Swapnil Kamble | Savitribai Phule Pune University (original) (raw)

Papers by Swapnil Kamble

Research paper thumbnail of Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers

Journal of Clinical Medicine, 2019

Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a ... more Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a pertinent approach in improving prognosis of this highly heterogeneous disease. Enabling the same necessitates identification of class-specific biomarkers and their robust detection in the clinic. We have earlier resolved three discrete molecular HGSC classes associated with distinct functional behavior based on their gene expression patterns, biological networks, and pathways. An important difference revealed was that Class 1 is likely to exhibit cooperative cell migration (CCM), Class 2 undergoes epithelial to mesenchymal transition (EMT), while Class 3 is possibly capable of both modes of migration. In the present study, we define clinical stratification of HGSC tumors through the establishment of standard operating procedures for immunohistochemistry and histochemistry based detection of a panel of biomarkers including TCF21, E-cadherin, PARP1, Slug, AnnexinA2, and hyaluronan. Furthe...

Research paper thumbnail of Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases

Clinical Cancer Research, 2013

Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) c... more Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active invasion and metastases. Experimental Design: We explored this theme toward tumor classification through two approaches of gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii) resolution of independent weighted correlation networks. Further identification of appropriate cell and xenograft models was carried out for resolution of class-specific biologic functions. Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence, cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors. Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial-mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix-EMT-driven invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further validation of these etiologies could define a new therapeutic framework for disease management. Clin Cancer Res; 20(1); 87-99. Ó2013 AACR.

Research paper thumbnail of Evaluation of free radical scavenging with in vitro antiproliferative properties of different extracts of pluchea lanceolata (dc.) oliv. and hiern in cancer cell lines

Pharmacognosy Magazine

Background: Traditional medicinal plants have gained attention as a repository of pharmacological... more Background: Traditional medicinal plants have gained attention as a repository of pharmacologically active molecules. Extracts derived from Pluchea lanceolata (DC.) Oliv. and Hiern are reported to be antimalarial and can protect against chemical-induced neurotoxicity. There is limited research on solvents for extraction of metabolites from stem of P. lanceolata and their anti-cancer potential, which needs to be investigated. Objectives: The objective of the study was to investigate potency of stem powder, extracted in ethanol, methanol, aqueous, and phosphate buffer saline (PBS) solvents, for their phytochemical content, antioxidant potential, and in vitro antiproliferative nature in human cancer cell lines. Materials and Methods: The stem extracts of P. lanceolata were evaluated by phytochemical assays, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging assay, hydrogen peroxide radical scavenging assay, nitric oxide radical scavenging assay, total antioxidant capacity, and assay of reducing power), and antiproliferative potential against cervical (ME-180 and HeLa) and hepatic (HepG2) carcinoma cell lines by MTT assay. Results: Quantification studies showed that the total phenolic content was in the range 7.44–38.91 mg GAE/g of stem extract, while the flavonoids were present in the range 29.05–109.62 mg QE/g of stem extract. Aqueous (DPPH antioxidant capacity assay±PVPP, H2O2 free radical scavenging method-PVPP, assay of reducing power+PVPP, and total antioxidant capacity-PVPP), methanol (H2O2 free radical scavenging method+PVPP, NO radical scavenging assay+PVPP, total antioxidant capacity-PVPP), and ethanol (NO radical scavenging assay-PVPP, assay of reducing power-PVPP) extracts had the highest antioxidant potential in respective assays. MTT findings demonstrated that the aqueous extract was more potent in ME-180 and HepG2 cell lines while the PBS extract caused maximal cytotoxicity in HeLa cells. HepG2 cells were more susceptible than ME-180 and HeLa cells for any of the extract or standard drug evaluated. Conclusion: Aqueous extract of P. lanceolata stem is the most promising extract for further cancer-cell toxicity.

Research paper thumbnail of Assessment of Phytochemicals and Antioxidant Properties of Root Extracts of Rubia cordifolia L. in Different Solvent Systems

Biology and Life Sciences Forum

Rubia cordifolia L. is an important plant used in Ayurvedic and Siddha medicinal systems of India... more Rubia cordifolia L. is an important plant used in Ayurvedic and Siddha medicinal systems of India for treatment of blood disorders. Of all the plant parts, roots of R. cordifolia are the most suitable source of effective secondary metabolites. The present work investigated phytochemical content and antioxidant potential of R. cordifolia root powder extracted in different solvents. Total polyphenols and flavonoids content were estimated. High antioxidant activity was corroborated with DPPH, hydrogen peroxide, nitric oxide, reducing power and total antioxidant assays. Obtained results showed that ethanol extracts were most potent over methanol, aqueous, and PBS extracts for DPPH, hydrogen peroxide, and reducing power assays. In contrast, methanol and aqueous extracts had higher potency in nitric oxide and total antioxidant assays. Encouraging results were obtained for antioxidant activity even upon PVPP treatment that removed the polyphenols from the extracts. The results suggest a po...

