Smit Shah - Academia.edu (original) (raw)

Papers by Smit Shah

Research paper thumbnail of Libguides Veterinary Medicine Library Guide Home

Research paper thumbnail of Una Generalizzazione Della Funzione Speciale DI Maliuzhinets Per La Soluzione DI Problemi DI Diffrazione Da Spigoli in Superfici DI Impedenza Anisotrope

ATTI DELLA FONDAZIONE GIORGIO RONCHI, 2001

Research paper thumbnail of Cementless Highly Porous Titanium Tibial Base Plate in Total Knee Arthroplasty – Midterm Outcomes

Reconstructive Review, 2021

Introduction & Aims TKA in more active and young patients has prompted the interest in more durab... more Introduction & Aims TKA in more active and young patients has prompted the interest in more durable and biological methods of Osteo-integration with cementless components. With the emergence of improved biomaterials like porous titanium and the success, search for a cementless TKA with long-term durability and survivorship may have ended. This is a retrospective study of 492 consecutive TKAs using Cementless tibial fixation, reporting on the early 4 years clinical and radiological outcomes. Method We studied 492 TKAs performed consecutively by a single surgeon between 1stJan. 2010 and 31stDec. 2015 using a cementless, fixed bearing tibial tray (porous–Regenerex, Vanguard, Zimmer-Biomet) and a cementless femoral component (Vanguard) with no exclusion criteria. Clinical and radiological follow-up was done on these patients and in addition a comprehensive joint registry review was performed on the whole cohort (Level II evidence). Results The average Knee Society Score at final follow...

Research paper thumbnail of изменчивость массы 1 000 зёрен гороха посевного в степных условиях хакасии

Федеральное государственное бюджетное образовательное учреждение высшего образования «Хакасский государственный университет им. Н. Ф. Катанова», 2016

Research paper thumbnail of Changes in Effective Component Contents of Apple Cultivars by Ripening

Research paper thumbnail of Intramuscular lipoma of thigh

Research paper thumbnail of DIPG-62. Carboplatin Synergizes with BCL-2 Inhibitor to Potentiate Killing of Dipg Cells

Research paper thumbnail of An APETALA1 ortholog affects plant architecture and seed yield component in oilseed rape (Brassica napus L.)

Research paper thumbnail of Create a Country: For Global Understanding

Gifted Child Today Magazine, 1993

Research paper thumbnail of Effectiveness of Pelvic Proprioceptive Neuromuscular Facilitation Technique on Facilitation of Trunk Movement in Hemiparetic Stroke Patients

IOSR Journal of Dental and Medical Sciences, 2013

Research paper thumbnail of Haltere Mechanics and Mechanical Logic for Micro-Electro-Mechanical Systems (MEMS) Scale Bio-inspired Navigation Sensors

Research paper thumbnail of Abstract 4716: Tumor-specific regulation of receptor tyrosine kinases by Grp94

