Shreyas Gaikwad - Academia.edu (original) (raw)
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Papers by Shreyas Gaikwad
Cancer Research
Pediatric glioblastoma multiforme (GBM) is considered to be the second most lethal childhood canc... more Pediatric glioblastoma multiforme (GBM) is considered to be the second most lethal childhood cancer type after leukemia. Recent preclinical, clinical and genomic studies have highlighted upon the role of Hippo-Yap pathway in the progression of pediatric GBM. In addition, recent studies have established the role of YAP in creating immune suppressive tumor microenvironment (TME) facilitating drug resistance, recurrence and metastasis of GBM tumors. Herein, we report that ‘moxidectin’ an anti-helminthic drug inhibits the proliferation of SF268, SF295, SF188 and CT-2A Luc GBM cells by inducing apoptosis. Immunoblotting and immunofluorescence microscopy studies show that moxidectin mediates its effects by inhibiting MEK-ERK pathway, a regulator of Hippo-YAP signaling. As a result, moxidectin suppressed the nuclear translocation and transcriptional activity of YAP/TAZ-TEAD complex. Oral administration of 3.5mg/kg moxidectin suppressed the growth of GBM tumors by 90% in intracranial tumor ...
Cancer Research
Medulloblastoma (MB) is one of the most frequently occurring malignant brain tumors in children, ... more Medulloblastoma (MB) is one of the most frequently occurring malignant brain tumors in children, which accounts for 20% of all pediatric brain tumors and 40% of posterior fossa tumors. Despite advancements in the understanding of MB pathogenesis and identification of novel therapeutic targets, MB has emerged to be one of the most lethal pediatric diseases with peak incidences occurring in children aged between 5 and 7 years old. Numerous factors have been identified to hamper the management of several brain tumors including MB. However, the presence of medulloblastoma stem cells (MBSCs) and impermeability of drugs to cross the blood brain barrier (BBB) are identified as the major obstacles in MB management. MB is highly enriched with MBSCs, a subpopulation of MB cells that imparts therapy resistant, invasive and recurrent characteristics to MB. In our study, we evaluated the effects of Pimavanserin (PVT) in MB. Our results demonstrated that PVT treatment suppressed the proliferation...
Almost every corner of the world is under surveillance. However, crimes (anomalies) can occur any... more Almost every corner of the world is under surveillance. However, crimes (anomalies) can occur anywhere and anytime. Duration of anomalous activities is for a very short time as compared to normal activities. Advancements in computer vision have proved Convolutional Neural Networks (CNN) to be a compelling solution for anomaly detection in videos. This paper proposes to bring together different methods for effective anomaly detection. The dependency of Machine Learning on massive sets of the hand-labeled training dataset is time-consuming. To avoid this, a predictive model is constructed that learns with weak supervision using Multiple Instance Learning (MIL) approaches. The combination of motion information (optical flow) along with spatial information (RGB) obtained from 3-dimensional Convolutional Networks (C3D), using 2-stream architecture, offers a stronger visual representation of videos, thus enhancing anomaly detection performance. TVL1 is used to obtain the optical flow representation of videos. After detection, suspicious behaviors in videos are tracked on the UCF Crime dataset videos.
International Journal of Molecular Sciences
A major contributing factor in triple-negative breast cancer progression is its ability to evade ... more A major contributing factor in triple-negative breast cancer progression is its ability to evade immune surveillance. One mechanism for this immunosuppression is through ribosomal protein S19 (RPS19), which facilitates myeloid-derived suppressor cells (MDSCs) recruitment in tumors, which generate cytokines TGF-β and IL-10 and induce regulatory T cells (Tregs), all of which are immunosuppressive and enhance tumor progression. Hence, enhancing the immune system in breast tumors could be a strategy for anticancer therapeutics. The present study evaluated the immune response of atovaquone, an antiprotozoal drug, in three independent breast-tumor models. Our results demonstrated that oral administration of atovaquone reduced HCC1806, CI66 and 4T1 paclitaxel-resistant (4T1-PR) breast-tumor growth by 45%, 70% and 42%, respectively. MDSCs, TGF-β, IL-10 and Tregs of blood and tumors were analyzed from all of these in vivo models. Our results demonstrated that atovaquone treatment in mice bea...
Antioxidants
Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical ... more Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some ...
Antioxidants
Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical ... more Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some ...