Research paper thumbnail of Plant associated fungal endophytes as a source of natural bioactive compounds

Mycology

Endophytes are a potent source of bioactive compounds that mimic plant-based metabolites. The rel... more Endophytes are a potent source of bioactive compounds that mimic plant-based metabolites. The relationship of host plant and endophyte is significantly associated with alteration in fungal colonisation and the extraction of endophyte-derived bioactive compounds. Screening of fungal endophytes and their relationship with host plants is essential for the isolation of bioactive compounds. Numerous bioactive compounds with antioxidant, antimicrobial, anticancer, and immunomodulatory properties are known to be derived from fungal endophytes. Bioinformatics tools along with the latest techniques such as metabolomics, next-generation sequencing, and metagenomics multilocus sequence typing can potentially fill the gaps in fungal endophyte research. The current review article focuses on bioactive compounds derived from plantassociated fungal endophytes and their pharmacological importance. We conclude with the challenges and opportunities in the research area of fungal endophytes.

Research paper thumbnail of Technological Advancements in Bacterial Quorum Sensing Studies in Complex and Heterogeneous Environment

Research paper thumbnail of Technology Platforms for Bioanalysis of Quorum Sensing System and Exploiting It as Biomonitors and Biosensors

Quorum Sensing and its Biotechnological Applications

Research paper thumbnail of Polymeric Bioinks for 3D Hepatic Printing

Chemistry

Three-dimensional (3D) printing techniques have revolutionized the field of tissue engineering. T... more Three-dimensional (3D) printing techniques have revolutionized the field of tissue engineering. This is especially favorable to construct intricate tissues such as liver, as 3D printing allows for the precise delivery of biomaterials, cells and bioactive molecules in complex geometries. Bioinks made of polymers, of both natural and synthetic origin, have been very beneficial to printing soft tissues such as liver. Using polymeric bioinks, 3D hepatic structures are printed with or without cells and biomolecules, and have been used for different tissue engineering applications. In this review, with the introduction to basic 3D printing techniques, we discuss different natural and synthetic polymers including decellularized matrices that have been employed for the 3D bioprinting of hepatic structures. Finally, we focus on recent advances in polymeric bioinks for 3D hepatic printing and their applications. The studies indicate that much work has been devoted to improvising the design, s...

Research paper thumbnail of Gelatin interpenetration in poly N ‐isopropylacrylamide network reduces compressive modulus of scaffold: A property employed to mimic hepatic matrix stiffness

Biotechnology and Bioengineering

Research paper thumbnail of Abstract 2017: Phenotypic plasticity and class switching in ovarian cancer

Research paper thumbnail of Functional Balance between TCF21-Slug defines phenotypic plasticity and sub-classes in high-grade serous ovarian cancer

Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis initiate... more Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis initiated by single cell epithelial to mesenchymal transition or cooperative cell migration (CCM). We identified novel regulatory cross-talks between Tcf21 and Slug in mediating phenotypic and migration plasticity in high-grade serous ovarian adenocarcinoma. Live imaging discerned CCM as being achieved either through rapid cell proliferation or sheet migration. Transitional states were enriched over the rigid epithelial or mesenchymal phenotypes under conditions of environmental stresses. The Tcf21-Slug interplay identified in HGSC tumors through effective stratification of subtypes also contributed to class-switching in response to disease progression or therapy. Our study effectively provides a framework for understanding the relevance of cellular plasticity in situ as a function of two transcription factors.

Research paper thumbnail of Stem cell and cancer stem cell games on the ECM field