Cancer Research, 2015

The Endoplasmic Reticulum (ER) HSP90 paralog, Glucose Regulated Protein 94 (Grp94) is a molecular... more The Endoplasmic Reticulum (ER) HSP90 paralog, Glucose Regulated Protein 94 (Grp94) is a molecular chaperone often overexpressed in tumors. Clinically, expression of Grp94 correlates with advanced stage and poor survival in a variety of cancers, and is closely linked to cancer growth and metastasis. The majority of the cancer-related studies on Grp94 have focused narrowly on the immunogenic activity of Grp94/peptide complexes and the involvement of this protein in the secretion of IGF-I and IGF-II and the regulation of Toll-like receptors and integrins. Recently however, novel mechanistic understanding emerged regarding the cancer specific roles of Grp94: the important and unexpected tumor specific translocation of Grp94 from ER to plasma membrane to regulate the altered expression and function of plasma membrane associated cancer-proteins and its role in sustaining their transforming ability. In this respect, we found that the high density HER2 formations at the plasma membrane of HER2-overexpressing breast cancer cells necessitate Grp94 (Nat Chem Biol 2013 9(11):677-84). Inhibition of Grp94 in these cells was sufficient to destabilize plasma membrane HER2, inhibit its signaling properties, target HER2 towards a degradative pathway and as a result kill the cancer cell. We here use a chemical biology approach combined with classical methods to produce preliminary evidence for an unanticipated oncogenic role for Grp94 in maintaining high density receptor tyrosine kinases (RTKs) at the plasma membrane, particularly in cancer cells where RTKs are required to channel an amplified signaling. Our data indicate that under conditions in which stress is imposed on the cell by proteome alterations (i.e. RTK overexpression), the chaperoning function of Grp94 is vital for proper functioning of RTKs. In these cells Grp94 translocates to the plasma membrane where it functions to maintain an active conformation of RTKs and to stabilize downstream signaling through the receptor. In contrast, we find no effect of Grp94 inhibition in cells with normal or physiological RTK function/expression. Our findings provide a strong rationale for the use of chemical tools in the investigation of Grp94 associated oncogenic mechanisms and support the development of Grp94 inhibitors as a novel targeted therapy for the treatment of cancers dependent on increased signaling through plasma membrane RTKs, many of which tend to have an aggressive presentation. Citation Format: Pengrong Yan, Hardik Patel, Pallav Patel, Stefan Ochiana, Weilin Sun, Smit Shah, Paola Finotti, Cynthia Leifer, Zihai Li, Daniel Gewirth, Tony Taldone, Gabriela Chiosis. Tumor-specific regulation of receptor tyrosine kinases by Grp94. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4716. doi:10.1158/1538-7445.AM2015-4716

Research paper thumbnail of Abstract 2831: Development of selective GRP94 inhibitors for the treatment of cancer

Cancer Research, 2015

Glucose Regulated Protein 94 (Grp94) is an Hsp90 paralog localized in the lumen of the endoplasmi... more Glucose Regulated Protein 94 (Grp94) is an Hsp90 paralog localized in the lumen of the endoplasmic reticulum (ER) of higher eukaryotes. While the mechanisms associated with Grp94-pathogenic expression are still actively studied, the focus thus far of most cancer related studies has been primarily on the immunogenic activity of Grp94/peptide complexes and the involvement of this protein in the secretion of IGF-I and IGF-II and the regulation of Toll-like receptors and integrins. This status quo has recently changed when work from our lab has shown that in certain breast cancers the maintenance of a high density HER2 species at the plasma membrane and its associated aberrant signaling also requires Grp94, rendering these tumors highly sensitive to Grp94 inhibition. The discovery of selective and potent Grp94 inhibitors has been hindered due to the high similarity of the ATP-binding regulatory pocket of the Hsp90 paralogs. However, recent work from our lab has shown that this apparent roadblock can be overcome by using library screening and structural and computational analysis to discover purine-based molecules that show 100-fold selectivity for the Grp94 isoform. Herein, we detail for the first time the structure activity relationship of the selective purine derived Grp94 molecules. This work provides insights on how to overcome the high structural similarity of Hsp90s in the ligand binding pocket, and also reports selective and therapeutically relevant Grp94 inhibitors based on a purine scaffold. These initial inhibitors have potent activity against cancer cells providing an important platform for the development of Grp94 inhibitors with drug-like features and potential for clinical translation. Citation Format: Stefan O. Ochiana, Tony Taldone, Hardik J. Patel, Pallav Patel, Yan Pengrong, Weilin Sun, Anna Rodina, Smit Shah, Daniel T. Gewirth, Gabriela Chiosis. Development of selective GRP94 inhibitors for the treatment of cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2831. doi:10.1158/1538-7445.AM2015-2831

Research paper thumbnail of Clinicopathologic implications of NF1 gene alterations in diffuse gliomas

