saurabh singh - Academia.edu (original) (raw)
Papers by saurabh singh
Biosensors & bioelectronics, Jan 15, 2010
Luminescent microspheres encapsulating glucose oxidase have recently been reported as potential i... more Luminescent microspheres encapsulating glucose oxidase have recently been reported as potential implantable sensors, but the operational lifetime of these systems has been limited by enzyme degradation. We report here that the longevity of these enzymatic microparticle-based sensors has been extended by the coimmobilization of glucose oxidase (GOx) and catalase (CAT) into the sensor matrix. A mathematical model was used to compare the response and longevity of the sensors with and without catalase. To experimentally test the longevity, sensors were continuously operated under normoglycemic dermal substrate concentrations and physiological conditions (5.5 mM glucose and 140 M O 2 , 37 • C and pH 7.4). The sensors incorporating CAT were experimentally shown to be ∼5 times more stable than those without CAT; nevertheless, the response of sensors with CAT still changed by approximately 20%, when operated continuously for 7 days. The experimentally determined trends obtained for the variation in sensor response due to enzyme deactivation were in close agreement with modeling predictions, which also revealed a significant apparent loss in enzyme activity upon immobilization. It was further predicted via modeling that by incorporating 0.1 mM each of active GOx and CAT, the sensors will exhibit less than 2% variation in response over 1 month of continuous operation.
Considerable progress has been made in face recognition research over the last decade especially ... more Considerable progress has been made in face recognition research over the last decade especially with the development of powerful models of face appearance (i.e., eigenfaces). Despite the variety of approaches and tools studied, however, face recognition is not accurate or robust enough to be deployed in uncontrolled environments. Recently, a number of studies have shown that infrared (IR) imagery offers a promising alternative to visible imagery due to its relative insensitive to illumination changes. However, IR has other limitations including that it is opaque to glass. As a result, IR imagery is very sensitive to facial occlusion caused by eyeglasses. In this paper, we propose fusing IR with visible images, exploiting the relatively lower sensitivity of visible imagery to occlusions caused by eyeglasses. Two different fusion schemes have been investigated in this study: (1) imagebased fusion performed in the wavelet domain and, (2) feature-based fusion performed in the eigenspace domain. In both cases, we employ Genetic Algorithms (GAs) to find an optimum strategy to perform the fusion. To evaluate and compare the proposed fusion schemes, we have performed extensive recognition experiments using the Equinox face dataset and the popular method of eigenfaces. Our results show substantial improvements in recognition performance overall, suggesting that the idea of fusing IR with visible images for face recognition deserves further consideration.
Controlling cell growth on different surfaces is crucial for many applications. For instance afte... more Controlling cell growth on different surfaces is crucial for many applications. For instance after surgery, unspecific adhesion on exogenous materials can lead to fouling that may result in infections. On the other hand, fast attachment of tissue cells is pivotal for the healing process. Hence, specific regulation of cell adhesion to substrates is a significant task especially in the biomedical
Langmuir : the ACS journal of surfaces and colloids, Jan 25, 2015
The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyeth... more The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyethylenimine (PEI) and polystyrenesulfonate (PSS) films deposited on a single crystal quartz substrate. LbL-deposited nanofilms were investigated by neutron reflectomery (NR) in contact with water in the static and fluid shear stress conditions. The fluid shear stress was applied through a laminar flow of the liquid parallel to the quartz/polymer interface in a custom-built solid-liquid interface cell. The scattering length density profiles obtained from NR results of these polyelectrolyte multilayers (PEM), measured under different shear conditions, showed proportional decrease of volume fraction of water hydrating the polymers. For the highest shear rate applied (ca. 6800 s(-1)) the water volume fraction decreased by approximately 7%. The decrease of the volume fraction of water was homogeneous through the thickness of the film. Since there were not any significant changes in the total polymer thickness, it resulted in negative osmotic pressures in the film. The PEM films were compared with the behavior of thin films of thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) deposited via spin-coating. The PEM and pNIPAM differ in their interactions with water molecules, and they showed opposite behaviors under the fluid shear stress. In both cases the polymer hydration was reversible upon the restoration of static conditions. A theoretical explanation is given to explain this difference in the effect of shear on hydration of polymeric thin films.