Journal of Cancer Stem Cell Research, 2013

Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role playe... more Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role played by their niche that defines a domain-specific identity and functions. The major macromolecular components of any physiological niche are collectively referred to as Extra Cellular Matrix (ECM). Consequently, niche-determined governance of SC-CSC fate(s) is significantly wired by the ECM and its chemical undercurrents, which involve specific signaling cascades driving asymmetrical division and self-renewal, besides maintaining tissue and organ homeostasis. Cell transformation is often associated with variations in ECM composition and dynamics; although the distinction of whether these are a cause or an effect of the process is not clearly established. CSCs regulate altered ECM subtleties; these in turn support disease progression by providing the necessary cues to maintain CSC quiescence and regeneration yet drive cancer metastases. Further, the specific composition of altered ECM plays a critical role in metastatic dissemination and homing to specific secondary sites for tumor regeneration. The present review presents our understanding of modulation of SC and CSC interactions in their respective niche by ECM components, and a complementary focus of intonation of ECM biochemistry by these cells in developing an aberrant phenotype. ABBREVIATIONS Stem cells (SCs); extra cellular matrix (ECM); cancer stem cells (CSCs); epithelial-to-mesenchymal transitions (EMT); basement membrane (BM); interstitial matrix (IM); fibroblast growth factor (FGF); epidermal growth factor (EGF); transforming growth factor-beta (TGFb); platelet-derived growth factor (PDGF), insulin-like growth factor (IGF); tumor necrosis factor a (TNFa); epidermal growth factor receptor (EGFR); matrix metallo-proteinases (MMPs); basic fibroblast growth factor (bFGF); human embryonic stem cells (hESCs); lineage negative (Lin À); reactive oxygen species (ROS); cancer associated fibroblasts (CAFs); osteopontin (OPN), periostin (POSTN), secreted protein acidic and rich in cysteine (SPARC); thrombospondin-1 (TSP-1); hyaluronic acid (HA); sonic hedgehog (SHH); phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), mitogen activated kinase-like protein (MAPK); verb -b2 avian erthroblastic leukemia viral oncogene homolog 2 (ERBB2); hyaluronan-mediated motility receptor (HMMR). CONTENTS 1. Introduction 1.1 Transformation and emergence of CSCs 1.2 Extracellular matrix 1.3 Composition 2. Cross-talk between ECM and stem cells (SC) 2.1 Physical influences of ECM on SC 2.2 Chemical and molecular ECM dynamics governing SC fate 2.2.1 Soluble factors 2.2.2 Small molecules of ECM components 3. Interactions of ECM and CSC: A different ball game? 3.1 Synthesis and regulation 3.2 Role of ECM in cancer niche development and metastases 3.2.1 Cancer niche development 3.2.2 Role of ECM in metastases 3.3 Regulation of quiescence by ECM 3.4 Functionality of CD44, an important CSC marker 4. Concluding remarks and future perspectives References

Research paper thumbnail of Recent technological advancements in stem cell research for targeted therapeutics

Drug Delivery and Translational Research, 2020

Stem cells have characteristic features of self-renewal, pluripotency and differentiation, which ... more Stem cells have characteristic features of self-renewal, pluripotency and differentiation, which are responsible for replenishment of tissue or organ. Stem cells are potentiated as therapeutic tool in drug targeting and regenerative medicine—from curing various neurological diseases and malignancies to congenital diseases. These technological advancements have established stem cells as future of medicine. However, due to ethico-social limitations, the use of embryonic stem cells (ESCs) has been avoided, while physiological availability of adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs) has gained appropriate preference. These iPSCs are very much similar to ESCs in terms of their self-renewal and pluripotency. Here, we have summarized the technologies that have established stem cells isolation, their molecular marker and factors responsible for their maintenance. Different cellular (transcription factors, regulatory proteins, miRNA like miRNA-296, miRNA-145, etc.) and extracellular components transcend stem cell fate. Their identification and characterization involve development and efficient utilization of tools like magnetic activated cell sorting (MACS) and fluorescence activated cell sorting (FACS). Some of the technologies have been patented and spin-off’s based on them have been commercialized. In conclusion, we present the future scope and possibilities that stem cell technologies behold for us.

Research paper thumbnail of Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers

MDPI, 2019

Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a ... more Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted
therapy is a pertinent approach in improving prognosis of this highly heterogeneous disease.
Enabling the same necessitates identification of class-specific biomarkers and their robust detection
in the clinic. We have earlier resolved three discrete molecular HGSC classes associated with distinct
functional behavior based on their gene expression patterns, biological networks, and pathways.
An important difference revealed was that Class 1 is likely to exhibit cooperative cell migration
(CCM), Class 2 undergoes epithelial to mesenchymal transition (EMT), while Class 3 is possibly
capable of both modes of migration. In the present study, we define clinical stratification of HGSC
tumors through the establishment of standard operating procedures for immunohistochemistry
and histochemistry based detection of a panel of biomarkers including TCF21, E-cadherin, PARP1,
Slug, AnnexinA2, and hyaluronan. Further development and application of scoring guidelines
based on expression of this panel in cell line-derived xenografts, commercial tissue microarrays,
and patient tumors led to definitive stratification of samples. Biomarker expression was observed to
vary significantly between primary and metastatic tumors suggesting class switching during disease
progression. Another interesting feature in the study was of enhanced CCM-marker expression in
tumors following disease progression and chemotherapy. These stratification principles and the
new information thus generated is the first step towards class-specific personalized therapies in
the disease.