Human Pathology, 2015

Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1) i... more Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1) in a subset of glioblastoma (GBM), usually associated with the mesenchymal molecular subtype. To understand the significance of NF1 genetic alterations in diffuse gliomas in general, we evaluated public databases and tested for NF1 copy number alterations in a cohort using fluorescence in situ hybridization. NF1 genetic loss (homozygous NF1 deletions or mutations with predicted functional consequences) was present in 30 (of 281) (11%) GBM and 21 (of 286) (7%) lower-grade gliomas in The Cancer Genome Atlas data. Furthermore, NF1 loss was associated with worse overall and disease-specific survival in the lower-grade glioma, but not GBM, Group in The Cancer Genome Atlas cohort. IDH1 or 2 mutations co-existed in lower-grade gliomas with NF1 loss (36%) but not in GBM. In our cohort studied by fluorescence in situ hybridization, NF1/17q (n = 2) or whole Ch17 (n = 3) losses were only identified in the GBM group (5/86 [6%]). Tumors with NF1/Ch17 loss were predominantly adult GBM (4/5); lacked EGFR amplification (0/4), strong p53 immunolabeling (1/5), or IDH1 (R132H) protein expression (0/5); but expressed the mesenchymal marker podoplanin in 4/5. NF1 genetic loss occurs in a subset of diffuse gliomas, and its significance deserves further exploration.

Research paper thumbnail of Application of random and regular input in analytical separation methods: A critical insight

Chemometrics and Intelligent Laboratory Systems, 2005

Research paper thumbnail of Modelling Building Shadows on Rooftop Generating 3D City Model

International Journal for Research in Applied Science and Engineering Technology, 2021

Research paper thumbnail of Consequence of Source Ripple Factor in Conducted Voltage Emission Measurement

Huge dv/dt and di/dt due to high switching frequency and ripples present in AC-DC converter infal... more Huge dv/dt and di/dt due to high switching frequency and ripples present in AC-DC converter infallibly introduce unwanted Electromagnetic Interference (EMI) noise voltage through parasitic/distributed parameters of the DC source. In this paper, the entire test setup for conducted emission (CE) is made to measure the conducted voltage disturbance of Equipment Under Test (EUT) due to various DC sources with different percentage ripple factors used to supply. The measurement carried out in the frequency band 150kHz to 30MHz as per CISPR 11 [2]/ CISPR 22 [1]. The dominated DC source responsible for the significant conducted voltage disturbance measurement results are analyzed and to mitigate the conducted emission manoeuvring based on DC source is proposed. Practical measurement are used to validate the mitigation method.

Research paper thumbnail of Frailty Status Is a More Robust Predictor Than Age of Spinal Tumor Surgery Outcomes: A NSQIP Analysis of 4,662 Patients

Research paper thumbnail of Additional file 6: of An APETALA1 ortholog affects plant architecture and seed yield component in oilseed rape (Brassica napus L.)

Figure S3. Phylogenetic tree of AP1 protein sequences from different Brassicaceae species. The tr... more Figure S3. Phylogenetic tree of AP1 protein sequences from different Brassicaceae species. The tree was constructed using the Neighbour-Joining method. The default bootstrap value was set to 100. The numbers on branches represent bootstrap values in percentage. (PPTX 245 kb)

Research paper thumbnail of RESEARCH ARTICLE OPEN ACCESS Characterization and Corrosion Study of Titanium Anodized Film Developed in KOH Bath

Anodizing is an electrolytic passivation process used to increase the thickness of the natural ox... more Anodizing is an electrolytic passivation process used to increase the thickness of the natural oxide layer on the surface of metal parts. Aluminum is ideally suited to anodizing, although other nonferrous metals, such as tantalum and titanium, can also be anodized. Titanium is used as a biocompatible material in human implants due to its excellent corrosion and wears resistance. Stable, continuous, highly adherent, and protective oxide films can be developed on titanium using various acid or alkaline baths. Anodizing of titanium generates a spectrum of different color without use of dyes. This spectrum of color dependent on the thickness of the oxide, interference of light reflecting off the oxide surface and reflecting off the underlying metal surface. The anodized film of Titanium is mainly consists of TiO2 or mixtures of TiO2 & Ti2O3 etc. In the present work, Pure Titanium plate has been anodized using bath of KOH at different voltage ranges. The anodized film is characterized by...