Antioxidants
Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical ... more Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some ...
Cancer Research
Pediatric glioblastoma multiforme (GBM) is considered to be the second most lethal childhood canc... more Pediatric glioblastoma multiforme (GBM) is considered to be the second most lethal childhood cancer type after leukemia. Recent preclinical, clinical and genomic studies have highlighted upon the role of Hippo-Yap pathway in the progression of pediatric GBM. In addition, recent studies have established the role of YAP in creating immune suppressive tumor microenvironment (TME) facilitating drug resistance, recurrence and metastasis of GBM tumors. Herein, we report that ‘moxidectin’ an anti-helminthic drug inhibits the proliferation of SF268, SF295, SF188 and CT-2A Luc GBM cells by inducing apoptosis. Immunoblotting and immunofluorescence microscopy studies show that moxidectin mediates its effects by inhibiting MEK-ERK pathway, a regulator of Hippo-YAP signaling. As a result, moxidectin suppressed the nuclear translocation and transcriptional activity of YAP/TAZ-TEAD complex. Oral administration of 3.5mg/kg moxidectin suppressed the growth of GBM tumors by 90% in intracranial tumor ...
Cancer Research
Medulloblastoma (MB) is one of the most frequently occurring malignant brain tumors in children, ... more Medulloblastoma (MB) is one of the most frequently occurring malignant brain tumors in children, which accounts for 20% of all pediatric brain tumors and 40% of posterior fossa tumors. Despite advancements in the understanding of MB pathogenesis and identification of novel therapeutic targets, MB has emerged to be one of the most lethal pediatric diseases with peak incidences occurring in children aged between 5 and 7 years old. Numerous factors have been identified to hamper the management of several brain tumors including MB. However, the presence of medulloblastoma stem cells (MBSCs) and impermeability of drugs to cross the blood brain barrier (BBB) are identified as the major obstacles in MB management. MB is highly enriched with MBSCs, a subpopulation of MB cells that imparts therapy resistant, invasive and recurrent characteristics to MB. In our study, we evaluated the effects of Pimavanserin (PVT) in MB. Our results demonstrated that PVT treatment suppressed the proliferation...
Almost every corner of the world is under surveillance. However, crimes (anomalies) can occur any... more Almost every corner of the world is under surveillance. However, crimes (anomalies) can occur anywhere and anytime. Duration of anomalous activities is for a very short time as compared to normal activities. Advancements in computer vision have proved Convolutional Neural Networks (CNN) to be a compelling solution for anomaly detection in videos. This paper proposes to bring together different methods for effective anomaly detection. The dependency of Machine Learning on massive sets of the hand-labeled training dataset is time-consuming. To avoid this, a predictive model is constructed that learns with weak supervision using Multiple Instance Learning (MIL) approaches. The combination of motion information (optical flow) along with spatial information (RGB) obtained from 3-dimensional Convolutional Networks (C3D), using 2-stream architecture, offers a stronger visual representation of videos, thus enhancing anomaly detection performance. TVL1 is used to obtain the optical flow representation of videos. After detection, suspicious behaviors in videos are tracked on the UCF Crime dataset videos.
International Journal of Molecular Sciences
A major contributing factor in triple-negative breast cancer progression is its ability to evade ... more A major contributing factor in triple-negative breast cancer progression is its ability to evade immune surveillance. One mechanism for this immunosuppression is through ribosomal protein S19 (RPS19), which facilitates myeloid-derived suppressor cells (MDSCs) recruitment in tumors, which generate cytokines TGF-β and IL-10 and induce regulatory T cells (Tregs), all of which are immunosuppressive and enhance tumor progression. Hence, enhancing the immune system in breast tumors could be a strategy for anticancer therapeutics. The present study evaluated the immune response of atovaquone, an antiprotozoal drug, in three independent breast-tumor models. Our results demonstrated that oral administration of atovaquone reduced HCC1806, CI66 and 4T1 paclitaxel-resistant (4T1-PR) breast-tumor growth by 45%, 70% and 42%, respectively. MDSCs, TGF-β, IL-10 and Tregs of blood and tumors were analyzed from all of these in vivo models. Our results demonstrated that atovaquone treatment in mice bea...
Antioxidants
Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical ... more Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some ...
Antioxidants
Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical ... more Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some ...
Antioxidants
Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical ... more Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some ...