Research paper thumbnail of Stem Cell and Cancer Stem Cell Games in the ECM Field

Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role playe... more Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role played by their niche that defines a domain-specific identity and functions. The major macromolecular components of any physiological niche are collectively referred to as Extra Cellular Matrix (ECM). Consequently, niche-determined governance of SC-CSC fate(s) is significantly wired by the ECM and its chemical undercurrents, which involve specific signaling cascades driving asymmetrical division and self-renewal, besides maintaining tissue and organ homeostasis. Cell transformation is often associated with variations in ECM composition and dynamics; although the distinction of whether these are a cause or an effect of the process is not clearly established. CSCs regulate altered ECM subtleties; these in turn support disease progression by providing the necessary cues to maintain CSC quiescence and regeneration yet drive cancer metastases. Further, the specific composition of altered ECM plays a critical role in metastatic dissemination and homing to specific secondary sites for tumor regeneration. The present review presents our understanding of modulation of SC and CSC interactions in their respective niche by ECM components, and a complementary focus of intonation of ECM biochemistry by these cells in developing an aberrant phenotype.

Research paper thumbnail of Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases.

AACR, 2014

Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) ... more Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC)
classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active
invasion and metastases.
Experimental Design: We explored this theme toward tumor classification through two approaches of
gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii)
resolution of independent weighted correlation networks. Further identification of appropriate cell and
xenograft models was carried out for resolution of class-specific biologic functions.
Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which
validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence,
cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors.
Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally
random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial–mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant
differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific
markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial
fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix–EMT–driven
invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are
prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further
validation of these etiologies could define a new therapeutic framework for disease management

Books by Swapnil Kamble

Research paper thumbnail of Technology Platforms for Bioanalysis 5 of Quorum Sensing System and Exploiting It as Biomonitors and Biosensors

SpringerNature, 2018

Quorum sensing (QS) is a bacterial signaling phenomenon wherein bacteria regulate gene expression... more Quorum sensing (QS) is a bacterial signaling phenomenon wherein bacteria regulate gene expression as per the concentration of signaling molecule. In the
microbial milieu, bacteria use QS to sense their immediate environment and inturn adjust QS genes. Our knowledge of this continuous process of biosensing
and biomonitoring of QS signaling molecule and QS circuits has evolved over a
period of time. Herein, we attempt to follow impact of newer bioanalysis techniques in understanding this QS phenomenon based on only recent technology
platforms. Some of the technology platforms are at proof of concept stage
wherein feasibility for QS studies is being demonstrated. We attempt to understand the enormous possibilities/potential these technologies withhold.
Advancements in QS systems led researchers to attempt potential application of
QS systems itself as technology platform. In this book chapter, few specifc
applications of QS system towards biosensing and biomonitoring are explored
and covers above mentioned topics in four sections: (a) advanced structural
based techniques involved in QS study (b) advanced biosensing and biomonitoring technologies (c) microarray technology (d) QS technologies for biosensing
and biomonitoring activity. Specifc examples are elaborated in details and for
comprehensive reading on technology platform reader could refer to the references. In summary, advanced technology towards bioanalysis and applications of
QS itself as biosensing and biomonitoring technology are discussed. The critical
analysis, current trends, potential technology applications and the path forward
are touched upon in key opinion and conclusion.

Research paper thumbnail of Technological Developments in Quorum Sensing and Its Inhibition for Medical Applications

SpringerNature, 2018

Recent years have seen great advances in utilizing quorum sensing (QS) and its inhibition, includ... more Recent years have seen great advances in utilizing quorum sensing (QS) and its inhibition, including application of X-ray crystallography, and genetic engineering to improve and develop an array of analytical tools for medical applications. Through utilization of X-ray crystallography to computational approaches, our understanding of QS and quorum sensing inhibition (QSIn) has grown by leaps. Bacterial circuitries are usually characterized by high specificity, selectivity and sensitivity, and thus suggest applications leading to low cost, min-iaturization of circuitry for portable equipment and potential multiplexing. This review is intended to give its reader an overview of technologies based on QS and QSIn for medical use. The sections: techniques and technology platforms/proto-cols towards discovery and development of quorum sensing inhibitor (QSI), the advancement in technology towards theragnostic applications and technology enabled development of QS and QSIn as an anti-virulence strategy are aimed to provide current research insights. Specifically, we examine screening of pathogens using aptamers, biofilm prevention, vaccine development and treatment of infections and cancer.