Research paper thumbnail of Libguides Veterinary Medicine Library Guide Home

Research paper thumbnail of Una Generalizzazione Della Funzione Speciale DI Maliuzhinets Per La Soluzione DI Problemi DI Diffrazione Da Spigoli in Superfici DI Impedenza Anisotrope

ATTI DELLA FONDAZIONE GIORGIO RONCHI, 2001

Research paper thumbnail of Cementless Highly Porous Titanium Tibial Base Plate in Total Knee Arthroplasty – Midterm Outcomes

Reconstructive Review, 2021

Introduction & Aims TKA in more active and young patients has prompted the interest in more durab... more Introduction & Aims TKA in more active and young patients has prompted the interest in more durable and biological methods of Osteo-integration with cementless components. With the emergence of improved biomaterials like porous titanium and the success, search for a cementless TKA with long-term durability and survivorship may have ended. This is a retrospective study of 492 consecutive TKAs using Cementless tibial fixation, reporting on the early 4 years clinical and radiological outcomes. Method We studied 492 TKAs performed consecutively by a single surgeon between 1stJan. 2010 and 31stDec. 2015 using a cementless, fixed bearing tibial tray (porous–Regenerex, Vanguard, Zimmer-Biomet) and a cementless femoral component (Vanguard) with no exclusion criteria. Clinical and radiological follow-up was done on these patients and in addition a comprehensive joint registry review was performed on the whole cohort (Level II evidence). Results The average Knee Society Score at final follow...

Research paper thumbnail of изменчивость массы 1 000 зёрен гороха посевного в степных условиях хакасии

Федеральное государственное бюджетное образовательное учреждение высшего образования «Хакасский государственный университет им. Н. Ф. Катанова», 2016

Research paper thumbnail of Changes in Effective Component Contents of Apple Cultivars by Ripening

Research paper thumbnail of Intramuscular lipoma of thigh

Research paper thumbnail of DIPG-62. Carboplatin Synergizes with BCL-2 Inhibitor to Potentiate Killing of Dipg Cells

Research paper thumbnail of An APETALA1 ortholog affects plant architecture and seed yield component in oilseed rape (Brassica napus L.)

Research paper thumbnail of Create a Country: For Global Understanding

Gifted Child Today Magazine, 1993

Research paper thumbnail of Effectiveness of Pelvic Proprioceptive Neuromuscular Facilitation Technique on Facilitation of Trunk Movement in Hemiparetic Stroke Patients

IOSR Journal of Dental and Medical Sciences, 2013

Research paper thumbnail of Haltere Mechanics and Mechanical Logic for Micro-Electro-Mechanical Systems (MEMS) Scale Bio-inspired Navigation Sensors

Research paper thumbnail of Abstract 4716: Tumor-specific regulation of receptor tyrosine kinases by Grp94

