Prajna Mishra - Academia.edu (original) (raw)

Papers by Prajna Mishra

Head & Neck

Cisplatin‐resistant oral squamous cell carcinoma (OSCC) cells acquire stem‐like characteristics a... more Cisplatin‐resistant oral squamous cell carcinoma (OSCC) cells acquire stem‐like characteristics and are difficult to treat. Nanog is a transcription factor and needed for maintenance of pluripotency, but its transcription‐promoting role in OSCC progression and cisplatin resistance is poorly understood.

International Immunopharmacology

Journal of Macromolecular Science, Part A

ABSTRACT Poly(ethylene glycol)-poly(lactic acid) copolymer, prepared by ring opening polymerizati... more ABSTRACT Poly(ethylene glycol)-poly(lactic acid) copolymer, prepared by ring opening polymerization, was used as a single platform to co-deliver both hydrophilic doxorubicin and hydrophobic docetaxel (DTX) in a simulated physiological environment. The average size of the negatively charged drug loaded polymeric micelles were found to be 293 nm. The drug loading (%) and encapsulation efficiency (%) were calculated to be 1.21 and 59.0, respectively. The in vitro cytotoxicity test using MCF7 breast cancer cells was conducted using 1 × 104 cells in 10% FBS and 1% antibiotic, and the absorbance of formazan was evaluated at 570 nm. Cell growth inhibition by MTT assay showed viability of 33% of the MCF7 cells after treatment with drug-loaded micelles for 48 h. Controlled release of drugs from the polymeric micelles indicated a burst release effect initially; whereas, 98% of drug could be released at pH 7.4 within a time period of 96 h. Time period for drug release shorten to 48 h only in simulated mild acidic pH (5.4) condition. The in vitro drug release study from micelles indicated synergistic cytotoxicity effect in human metastatic breast cancer MCF7 cell.

Oral Oncology

The cell-surface glycoprotein CD44 is an important oral cancer stem cell (OCSC) marker and plays ... more The cell-surface glycoprotein CD44 is an important oral cancer stem cell (OCSC) marker and plays significant role in oral squamous cell carcinoma (OSCC) aggressiveness, however, the regulation of CD44 is incompletely understood. In the present study, 145 fresh human OSCC tissue specimens, including 18 adjacent normal, 42 noninvasive (N0), 53 invasive tumor samples (N) and 32 chemo-radiation resistant samples (RCRT), were included. The expression of CD44 standard (CD44s) and variants (CD44v4, CD44v6); the activation of pERK1/2, GSK3β, NICD (Notch) pathways; the cell viability; and the MMP-9/-2 activity were assessed using RT-PCR, immunohistochemistry, Western blotting, MTT assay and gelatin zymography. OSCC cell lines, including parental (SCC9/SCC4) and Cisplatin-resistant (CisR-SCC9/-SCC4) cells, were used. Knock down of CD44v4/CD44v6 (by siRNA) or inactivation of MAPK/PI3K pathways using specific PD98059/LY294002 was achieved for in vitro analysis of chemoresistance and invasion/migration. Elevated CD44 variants were associated with overall OSCC progression, chemoresistance and invasion. Positive correlations were observed, mainly between the expression of CD44v4 and the activation of ERK1/2 causing chemoresistance, whereas CD44v6 expression and inactivation of GSK3β caused invasiveness of OSCC. Cisplatin resistant, CisR-SCC9/SCC4 cell lines showed OCSC properties. Inhibition of MEK/ERK1/2 by SMI or knock down (KD) of CD44v4 by siRNA reversed cisplatin-resistance, whereas blocking the PI3K/Akt/GSK3β pathway by SMI or KD of CD44v6 isoforms by respective siRNA diminished invasion/metastasis potential. Collectively, our results demonstrated that CD44v4 expression is more linked with ERK1/2 activation and promote cisplatin resistance, whereas CD44v6 expression is associated primarily with PI3K/Akt/GSK3β activation and driving tumor invasion/migration.

International Journal of Polymeric Materials and Polymeric Biomaterials

ABSTRACT Docetaxel (DTX)-loaded poly(ethylene glycol)–poly(D,L-lactide) is prepared by nanoprecip... more ABSTRACT Docetaxel (DTX)-loaded poly(ethylene glycol)–poly(D,L-lactide) is prepared by nanoprecipitation method in the absence of any surfactants. The average particle size of the copolymer was found to be 101 nm. The drug entrapment efficiency (%) and drug loading (%) of polymer were found to be 9.471 ± 0.047 and 94.71 ± 0.466, respectively. The in vitro drug release characteristics show the controlled release of 98% of docetaxel in 72 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis measured in terms of cleaved Poly(ADP-ribose) Polymerase (PARP) and cleaved caspase-3 protein expression shows that the copolymer has better cytotoxicity effect and apoptosis in comparison to free DTX in HeLa cells. GRAPHICAL ABSTRACT