Research paper thumbnail of Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers

Journal of Clinical Medicine, 2019

Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a ... more Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a pertinent approach in improving prognosis of this highly heterogeneous disease. Enabling the same necessitates identification of class-specific biomarkers and their robust detection in the clinic. We have earlier resolved three discrete molecular HGSC classes associated with distinct functional behavior based on their gene expression patterns, biological networks, and pathways. An important difference revealed was that Class 1 is likely to exhibit cooperative cell migration (CCM), Class 2 undergoes epithelial to mesenchymal transition (EMT), while Class 3 is possibly capable of both modes of migration. In the present study, we define clinical stratification of HGSC tumors through the establishment of standard operating procedures for immunohistochemistry and histochemistry based detection of a panel of biomarkers including TCF21, E-cadherin, PARP1, Slug, AnnexinA2, and hyaluronan. Furthe...

Research paper thumbnail of Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases

Clinical Cancer Research, 2013

Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) c... more Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active invasion and metastases. Experimental Design: We explored this theme toward tumor classification through two approaches of gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii) resolution of independent weighted correlation networks. Further identification of appropriate cell and xenograft models was carried out for resolution of class-specific biologic functions. Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence, cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors. Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial-mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix-EMT-driven invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further validation of these etiologies could define a new therapeutic framework for disease management. Clin Cancer Res; 20(1); 87-99. Ó2013 AACR.

Research paper thumbnail of Evaluation of free radical scavenging with in vitro antiproliferative properties of different extracts of pluchea lanceolata (dc.) oliv. and hiern in cancer cell lines

Pharmacognosy Magazine

Background: Traditional medicinal plants have gained attention as a repository of pharmacological... more Background: Traditional medicinal plants have gained attention as a repository of pharmacologically active molecules. Extracts derived from Pluchea lanceolata (DC.) Oliv. and Hiern are reported to be antimalarial and can protect against chemical-induced neurotoxicity. There is limited research on solvents for extraction of metabolites from stem of P. lanceolata and their anti-cancer potential, which needs to be investigated. Objectives: The objective of the study was to investigate potency of stem powder, extracted in ethanol, methanol, aqueous, and phosphate buffer saline (PBS) solvents, for their phytochemical content, antioxidant potential, and in vitro antiproliferative nature in human cancer cell lines. Materials and Methods: The stem extracts of P. lanceolata were evaluated by phytochemical assays, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging assay, hydrogen peroxide radical scavenging assay, nitric oxide radical scavenging assay, total antioxidant capacity, and assay of reducing power), and antiproliferative potential against cervical (ME-180 and HeLa) and hepatic (HepG2) carcinoma cell lines by MTT assay. Results: Quantification studies showed that the total phenolic content was in the range 7.44–38.91 mg GAE/g of stem extract, while the flavonoids were present in the range 29.05–109.62 mg QE/g of stem extract. Aqueous (DPPH antioxidant capacity assay±PVPP, H2O2 free radical scavenging method-PVPP, assay of reducing power+PVPP, and total antioxidant capacity-PVPP), methanol (H2O2 free radical scavenging method+PVPP, NO radical scavenging assay+PVPP, total antioxidant capacity-PVPP), and ethanol (NO radical scavenging assay-PVPP, assay of reducing power-PVPP) extracts had the highest antioxidant potential in respective assays. MTT findings demonstrated that the aqueous extract was more potent in ME-180 and HepG2 cell lines while the PBS extract caused maximal cytotoxicity in HeLa cells. HepG2 cells were more susceptible than ME-180 and HeLa cells for any of the extract or standard drug evaluated. Conclusion: Aqueous extract of P. lanceolata stem is the most promising extract for further cancer-cell toxicity.

Research paper thumbnail of Assessment of Phytochemicals and Antioxidant Properties of Root Extracts of Rubia cordifolia L. in Different Solvent Systems

Biology and Life Sciences Forum

Rubia cordifolia L. is an important plant used in Ayurvedic and Siddha medicinal systems of India... more Rubia cordifolia L. is an important plant used in Ayurvedic and Siddha medicinal systems of India for treatment of blood disorders. Of all the plant parts, roots of R. cordifolia are the most suitable source of effective secondary metabolites. The present work investigated phytochemical content and antioxidant potential of R. cordifolia root powder extracted in different solvents. Total polyphenols and flavonoids content were estimated. High antioxidant activity was corroborated with DPPH, hydrogen peroxide, nitric oxide, reducing power and total antioxidant assays. Obtained results showed that ethanol extracts were most potent over methanol, aqueous, and PBS extracts for DPPH, hydrogen peroxide, and reducing power assays. In contrast, methanol and aqueous extracts had higher potency in nitric oxide and total antioxidant assays. Encouraging results were obtained for antioxidant activity even upon PVPP treatment that removed the polyphenols from the extracts. The results suggest a po...