Cancer Research, 2015

The Endoplasmic Reticulum (ER) HSP90 paralog, Glucose Regulated Protein 94 (Grp94) is a molecular... more The Endoplasmic Reticulum (ER) HSP90 paralog, Glucose Regulated Protein 94 (Grp94) is a molecular chaperone often overexpressed in tumors. Clinically, expression of Grp94 correlates with advanced stage and poor survival in a variety of cancers, and is closely linked to cancer growth and metastasis. The majority of the cancer-related studies on Grp94 have focused narrowly on the immunogenic activity of Grp94/peptide complexes and the involvement of this protein in the secretion of IGF-I and IGF-II and the regulation of Toll-like receptors and integrins. Recently however, novel mechanistic understanding emerged regarding the cancer specific roles of Grp94: the important and unexpected tumor specific translocation of Grp94 from ER to plasma membrane to regulate the altered expression and function of plasma membrane associated cancer-proteins and its role in sustaining their transforming ability. In this respect, we found that the high density HER2 formations at the plasma membrane of HER2-overexpressing breast cancer cells necessitate Grp94 (Nat Chem Biol 2013 9(11):677-84). Inhibition of Grp94 in these cells was sufficient to destabilize plasma membrane HER2, inhibit its signaling properties, target HER2 towards a degradative pathway and as a result kill the cancer cell. We here use a chemical biology approach combined with classical methods to produce preliminary evidence for an unanticipated oncogenic role for Grp94 in maintaining high density receptor tyrosine kinases (RTKs) at the plasma membrane, particularly in cancer cells where RTKs are required to channel an amplified signaling. Our data indicate that under conditions in which stress is imposed on the cell by proteome alterations (i.e. RTK overexpression), the chaperoning function of Grp94 is vital for proper functioning of RTKs. In these cells Grp94 translocates to the plasma membrane where it functions to maintain an active conformation of RTKs and to stabilize downstream signaling through the receptor. In contrast, we find no effect of Grp94 inhibition in cells with normal or physiological RTK function/expression. Our findings provide a strong rationale for the use of chemical tools in the investigation of Grp94 associated oncogenic mechanisms and support the development of Grp94 inhibitors as a novel targeted therapy for the treatment of cancers dependent on increased signaling through plasma membrane RTKs, many of which tend to have an aggressive presentation. Citation Format: Pengrong Yan, Hardik Patel, Pallav Patel, Stefan Ochiana, Weilin Sun, Smit Shah, Paola Finotti, Cynthia Leifer, Zihai Li, Daniel Gewirth, Tony Taldone, Gabriela Chiosis. Tumor-specific regulation of receptor tyrosine kinases by Grp94. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4716. doi:10.1158/1538-7445.AM2015-4716

Research paper thumbnail of Abstract 2831: Development of selective GRP94 inhibitors for the treatment of cancer

Cancer Research, 2015

Glucose Regulated Protein 94 (Grp94) is an Hsp90 paralog localized in the lumen of the endoplasmi... more Glucose Regulated Protein 94 (Grp94) is an Hsp90 paralog localized in the lumen of the endoplasmic reticulum (ER) of higher eukaryotes. While the mechanisms associated with Grp94-pathogenic expression are still actively studied, the focus thus far of most cancer related studies has been primarily on the immunogenic activity of Grp94/peptide complexes and the involvement of this protein in the secretion of IGF-I and IGF-II and the regulation of Toll-like receptors and integrins. This status quo has recently changed when work from our lab has shown that in certain breast cancers the maintenance of a high density HER2 species at the plasma membrane and its associated aberrant signaling also requires Grp94, rendering these tumors highly sensitive to Grp94 inhibition. The discovery of selective and potent Grp94 inhibitors has been hindered due to the high similarity of the ATP-binding regulatory pocket of the Hsp90 paralogs. However, recent work from our lab has shown that this apparent roadblock can be overcome by using library screening and structural and computational analysis to discover purine-based molecules that show 100-fold selectivity for the Grp94 isoform. Herein, we detail for the first time the structure activity relationship of the selective purine derived Grp94 molecules. This work provides insights on how to overcome the high structural similarity of Hsp90s in the ligand binding pocket, and also reports selective and therapeutically relevant Grp94 inhibitors based on a purine scaffold. These initial inhibitors have potent activity against cancer cells providing an important platform for the development of Grp94 inhibitors with drug-like features and potential for clinical translation. Citation Format: Stefan O. Ochiana, Tony Taldone, Hardik J. Patel, Pallav Patel, Yan Pengrong, Weilin Sun, Anna Rodina, Smit Shah, Daniel T. Gewirth, Gabriela Chiosis. Development of selective GRP94 inhibitors for the treatment of cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2831. doi:10.1158/1538-7445.AM2015-2831

Research paper thumbnail of Clinicopathologic implications of NF1 gene alterations in diffuse gliomas