Journal of Biological …, 2009

A delicate balance between cell death and survival pathways maintains normal physiology, which is... more A delicate balance between cell death and survival pathways maintains normal physiology, which is altered in many cancers, shifting the balance toward increased survival. Several studies have established a close connection between the Wnt/␤-catenin pathway and tumorigenesis, aberrant activation of which might contribute toward increased cancer cell growth and survival. Extensive research is underway to identify therapeutic agents that can induce apoptosis specifically in cancer cells with minimal collateral damage to normal cells. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis specifically in tumor cells, many cancer cells develop resistance, which can be overcome by combinatorial treatment with other agents: for example, peroxisome proliferator-activated receptor ␥ (PPAR␥) ligands. To identify the molecular target mediating combinatorial druginduced apoptosis, we focused on ␤-catenin, a protein implicated in oncogenesis. Our results show that co-treatment of TRAIL-resistant cancer cells with TRAIL and the PPAR␥ ligand troglitazone leads to a reduction of ␤-catenin expression, coinciding with maximal apoptosis. Modulation of ␤-catenin levels via ectopic overexpression or small interference RNA-mediated gene silencing modulates drug-induced apoptosis, indicating involvement of ␤-catenin in regulating this pathway. More in-depth studies indicated a post-translational mechanism, independent of glycogen synthase kinase-3␤ activity regulating ␤-catenin expression following combinatorial drug treatment. Furthermore, TRAIL-and troglitazone-induced apoptosis was preceded by a cleavage of ␤-catenin, which was complete in a fully apoptotic population, and was mediated by caspases-3 and-8. These results demonstrate ␤-catenin as a promising new target of drug-induced apoptosis, which can be targeted to sensitize apoptosis-resistant cancer cells.

Molecular Endocrinology, 2010

Gastrin is a gastrointestinal peptide hormone, secreted by the gastric G cells and can exist as a... more Gastrin is a gastrointestinal peptide hormone, secreted by the gastric G cells and can exist as a fully processed amidated form (G17) or as unprocessed forms. All forms of gastrin possess trophic properties towards the gastrointestinal mucosa. An understanding of the signaling pathways involved is important to design therapeutic approaches to target gastrin-mediated cellular events. The studies described here were designed to identify the signaling pathways by which amidated gastrin (G17) mediates cancer cell migration. These studies indicated a time-and dose-dependent increase in gastric cancer cell migration after G17 stimulation, involving cholecystokinin 2 receptor. G17-induced migration was preceded by activation of MAPK pathways and was antagonized after pretreatment with SP600125, a pharmacological inhibitor of c-Jun-NH 2-terminal kinase (JNK) pathway. Knockdown of endogenous JNK1 expression via small interference RNA (JNK1-siRNA) inhibited G17-induced phosphorylation of c-Jun and migration, and overexpression of wild-type JNK1 or constitutive active JNK1 promoted G17-induced migration. Studies designed to identify the MAPK kinase kinase member mediating JNK activation indicated the involvement of mixed lineage kinase-3 (MLK3), which was transiently activated upon G17 treatment. Inhibition of MLK3 pathway via a pan-MLK inhibitor or knockdown of MLK3 expression by MLK3-siRNA antagonized G17-induced migration. Incubation with G17 also resulted in an induction of matrix metalloproteinase 7 promoter activity, which is known to mediate migration and invasion pathways in cancer cells. Modulation of MLK3, JNK1, and c-Jun pathways modulated G17-induced matrix metalloproteinase 7 promoter activation. These studies indicate that the MLK3/JNK1 axis mediates G17-induced gastric cancer cell migration, which can be targeted for designing novel therapeutic strategies for treating gastric malignancies. (Molecular Endocrinology 24: 598-607, 2010) G astrin is a gastrointestinal (GI) peptide hormone, produced by the gastric G cells and is involved in gastric acid secretion. Gastrin mediates its effects via activation of the CCK2 receptor (CCK2R), formerly known as CCKBR (1). Studies over the past two decades have demonstrated a distinct link between gastrin and GI cancer (2, 3). Mature amidated gastrin (G17), as well as its nonamidated precursor, glycine-extended gastrin (G-Gly), can induce growth and expression of growth-promoting genes in various GI cancer cell lines (4-6). The link between gastrin and GI cancer has been later validated by the creation of transgenic animal models overexpressing various forms of gastrin (7). Patients infected with Heliobacter pylori show an increase in their circu

Journal of Molecular Signaling, 2010

BACKGROUND: The gastrointestinal peptide hormone gastrin is known to regulate various cellular pr... more BACKGROUND: The gastrointestinal peptide hormone gastrin is known to regulate various cellular processes including proliferation, migration and metastasis in gastrointestinal (GI) cells. The studies described here were undertaken to elucidate in detail the signaling pathways mediating the migratory responses of amidated gastrin (G17) and to understand the involvement of the serine/threonine kinase Glycogen Synthase Kinase-3 beta (GSK3β) in this. RESULTS:

Asian Journal of Pharmaceutical Sciences, 2015

Advanced drug delivery systems using poly(ethylene glycol) (PEG) is an important development in a... more Advanced drug delivery systems using poly(ethylene glycol) (PEG) is an important development in anti-cancer therapy. PEGylation has the ability to enhance the retention time of the therapeutics like proteins, enzymes small molecular drugs, liposomes and nanoparticles by protecting them against various degrading mechanisms active inside a tissue or cell, which consequently improves their therapeutic potential. PEGylation effectively alters the pharmacokinetics (PK) of a variety of drugs and dramatically improves the pharmaceutical values; recent development of which includes fabrication of stimuli-sensitive polymers/smart polymers and polymeric micelles to cope of with the pathophysiological environment of targeted site with less toxic effects and more effectiveness. This overview discusses PEGylation involving proteins, enzymes, low molecular weight drugs, liposomes and nanoparticles that has been developed, clinically tried for anti-cancer therapy during the last decade.