Research paper thumbnail of Plant associated fungal endophytes as a source of natural bioactive compounds

Mycology

Endophytes are a potent source of bioactive compounds that mimic plant-based metabolites. The rel... more Endophytes are a potent source of bioactive compounds that mimic plant-based metabolites. The relationship of host plant and endophyte is significantly associated with alteration in fungal colonisation and the extraction of endophyte-derived bioactive compounds. Screening of fungal endophytes and their relationship with host plants is essential for the isolation of bioactive compounds. Numerous bioactive compounds with antioxidant, antimicrobial, anticancer, and immunomodulatory properties are known to be derived from fungal endophytes. Bioinformatics tools along with the latest techniques such as metabolomics, next-generation sequencing, and metagenomics multilocus sequence typing can potentially fill the gaps in fungal endophyte research. The current review article focuses on bioactive compounds derived from plantassociated fungal endophytes and their pharmacological importance. We conclude with the challenges and opportunities in the research area of fungal endophytes.

Research paper thumbnail of Technological Advancements in Bacterial Quorum Sensing Studies in Complex and Heterogeneous Environment

Research paper thumbnail of Technology Platforms for Bioanalysis of Quorum Sensing System and Exploiting It as Biomonitors and Biosensors

Quorum Sensing and its Biotechnological Applications

Research paper thumbnail of Polymeric Bioinks for 3D Hepatic Printing

Chemistry

Three-dimensional (3D) printing techniques have revolutionized the field of tissue engineering. T... more Three-dimensional (3D) printing techniques have revolutionized the field of tissue engineering. This is especially favorable to construct intricate tissues such as liver, as 3D printing allows for the precise delivery of biomaterials, cells and bioactive molecules in complex geometries. Bioinks made of polymers, of both natural and synthetic origin, have been very beneficial to printing soft tissues such as liver. Using polymeric bioinks, 3D hepatic structures are printed with or without cells and biomolecules, and have been used for different tissue engineering applications. In this review, with the introduction to basic 3D printing techniques, we discuss different natural and synthetic polymers including decellularized matrices that have been employed for the 3D bioprinting of hepatic structures. Finally, we focus on recent advances in polymeric bioinks for 3D hepatic printing and their applications. The studies indicate that much work has been devoted to improvising the design, s...

Research paper thumbnail of Gelatin interpenetration in poly N ‐isopropylacrylamide network reduces compressive modulus of scaffold: A property employed to mimic hepatic matrix stiffness

Biotechnology and Bioengineering

Research paper thumbnail of Abstract 2017: Phenotypic plasticity and class switching in ovarian cancer

Research paper thumbnail of Functional Balance between TCF21-Slug defines phenotypic plasticity and sub-classes in high-grade serous ovarian cancer

Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis initiate... more Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis initiated by single cell epithelial to mesenchymal transition or cooperative cell migration (CCM). We identified novel regulatory cross-talks between Tcf21 and Slug in mediating phenotypic and migration plasticity in high-grade serous ovarian adenocarcinoma. Live imaging discerned CCM as being achieved either through rapid cell proliferation or sheet migration. Transitional states were enriched over the rigid epithelial or mesenchymal phenotypes under conditions of environmental stresses. The Tcf21-Slug interplay identified in HGSC tumors through effective stratification of subtypes also contributed to class-switching in response to disease progression or therapy. Our study effectively provides a framework for understanding the relevance of cellular plasticity in situ as a function of two transcription factors.

Research paper thumbnail of Stem cell and cancer stem cell games on the ECM field