Human Pathology, 2015

Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1) i... more Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1) in a subset of glioblastoma (GBM), usually associated with the mesenchymal molecular subtype. To understand the significance of NF1 genetic alterations in diffuse gliomas in general, we evaluated public databases and tested for NF1 copy number alterations in a cohort using fluorescence in situ hybridization. NF1 genetic loss (homozygous NF1 deletions or mutations with predicted functional consequences) was present in 30 (of 281) (11%) GBM and 21 (of 286) (7%) lower-grade gliomas in The Cancer Genome Atlas data. Furthermore, NF1 loss was associated with worse overall and disease-specific survival in the lower-grade glioma, but not GBM, Group in The Cancer Genome Atlas cohort. IDH1 or 2 mutations co-existed in lower-grade gliomas with NF1 loss (36%) but not in GBM. In our cohort studied by fluorescence in situ hybridization, NF1/17q (n = 2) or whole Ch17 (n = 3) losses were only identified in the GBM group (5/86 [6%]). Tumors with NF1/Ch17 loss were predominantly adult GBM (4/5); lacked EGFR amplification (0/4), strong p53 immunolabeling (1/5), or IDH1 (R132H) protein expression (0/5); but expressed the mesenchymal marker podoplanin in 4/5. NF1 genetic loss occurs in a subset of diffuse gliomas, and its significance deserves further exploration.

Research paper thumbnail of Application of random and regular input in analytical separation methods: A critical insight

Chemometrics and Intelligent Laboratory Systems, 2005

Research paper thumbnail of Modelling Building Shadows on Rooftop Generating 3D City Model

International Journal for Research in Applied Science and Engineering Technology, 2021

Research paper thumbnail of Consequence of Source Ripple Factor in Conducted Voltage Emission Measurement

Huge dv/dt and di/dt due to high switching frequency and ripples present in AC-DC converter infal... more Huge dv/dt and di/dt due to high switching frequency and ripples present in AC-DC converter infallibly introduce unwanted Electromagnetic Interference (EMI) noise voltage through parasitic/distributed parameters of the DC source. In this paper, the entire test setup for conducted emission (CE) is made to measure the conducted voltage disturbance of Equipment Under Test (EUT) due to various DC sources with different percentage ripple factors used to supply. The measurement carried out in the frequency band 150kHz to 30MHz as per CISPR 11 [2]/ CISPR 22 [1]. The dominated DC source responsible for the significant conducted voltage disturbance measurement results are analyzed and to mitigate the conducted emission manoeuvring based on DC source is proposed. Practical measurement are used to validate the mitigation method.

Research paper thumbnail of Frailty Status Is a More Robust Predictor Than Age of Spinal Tumor Surgery Outcomes: A NSQIP Analysis of 4,662 Patients

Research paper thumbnail of Additional file 6: of An APETALA1 ortholog affects plant architecture and seed yield component in oilseed rape (Brassica napus L.)

Figure S3. Phylogenetic tree of AP1 protein sequences from different Brassicaceae species. The tr... more Figure S3. Phylogenetic tree of AP1 protein sequences from different Brassicaceae species. The tree was constructed using the Neighbour-Joining method. The default bootstrap value was set to 100. The numbers on branches represent bootstrap values in percentage. (PPTX 245 kb)

Research paper thumbnail of RESEARCH ARTICLE OPEN ACCESS Characterization and Corrosion Study of Titanium Anodized Film Developed in KOH Bath

Anodizing is an electrolytic passivation process used to increase the thickness of the natural ox... more Anodizing is an electrolytic passivation process used to increase the thickness of the natural oxide layer on the surface of metal parts. Aluminum is ideally suited to anodizing, although other nonferrous metals, such as tantalum and titanium, can also be anodized. Titanium is used as a biocompatible material in human implants due to its excellent corrosion and wears resistance. Stable, continuous, highly adherent, and protective oxide films can be developed on titanium using various acid or alkaline baths. Anodizing of titanium generates a spectrum of different color without use of dyes. This spectrum of color dependent on the thickness of the oxide, interference of light reflecting off the oxide surface and reflecting off the underlying metal surface. The anodized film of Titanium is mainly consists of TiO2 or mixtures of TiO2 & Ti2O3 etc. In the present work, Pure Titanium plate has been anodized using bath of KOH at different voltage ranges. The anodized film is characterized by...