Pharmaceutical powder engineering often involves forming interfaces between the drug and a suitab... more Pharmaceutical powder engineering often involves forming interfaces between the drug and a suitable polymer. The structure at the interface plays a critical role in the properties and performance of the composite. However, interface structures have not been well understood due to a lack of suitable characterization tool. In this work, we have used ellipsometry and neutron reflectometry to characterize the structure of such interfaces in detail. Ellipsometry provided a quick estimate of the number of layers and their thicknesses, whereas neutron reflectometry provided richer structural information such as density, thickness, roughness, and intermixing of different layers. The combined information allowed us to develop an accurate model about the layered structure and provided information about intermixing of different layer components. Systematic use of these characterization techniques on several model systems suggests that the nature of the polymer had a small effect on the interfacial structure, while the solvent used in polymer coating had a large effect. These results provide useful information on the efforts of engineering particle properties through the control of the interfacial chemistry.
Journal of biomedicine & biotechnology, 2005
During the early stages of embryogenesis, pluripotent neural crest cells (NCC) are known to migra... more During the early stages of embryogenesis, pluripotent neural crest cells (NCC) are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR). The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.
ABSTRACT A robust and simple method for the preparation of pH-responsive lipid membranes is repor... more ABSTRACT A robust and simple method for the preparation of pH-responsive lipid membranes is reported. Polymeric cushions to support a lipid bilayer were obtained by performing layer-by-layer deposition of a polycation (polyethylene imine [PEI]) and a polyanion (polystyrene sulfonate [PSS]) on quartz, with PEI as a capping layer. Subsequently, a model membrane was obtained by depositing a DPPE bilayer using Langmuir–Blodgett and Langmuir–Schäfer technique. Structural characterization using Neutron Reflectivity revealed that the separation distance between the polymeric cushion and the DPPE bilayer can be reversibly adjusted by varying the pH of the aqueous environment. These observations were further supported by Electrochemical Impedance Spectroscopy measurements. Molecular dynamics simulations suggest that coulombic forces play a key role in affecting the separation distances between the polymeric support and the lipid bilayer. Similar pH-dependent behavior was also recorded for a DPPC bilayer. We believe that this novel system offers great potential for fundamental biophysical studies of membrane properties decoupled from the underlying solid support.
Birth defects research. Part A, Clinical and molecular teratology, 2007
Background-Formation of the mammalian orofacial region involves multiple signaling pathways regul... more Background-Formation of the mammalian orofacial region involves multiple signaling pathways regulating sequential expression of and interaction between molecular signals during embryogenesis. The present study examined the expression patterns of members of the MAPK family in developing murine orofacial tissue.
The Medical journal of Australia
Birth defects research. Part A, Clinical and molecular teratology, 2010
Background-Arsenic is a ubiquitous element that is a potential carcinogen and teratogen and can c... more Background-Arsenic is a ubiquitous element that is a potential carcinogen and teratogen and can cause adverse developmental outcomes. Arsenic exerts its toxic effects through the generation of reactive oxygen species (ROS) that include hydrogen peroxide (H 2 O 2 ), superoxide-derived hydroxyl ion, and peroxyl radicals. However, the molecular mechanisms by which arsenic induces cytotoxicity in murine embryonic maxillary mesenchymal (MEMM) cells are undefined.
Indian Journal of Pharmacology
Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who developed ... more Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who developed a pleural effusion 2 months after starting antitubercular treatment for spinal tuberculosis. Isoniazid was found to be the culprit and its discontinuation caused subsidence of the effusion.
Pharmaceutical research, 2011
RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (si... more RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has the potential to selectively inhibit gene expression by degrading or blocking the translation of the target mRNA. However, delivering these RNAs to specific cells presents a significant challenge. Some of these challenges result from the necessity of traversing the circulatory system while avoiding kidney filtration, degradation by endonucleases, aggregation with serum proteins, and uptake by phagocytes. Further, non-specific delivery may result in side-effects, including the activation of immune response. We discuss the challenges in the systemic delivery to target cells, cellular uptake, endosomal release and intracellular transport of RNAi drugs and recent progress in overcoming these barriers. We also discuss approaches that increase the specificity and metabolic stability and reduce the off-target effects of RNAi strategy.
Chinese medical journal
Laboratory investigation of the patient revealed the haemoglobin of 112 g/L and blood sugar (fast... more Laboratory investigation of the patient revealed the haemoglobin of 112 g/L and blood sugar (fasting) 5.3 mmol/L. Culture of the sputum showed only commensals. Sputum for acid fast bacilli was negative in 3 consecutive early morning samples. Test for HIV was negative. Chest X-...