Journal of Cancer Stem Cell Research, 2013

Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role playe... more Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role played by their niche that defines a domain-specific identity and functions. The major macromolecular components of any physiological niche are collectively referred to as Extra Cellular Matrix (ECM). Consequently, niche-determined governance of SC-CSC fate(s) is significantly wired by the ECM and its chemical undercurrents, which involve specific signaling cascades driving asymmetrical division and self-renewal, besides maintaining tissue and organ homeostasis. Cell transformation is often associated with variations in ECM composition and dynamics; although the distinction of whether these are a cause or an effect of the process is not clearly established. CSCs regulate altered ECM subtleties; these in turn support disease progression by providing the necessary cues to maintain CSC quiescence and regeneration yet drive cancer metastases. Further, the specific composition of altered ECM plays a critical role in metastatic dissemination and homing to specific secondary sites for tumor regeneration. The present review presents our understanding of modulation of SC and CSC interactions in their respective niche by ECM components, and a complementary focus of intonation of ECM biochemistry by these cells in developing an aberrant phenotype. ABBREVIATIONS Stem cells (SCs); extra cellular matrix (ECM); cancer stem cells (CSCs); epithelial-to-mesenchymal transitions (EMT); basement membrane (BM); interstitial matrix (IM); fibroblast growth factor (FGF); epidermal growth factor (EGF); transforming growth factor-beta (TGFb); platelet-derived growth factor (PDGF), insulin-like growth factor (IGF); tumor necrosis factor a (TNFa); epidermal growth factor receptor (EGFR); matrix metallo-proteinases (MMPs); basic fibroblast growth factor (bFGF); human embryonic stem cells (hESCs); lineage negative (Lin À); reactive oxygen species (ROS); cancer associated fibroblasts (CAFs); osteopontin (OPN), periostin (POSTN), secreted protein acidic and rich in cysteine (SPARC); thrombospondin-1 (TSP-1); hyaluronic acid (HA); sonic hedgehog (SHH); phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), mitogen activated kinase-like protein (MAPK); verb -b2 avian erthroblastic leukemia viral oncogene homolog 2 (ERBB2); hyaluronan-mediated motility receptor (HMMR). CONTENTS 1. Introduction 1.1 Transformation and emergence of CSCs 1.2 Extracellular matrix 1.3 Composition 2. Cross-talk between ECM and stem cells (SC) 2.1 Physical influences of ECM on SC 2.2 Chemical and molecular ECM dynamics governing SC fate 2.2.1 Soluble factors 2.2.2 Small molecules of ECM components 3. Interactions of ECM and CSC: A different ball game? 3.1 Synthesis and regulation 3.2 Role of ECM in cancer niche development and metastases 3.2.1 Cancer niche development 3.2.2 Role of ECM in metastases 3.3 Regulation of quiescence by ECM 3.4 Functionality of CD44, an important CSC marker 4. Concluding remarks and future perspectives References

Research paper thumbnail of Recent technological advancements in stem cell research for targeted therapeutics

Drug Delivery and Translational Research, 2020

Stem cells have characteristic features of self-renewal, pluripotency and differentiation, which ... more Stem cells have characteristic features of self-renewal, pluripotency and differentiation, which are responsible for replenishment of tissue or organ. Stem cells are potentiated as therapeutic tool in drug targeting and regenerative medicine—from curing various neurological diseases and malignancies to congenital diseases. These technological advancements have established stem cells as future of medicine. However, due to ethico-social limitations, the use of embryonic stem cells (ESCs) has been avoided, while physiological availability of adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs) has gained appropriate preference. These iPSCs are very much similar to ESCs in terms of their self-renewal and pluripotency. Here, we have summarized the technologies that have established stem cells isolation, their molecular marker and factors responsible for their maintenance. Different cellular (transcription factors, regulatory proteins, miRNA like miRNA-296, miRNA-145, etc.) and extracellular components transcend stem cell fate. Their identification and characterization involve development and efficient utilization of tools like magnetic activated cell sorting (MACS) and fluorescence activated cell sorting (FACS). Some of the technologies have been patented and spin-off’s based on them have been commercialized. In conclusion, we present the future scope and possibilities that stem cell technologies behold for us.

Research paper thumbnail of Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers

MDPI, 2019

Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted therapy is a ... more Molecular stratification of high-grade serous ovarian carcinoma (HGSC) for targeted
therapy is a pertinent approach in improving prognosis of this highly heterogeneous disease.
Enabling the same necessitates identification of class-specific biomarkers and their robust detection
in the clinic. We have earlier resolved three discrete molecular HGSC classes associated with distinct
functional behavior based on their gene expression patterns, biological networks, and pathways.
An important difference revealed was that Class 1 is likely to exhibit cooperative cell migration
(CCM), Class 2 undergoes epithelial to mesenchymal transition (EMT), while Class 3 is possibly
capable of both modes of migration. In the present study, we define clinical stratification of HGSC
tumors through the establishment of standard operating procedures for immunohistochemistry
and histochemistry based detection of a panel of biomarkers including TCF21, E-cadherin, PARP1,
Slug, AnnexinA2, and hyaluronan. Further development and application of scoring guidelines
based on expression of this panel in cell line-derived xenografts, commercial tissue microarrays,
and patient tumors led to definitive stratification of samples. Biomarker expression was observed to
vary significantly between primary and metastatic tumors suggesting class switching during disease
progression. Another interesting feature in the study was of enhanced CCM-marker expression in
tumors following disease progression and chemotherapy. These stratification principles and the
new information thus generated is the first step towards class-specific personalized therapies in
the disease.

