Zhiming Mai - Academia.edu (original) (raw)

Papers by Zhiming Mai

Research paper thumbnail of Experimental Lymphatic Filariasis in Gerbils (Meriones Unguiculatus): Molecular Cloning and Expression of Gerbil Cytokines and Measurement of Cytokine Gene Expression During a Primary Infection of Brugia Pahangi

xii CHAPTER ONE: INTRODUCTION 1 1.1 An Overview of the Dissertation 1 1.2 Cytokines 1 1.3 Lymphat... more xii CHAPTER ONE: INTRODUCTION 1 1.1 An Overview of the Dissertation 1 1.2 Cytokines 1 1.3 Lymphatic Filariasis 7 1.4 The Role of Cytokines in Immune Responses to Nematode Parasites 11 1.5 Hypothesis and Objects 14 CHAPTER TWO: CROSS-SPECIES PCR CLONING OF GERBIL (MERIONES UNGUICULATUS) INTERLEUKIN-2 cDNA AND ITS EXPRESSION IN COS-7 CELLS 17 2.

Research paper thumbnail of Supplement: Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

Research paper thumbnail of Spatiotemporal synchronized cancer combination therapy

Research paper thumbnail of Optical probes for molecular-guided surgery: Using photomedicine to prevent recurrence in the surgical bed (Conference Presentation)

Molecular-Guided Surgery: Molecules, Devices, and Applications II, 2016

Research paper thumbnail of Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016

Research paper thumbnail of Predicting photodynamic therapy efficacy with photoacoustic imaging (Conference Presentation)

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016

Research paper thumbnail of Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer (Conference Presentation)

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016

Research paper thumbnail of Nanotechnology-based combination therapy improves treatment response in cancer models

Proceedings of Spie the International Society For Optical Engineering, Jun 1, 2009

Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynam... more Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies. Here, we investigate the effect of neutralizing VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. In vitro, nanocells containing Avastin (NCA) significantly enhanced cytotoxicity in PanCa cells. NCA based PDT also significantly improved treatment response in mice that were orthotopically implanted with PanCa. Avastin delivered extracellularly in combination with PDT did not show any improvement. Here we propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Research paper thumbnail of Photodynamic therapy synergizes with irinotecan to overcome compensatory mechanisms and improve treatment outcomes in pancreatic cancer

Cancer research, Jan 30, 2015

The ability of tumor cells to adapt to therapeutic regimens by activating alternative survival an... more The ability of tumor cells to adapt to therapeutic regimens by activating alternative survival and growth pathways remains a major challenge in cancer therapy. Therefore, the most effective treatments will involve interactive strategies that target multiple non-overlapping pathways while eliciting synergistic outcomes and minimizing systemic toxicities. Nanoliposomal irinotecan is FDA-approved for gemcitabine-refractory metastatic pancreatic cancer (PanCa). However, the full potential of irinotecan treatment is hindered by several cancer cell survival mechanisms, including ATP-binding cassette G2 (ABCG2) transporter-mediated irinotecan efflux from cells. Here we demonstrate that benzoporphyrin derivative (BPD)-based photodynamic therapy (PDT), a photochemical cytotoxic modality that activates the apoptotic pathway, reduced ABCG2 expression to increase intracellular irinotecan levels in PanCa. Moreover, we show that PDT inhibited survivin expression. While PDT potentiated irinotecan ...

Research paper thumbnail of A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

Nature nanotechnology, Jan 18, 2016

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumou... more Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)-a multikinase inhibitor-encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses ...

