor Model to Study Cellular Heterogeneity and Plasticity in NSCLC Tumor Microenvironment.

Arora, Leena / Kalia, Moyna / Dasgupta, Suman / Singh, Navneet / Verma, Anita K / Pal, Durba

Frontiers in oncology

2022 Volume 12, Page(s) 881207

Abstract: Heterogeneity is a characteristic feature of solid tumors. Intra-tumor heterogeneity includes phenotypic diversity, epigenetic abnormalities, cell proliferation, and plasticity that eventually drives disease progression. Studying tumor heterogeneity in ... ...

Abstract	Heterogeneity is a characteristic feature of solid tumors. Intra-tumor heterogeneity includes phenotypic diversity, epigenetic abnormalities, cell proliferation, and plasticity that eventually drives disease progression. Studying tumor heterogeneity in 2D culture is challenging as it cannot simulate the microenvironmental features, such as hypoxia, nutrient unavailability, and cell-ECM interactions. We propose the development of multicellular (tri-culture) 3D spheroids using a hanging drop method to study the non-tumorigenic (BEAS-2B) vs. tumorigenic NSCLC (A549/NCI-H460)cells' interaction with lung fibroblasts (MRC-5) and monocytes (THP-1). Unlike the non-tumorigenic model, the tumorigenic 3D spheroids show significant induction of cell proliferation, hypoxia, pluripotency markers, notable activation of cancer-associated fibroblasts, and tumor-associated macrophages. CD68+ macrophages isolated from tumorigenic spheroids exhibited profound induction of phenotypic endothelial characteristics. The results are zebrafish tumor xenograft model and by using human patient samples. This multicellular 3D tumor model is a promising tool to study tumor-stroma interaction and cellular plasticity, targeting tumor heterogeneity, and facilitating cancer therapy success against NSCLC.
Language	English
Publishing date	2022-06-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.881207
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Article: Gene Editing and Crop Improvement Using CRISPR-Cas9 System.

Arora, Leena / Narula, Alka

Frontiers in plant science

2017 Volume 8, Page(s) 1932

Abstract: Advancements in Genome editing technologies have revolutionized the fields of functional genomics and crop improvement. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat)-Cas9 is a multipurpose technology for genetic engineering that ... ...

Abstract	Advancements in Genome editing technologies have revolutionized the fields of functional genomics and crop improvement. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat)-Cas9 is a multipurpose technology for genetic engineering that relies on the complementarity of the guideRNA (gRNA) to a specific sequence and the Cas9 endonuclease activity. It has broadened the agricultural research area, bringing in new opportunities to develop novel plant varieties with deletion of detrimental traits or addition of significant characters. This RNA guided genome editing technology is turning out to be a groundbreaking innovation in distinct branches of plant biology. CRISPR technology is constantly advancing including options for various genetic manipulations like generating knockouts; making precise modifications, multiplex genome engineering, and activation and repression of target genes. The review highlights the progression throughout the CRISPR legacy. We have studied the rapid evolution of CRISPR/Cas9 tools with myriad functionalities, capabilities, and specialized applications. Among varied diligences, plant nutritional improvement, enhancement of plant disease resistance and production of drought tolerant plants are reviewed. The review also includes some information on traditional delivery methods of Cas9-gRNA complexes into plant cells and incorporates the advent of CRISPR ribonucleoproteins (RNPs) that came up as a solution to various limitations that prevailed with plasmid-based CRISPR system.
Language	English
Publishing date	2017-11-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711035-7
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2017.01932
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Article ; Online: Hypoxia-induced miR-210-3p expression in lung adenocarcinoma potentiates tumor development by regulating CCL2-mediated monocyte infiltration.

Arora, Leena / Patra, Debarun / Roy, Soumyajit / Nanda, Sidhanta / Singh, Navneet / Verma, Anita K / Chakraborti, Anuradha / Dasgupta, Suman / Pal, Durba

Molecular oncology

2022

Abstract: In most cancers, tumor hypoxia downregulates the expression of C-C motif chemokine 2 (CCL2), and this downregulation has been implicated in monocyte infiltration and tumor progression; however, the molecular mechanism is yet not clear. We compared non- ... ...

Abstract	In most cancers, tumor hypoxia downregulates the expression of C-C motif chemokine 2 (CCL2), and this downregulation has been implicated in monocyte infiltration and tumor progression; however, the molecular mechanism is yet not clear. We compared non-cancerous and lung-adenocarcinoma human samples for hypoxia-inducible factor 1-alpha (HIF-1A), microRNA-210-3p (mir-210-3p) and CCL2 levels. Mechanistic studies were performed on lung adenocarcinoma cell lines and 3D tumor spheroids to understand the role of hypoxia-induced miR-210-3p in the regulation of CCL2 expression and macrophage polarization. HIF-1 A stabilization increases miR-210-3p levels in lung adenocarcinoma and impairs monocyte infiltration by inhibiting CCL2 expression. Mechanistically, miR-210-3p directly binds to the 3'untranslated region (UTR) of CCL2 mRNA and silences it. Suppressing miR-210-3p substantially downregulates the effect of hypoxia on CCL2 expression. Monocyte migration is significantly hampered in miR-210-3p mimic-transfected HIF-1A silenced cancer cells. In contrast, inhibition of miR-210-3p in HIF-1A-overexpressed cells markedly restored monocyte migration, highlighting a direct link between miR-210-3p level and tumor monocyte burden. Moreover, miR-210-3p inhibition in 3D tumor spheroids promotes monocyte recruitment and skewing towards an anti-tumor M1 phenotype. Anti-hsa-miR-210-3p-locked nucleic acid (LNA) delivery in a lung tumor xenograft zebrafish model caused tumor regression, suggesting that miR-210-3p could be a promising target for immunomodulatory therapeutic strategies against lung adenocarcinoma.
Language	English
Publishing date	2022-06-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13260
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Article ; Online: Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

Nair, M K C / Ahmed, Shabina / Multani, Kawaljit Singh / Mohamed Ismail, P M / Kamath, S S / Dalwai, Samir H / Meenai, Zafar / Suman, Praveen / Seth, Shambhavi / Srivastava, Leena / Srinivasan, Roopa / Lewin, Maria / Sanjay, K / Lal, D V / Udayakumar, N / George, Babu / Koshy, Beena / Deshpande, Leena / Sitaraman, S /

Manju, G E / Unni, Jeeson C / Paul, Abraham K / Chowdhury, Sreetama / Arora, N K / Russell, P S

Indian pediatrics

2024 Volume 61, Issue 1, Page(s) 10–23

Abstract: Justification: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a ... ...

Abstract	Justification: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. Process: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. Objectives: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. Statement: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.
MeSH term(s)	Child ; Humans ; Infant ; Infant, Newborn ; Academies and Institutes ; Early Diagnosis ; India ; Neurodevelopmental Disorders/diagnosis ; Neurodevelopmental Disorders/epidemiology ; Neurodevelopmental Disorders/prevention & control
Language	English
Publishing date	2024-01-03
Publishing country	India
Document type	Journal Article
ZDB-ID	402594-5
ISSN	0974-7559 ; 0019-6061
ISSN (online)	0974-7559
ISSN	0019-6061
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