Pediatric dermatology
Nevus spilus, also known as speckled lentiginous nevus, is a nevoid disorder characterized by hyp... more Nevus spilus, also known as speckled lentiginous nevus, is a nevoid disorder characterized by hyperpigmented macules or papules scattered over a background of tan pigmentation. Although nevus spilus is mainly of cosmetic concern, malignant melanoma may rarely develop in the lesions. Although classically not mentioned as a hairy nevus, a few reports in literature mention overlying hypertrichosis in lesions of nevus spilus. We hereby report four cases of nevus spilus without malignant change with overlying terminal hairs that arose mainly from the background pigmented area.
The Journal of the Association of Physicians of India
PloS one, 2012
Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treat... more Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treatment drugs like paclitaxel (PTX) ineffective. The present study aims to determine the role of miRNAs and Hedgehog (Hh) pathway in chemoresistant prostate cancer and to evaluate the combination therapy using Hh inhibitor cyclopamine (CYA). Studies were conducted on PTX resistant DU145-TXR and PC3-TXR cell lines and clinical prostate tissues. Drug sensitivity and apoptosis assays showed significantly improved cytotoxicity with combination of PTX and CYA. To distinguish the presence of cancer stem cell like side populations (SP), Hoechst 33342 flow cytometry method was used. PTX resistant DU145 and PC3 cells, as well as human prostate cancer tissue possess a distinct SP fraction. Nearly 75% of the SP cells are in the G0/G1 phase compared to 62% for non-SP cells and have higher expression of stem cell markers as well. SP cell fraction was increased following PTX monotherapy and treatment with CYA or CYA plus PTX effectively reduced their numbers suggesting the effectiveness of combination therapy. SP fraction cells were allowed to differentiate and reanalyzed by Hoechst staining and gene expression analysis. Post differentiation, SP cells constitute 15.8% of total viable cells which decreases to 0.6% on treatment with CYA. The expression levels of P-gp efflux protein were also significantly decreased on treatment with PTX and CYA combination. MicroRNA profiling of DU145-TXR and PC3-TXR cells and prostate cancer tissue from the patients showed decreased expression of tumor suppressor miRNAs such as miR34a and miR200c. Treatment with PTX and CYA combination restored the expression of miR200c and 34a, confirming their role in modulating chemoresistance. We have shown that supplementing mitotic stabilizer drugs such as PTX with Hh-inhibitor CYA can reverse PTX chemoresistance and eliminate SP fraction in androgen independent, metastatic prostate cancer cell lines.
Biosensors & bioelectronics, Jan 15, 2010
Luminescent microspheres encapsulating glucose oxidase have recently been reported as potential i... more Luminescent microspheres encapsulating glucose oxidase have recently been reported as potential implantable sensors, but the operational lifetime of these systems has been limited by enzyme degradation. We report here that the longevity of these enzymatic microparticle-based sensors has been extended by the coimmobilization of glucose oxidase (GOx) and catalase (CAT) into the sensor matrix. A mathematical model was used to compare the response and longevity of the sensors with and without catalase. To experimentally test the longevity, sensors were continuously operated under normoglycemic dermal substrate concentrations and physiological conditions (5.5 mM glucose and 140 M O 2 , 37 • C and pH 7.4). The sensors incorporating CAT were experimentally shown to be ∼5 times more stable than those without CAT; nevertheless, the response of sensors with CAT still changed by approximately 20%, when operated continuously for 7 days. The experimentally determined trends obtained for the variation in sensor response due to enzyme deactivation were in close agreement with modeling predictions, which also revealed a significant apparent loss in enzyme activity upon immobilization. It was further predicted via modeling that by incorporating 0.1 mM each of active GOx and CAT, the sensors will exhibit less than 2% variation in response over 1 month of continuous operation.
Considerable progress has been made in face recognition research over the last decade especially ... more Considerable progress has been made in face recognition research over the last decade especially with the development of powerful models of face appearance (i.e., eigenfaces). Despite the variety of approaches and tools studied, however, face recognition is not accurate or robust enough to be deployed in uncontrolled environments. Recently, a number of studies have shown that infrared (IR) imagery offers a promising alternative to visible imagery due to its relative insensitive to illumination changes. However, IR has other limitations including that it is opaque to glass. As a result, IR imagery is very sensitive to facial occlusion caused by eyeglasses. In this paper, we propose fusing IR with visible images, exploiting the relatively lower sensitivity of visible imagery to occlusions caused by eyeglasses. Two different fusion schemes have been investigated in this study: (1) imagebased fusion performed in the wavelet domain and, (2) feature-based fusion performed in the eigenspace domain. In both cases, we employ Genetic Algorithms (GAs) to find an optimum strategy to perform the fusion. To evaluate and compare the proposed fusion schemes, we have performed extensive recognition experiments using the Equinox face dataset and the popular method of eigenfaces. Our results show substantial improvements in recognition performance overall, suggesting that the idea of fusing IR with visible images for face recognition deserves further consideration.