Research paper thumbnail of Stem Cell and Cancer Stem Cell Games in the ECM Field

Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role playe... more Stem cell (SC) and cancer stem cell (CSC) regulation is congregated around the dynamic role played by their niche that defines a domain-specific identity and functions. The major macromolecular components of any physiological niche are collectively referred to as Extra Cellular Matrix (ECM). Consequently, niche-determined governance of SC-CSC fate(s) is significantly wired by the ECM and its chemical undercurrents, which involve specific signaling cascades driving asymmetrical division and self-renewal, besides maintaining tissue and organ homeostasis. Cell transformation is often associated with variations in ECM composition and dynamics; although the distinction of whether these are a cause or an effect of the process is not clearly established. CSCs regulate altered ECM subtleties; these in turn support disease progression by providing the necessary cues to maintain CSC quiescence and regeneration yet drive cancer metastases. Further, the specific composition of altered ECM plays a critical role in metastatic dissemination and homing to specific secondary sites for tumor regeneration. The present review presents our understanding of modulation of SC and CSC interactions in their respective niche by ECM components, and a complementary focus of intonation of ECM biochemistry by these cells in developing an aberrant phenotype.

Research paper thumbnail of Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases.

AACR, 2014

Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) ... more Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC)
classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active
invasion and metastases.
Experimental Design: We explored this theme toward tumor classification through two approaches of
gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii)
resolution of independent weighted correlation networks. Further identification of appropriate cell and
xenograft models was carried out for resolution of class-specific biologic functions.
Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which
validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence,
cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors.
Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally
random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial–mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant
differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific
markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial
fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix–EMT–driven
invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are
prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further
validation of these etiologies could define a new therapeutic framework for disease management

Research paper thumbnail of Technology Platforms for Bioanalysis 5 of Quorum Sensing System and Exploiting It as Biomonitors and Biosensors

SpringerNature, 2018

Quorum sensing (QS) is a bacterial signaling phenomenon wherein bacteria regulate gene expression... more Quorum sensing (QS) is a bacterial signaling phenomenon wherein bacteria regulate gene expression as per the concentration of signaling molecule. In the
microbial milieu, bacteria use QS to sense their immediate environment and inturn adjust QS genes. Our knowledge of this continuous process of biosensing
and biomonitoring of QS signaling molecule and QS circuits has evolved over a
period of time. Herein, we attempt to follow impact of newer bioanalysis techniques in understanding this QS phenomenon based on only recent technology
platforms. Some of the technology platforms are at proof of concept stage
wherein feasibility for QS studies is being demonstrated. We attempt to understand the enormous possibilities/potential these technologies withhold.
Advancements in QS systems led researchers to attempt potential application of
QS systems itself as technology platform. In this book chapter, few specifc
applications of QS system towards biosensing and biomonitoring are explored
and covers above mentioned topics in four sections: (a) advanced structural
based techniques involved in QS study (b) advanced biosensing and biomonitoring technologies (c) microarray technology (d) QS technologies for biosensing
and biomonitoring activity. Specifc examples are elaborated in details and for
comprehensive reading on technology platform reader could refer to the references. In summary, advanced technology towards bioanalysis and applications of
QS itself as biosensing and biomonitoring technology are discussed. The critical
analysis, current trends, potential technology applications and the path forward
are touched upon in key opinion and conclusion.

Research paper thumbnail of Technological Developments in Quorum Sensing and Its Inhibition for Medical Applications

SpringerNature, 2018

Recent years have seen great advances in utilizing quorum sensing (QS) and its inhibition, includ... more Recent years have seen great advances in utilizing quorum sensing (QS) and its inhibition, including application of X-ray crystallography, and genetic engineering to improve and develop an array of analytical tools for medical applications. Through utilization of X-ray crystallography to computational approaches, our understanding of QS and quorum sensing inhibition (QSIn) has grown by leaps. Bacterial circuitries are usually characterized by high specificity, selectivity and sensitivity, and thus suggest applications leading to low cost, min-iaturization of circuitry for portable equipment and potential multiplexing. This review is intended to give its reader an overview of technologies based on QS and QSIn for medical use. The sections: techniques and technology platforms/proto-cols towards discovery and development of quorum sensing inhibitor (QSI), the advancement in technology towards theragnostic applications and technology enabled development of QS and QSIn as an anti-virulence strategy are aimed to provide current research insights. Specifically, we examine screening of pathogens using aptamers, biofilm prevention, vaccine development and treatment of infections and cancer.