Controlling cell growth on different surfaces is crucial for many applications. For instance afte... more Controlling cell growth on different surfaces is crucial for many applications. For instance after surgery, unspecific adhesion on exogenous materials can lead to fouling that may result in infections. On the other hand, fast attachment of tissue cells is pivotal for the healing process. Hence, specific regulation of cell adhesion to substrates is a significant task especially in the biomedical
Langmuir : the ACS journal of surfaces and colloids, Jan 25, 2015
The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyeth... more The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyethylenimine (PEI) and polystyrenesulfonate (PSS) films deposited on a single crystal quartz substrate. LbL-deposited nanofilms were investigated by neutron reflectomery (NR) in contact with water in the static and fluid shear stress conditions. The fluid shear stress was applied through a laminar flow of the liquid parallel to the quartz/polymer interface in a custom-built solid-liquid interface cell. The scattering length density profiles obtained from NR results of these polyelectrolyte multilayers (PEM), measured under different shear conditions, showed proportional decrease of volume fraction of water hydrating the polymers. For the highest shear rate applied (ca. 6800 s(-1)) the water volume fraction decreased by approximately 7%. The decrease of the volume fraction of water was homogeneous through the thickness of the film. Since there were not any significant changes in the total polymer thickness, it resulted in negative osmotic pressures in the film. The PEM films were compared with the behavior of thin films of thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) deposited via spin-coating. The PEM and pNIPAM differ in their interactions with water molecules, and they showed opposite behaviors under the fluid shear stress. In both cases the polymer hydration was reversible upon the restoration of static conditions. A theoretical explanation is given to explain this difference in the effect of shear on hydration of polymeric thin films.
Pharmaceutical powder engineering often involves forming interfaces between the drug and a suitab... more Pharmaceutical powder engineering often involves forming interfaces between the drug and a suitable polymer. The structure at the interface plays a critical role in the properties and performance of the composite. However, interface structures have not been well understood due to a lack of suitable characterization tool. In this work, we have used ellipsometry and neutron reflectometry to characterize the structure of such interfaces in detail. Ellipsometry provided a quick estimate of the number of layers and their thicknesses, whereas neutron reflectometry provided richer structural information such as density, thickness, roughness, and intermixing of different layers. The combined information allowed us to develop an accurate model about the layered structure and provided information about intermixing of different layer components. Systematic use of these characterization techniques on several model systems suggests that the nature of the polymer had a small effect on the interfacial structure, while the solvent used in polymer coating had a large effect. These results provide useful information on the efforts of engineering particle properties through the control of the interfacial chemistry.
Journal of biomedicine & biotechnology, 2005
During the early stages of embryogenesis, pluripotent neural crest cells (NCC) are known to migra... more During the early stages of embryogenesis, pluripotent neural crest cells (NCC) are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR). The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.
ABSTRACT A robust and simple method for the preparation of pH-responsive lipid membranes is repor... more ABSTRACT A robust and simple method for the preparation of pH-responsive lipid membranes is reported. Polymeric cushions to support a lipid bilayer were obtained by performing layer-by-layer deposition of a polycation (polyethylene imine [PEI]) and a polyanion (polystyrene sulfonate [PSS]) on quartz, with PEI as a capping layer. Subsequently, a model membrane was obtained by depositing a DPPE bilayer using Langmuir–Blodgett and Langmuir–Schäfer technique. Structural characterization using Neutron Reflectivity revealed that the separation distance between the polymeric cushion and the DPPE bilayer can be reversibly adjusted by varying the pH of the aqueous environment. These observations were further supported by Electrochemical Impedance Spectroscopy measurements. Molecular dynamics simulations suggest that coulombic forces play a key role in affecting the separation distances between the polymeric support and the lipid bilayer. Similar pH-dependent behavior was also recorded for a DPPC bilayer. We believe that this novel system offers great potential for fundamental biophysical studies of membrane properties decoupled from the underlying solid support.
Birth defects research. Part A, Clinical and molecular teratology, 2007
Background-Formation of the mammalian orofacial region involves multiple signaling pathways regul... more Background-Formation of the mammalian orofacial region involves multiple signaling pathways regulating sequential expression of and interaction between molecular signals during embryogenesis. The present study examined the expression patterns of members of the MAPK family in developing murine orofacial tissue.
The Medical journal of Australia
Birth defects research. Part A, Clinical and molecular teratology, 2010
Background-Arsenic is a ubiquitous element that is a potential carcinogen and teratogen and can c... more Background-Arsenic is a ubiquitous element that is a potential carcinogen and teratogen and can cause adverse developmental outcomes. Arsenic exerts its toxic effects through the generation of reactive oxygen species (ROS) that include hydrogen peroxide (H 2 O 2 ), superoxide-derived hydroxyl ion, and peroxyl radicals. However, the molecular mechanisms by which arsenic induces cytotoxicity in murine embryonic maxillary mesenchymal (MEMM) cells are undefined.
Indian Journal of Pharmacology
Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who developed ... more Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who developed a pleural effusion 2 months after starting antitubercular treatment for spinal tuberculosis. Isoniazid was found to be the culprit and its discontinuation caused subsidence of the effusion.
Pharmaceutical research, 2011
RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (si... more RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). As this is a highly specific technique, efforts have been made to utilize RNAi towards potential knock down of disease-causing genes in a targeted fashion. RNAi has the potential to selectively inhibit gene expression by degrading or blocking the translation of the target mRNA. However, delivering these RNAs to specific cells presents a significant challenge. Some of these challenges result from the necessity of traversing the circulatory system while avoiding kidney filtration, degradation by endonucleases, aggregation with serum proteins, and uptake by phagocytes. Further, non-specific delivery may result in side-effects, including the activation of immune response. We discuss the challenges in the systemic delivery to target cells, cellular uptake, endosomal release and intracellular transport of RNAi drugs and recent progress in overcoming these barriers. We also discuss approaches that increase the specificity and metabolic stability and reduce the off-target effects of RNAi strategy.
Chinese medical journal
Laboratory investigation of the patient revealed the haemoglobin of 112 g/L and blood sugar (fast... more Laboratory investigation of the patient revealed the haemoglobin of 112 g/L and blood sugar (fasting) 5.3 mmol/L. Culture of the sputum showed only commensals. Sputum for acid fast bacilli was negative in 3 consecutive early morning samples. Test for HIV was negative. Chest X-...
Pediatric dermatology
Nevus spilus, also known as speckled lentiginous nevus, is a nevoid disorder characterized by hyp... more Nevus spilus, also known as speckled lentiginous nevus, is a nevoid disorder characterized by hyperpigmented macules or papules scattered over a background of tan pigmentation. Although nevus spilus is mainly of cosmetic concern, malignant melanoma may rarely develop in the lesions. Although classically not mentioned as a hairy nevus, a few reports in literature mention overlying hypertrichosis in lesions of nevus spilus. We hereby report four cases of nevus spilus without malignant change with overlying terminal hairs that arose mainly from the background pigmented area.
The Journal of the Association of Physicians of India
PloS one, 2012
Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treat... more Many prostate cancers relapse due to the generation of chemoresistance rendering first-line treatment drugs like paclitaxel (PTX) ineffective. The present study aims to determine the role of miRNAs and Hedgehog (Hh) pathway in chemoresistant prostate cancer and to evaluate the combination therapy using Hh inhibitor cyclopamine (CYA). Studies were conducted on PTX resistant DU145-TXR and PC3-TXR cell lines and clinical prostate tissues. Drug sensitivity and apoptosis assays showed significantly improved cytotoxicity with combination of PTX and CYA. To distinguish the presence of cancer stem cell like side populations (SP), Hoechst 33342 flow cytometry method was used. PTX resistant DU145 and PC3 cells, as well as human prostate cancer tissue possess a distinct SP fraction. Nearly 75% of the SP cells are in the G0/G1 phase compared to 62% for non-SP cells and have higher expression of stem cell markers as well. SP cell fraction was increased following PTX monotherapy and treatment with CYA or CYA plus PTX effectively reduced their numbers suggesting the effectiveness of combination therapy. SP fraction cells were allowed to differentiate and reanalyzed by Hoechst staining and gene expression analysis. Post differentiation, SP cells constitute 15.8% of total viable cells which decreases to 0.6% on treatment with CYA. The expression levels of P-gp efflux protein were also significantly decreased on treatment with PTX and CYA combination. MicroRNA profiling of DU145-TXR and PC3-TXR cells and prostate cancer tissue from the patients showed decreased expression of tumor suppressor miRNAs such as miR34a and miR200c. Treatment with PTX and CYA combination restored the expression of miR200c and 34a, confirming their role in modulating chemoresistance. We have shown that supplementing mitotic stabilizer drugs such as PTX with Hh-inhibitor CYA can reverse PTX chemoresistance and eliminate SP fraction in androgen independent, metastatic prostate cancer cell lines.