Research paper thumbnail of Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer

Nanomedicine: Nanotechnology, Biology and Medicine, 2015

A lack of intracellular delivery systems has limited the use of biologics such as monoclonal anti... more A lack of intracellular delivery systems has limited the use of biologics such as monoclonal antibodies (mAb) that abrogate molecular signaling pathways activated to promote escape from cancer treatment. We hypothesized that intracellular co-delivery of the photocytotoxic chromophore benzoporphyrin derivative monoacid A (BPD) and the anti-VEGF mAb bevacizumab in a nanophotoactivatable liposome (nanoPAL) might enhance the efficacy of photodynamic therapy (PDT) combined with suppression of VEGF-mediated signaling pathways. As a proof-of-concept we found that nanoPAL-PDT induced enhanced extra- and intracellular bevacizumab delivery and enhanced acute cytotoxicity in vitro. In an in vivo subcutaneous mouse model of pancreatic ductal adenocarcinoma, nanoPAL-PDT achieved significantly enhanced tumor reduction. We attribute this to the optimal incorporation of insoluble BPD into the lipid bilayer, enhancing photocytotoxicity, and the simultaneous spatiotemporal delivery of bevacizumab, ensuring efficient neutralization of the rapid but transient burst of VEGF following PDT.

Research paper thumbnail of 335533 Nanoparticle-Assisted, Mechanism-Based Combination Photodynamic and Irinotecan Therapy for Pancreatic Cancer

The purpose of this study is to strategically combine two clinical-relevant, nanotechnology-based... more The purpose of this study is to strategically combine two clinical-relevant, nanotechnology-based therapies to facilitate rapid clinical translation and immediately improve on the dismal statistics of pancreatic cancer (PanCa) patients. We hypothesized that benzoporphyrin derivative (BPD)-based photodynamic therapy (PDT) (Phase I/II study, solid PanCa) destroys tumor efflux transporters, which may help maintain high intracellular concentrations of Irinotecan (CPT-11) (Phase III study, metastatic PanCa) to reduce tumor burden and prolong survival. We test our hypothesis in orthotopic PanCa models. Two types of liposomes were fabricated by adapting procedures from literature. They are: (i) Liposome with BPD in lipid bilayer (LBPD) and (ii) Liposome encapsulating CPT-11 in aqueous core (LCPT-11). Lipids (DPPC, DOTAP, Cholesterol, DSPE-mPEG at a molar ratio of 2:0.2:1.0:0.2) were mixed in chloroform (for LBPD, dissolve with 0.2 mM BPD), and the chloroform was evaporated. Lipid films wer...

Research paper thumbnail of In vivo evaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints

Journal of Biomedical Optics, 2015

In view of the increase in cancer-related mortality rates in low- to middle-income countries (LMI... more In view of the increase in cancer-related mortality rates in low- to middle-income countries (LMIC), there is an urgent need to develop economical therapies that can be utilized at minimal infrastructure institutions. Photodynamic therapy (PDT), a photochemistry-based treatment modality, offers such a possibility provided that low-cost light sources and photosensitizers are available. In this proof-of-principle study, we focus on adapting the PDT light source to a low-resource setting and compare an inexpensive, portable, battery-powered light-emitting diode (LED) light source with a standard, high-cost laser source. The comparison studies were performed in vivo in a xenograft murine model of human squamous cell carcinoma subjected to 5-aminolevulinic acid-induced protoporphyrin IX PDT. We observed virtually identical control of the tumor burden by both the LED source and the standard laser source. Further insights into the biological response were evaluated by biomarker analysis of necrosis, microvessel density, and hypoxia [carbonic anhydrase IX (CAIX) expression] among groups of control, LED-PDT, and laser-PDT treated mice. There is no significant difference in the percent necrotic volume and CAIX expression in tumors that were treated with the two different light sources. These encouraging preliminary results merit further investigations in orthotopic animal models of cancers prevalent in LMICs.

Research paper thumbnail of Chitinase secretion by encysting Entamoeba invadens and transfected Entamoeba histolytica trophozoites: localization of secretory vesicles, endoplasmic reticulum, and Golgi apparatus

Infection and immunity, 1999

Entamoeba histolytica, the protozoan parasite that phagocytoses bacteria and host cells, has a ve... more Entamoeba histolytica, the protozoan parasite that phagocytoses bacteria and host cells, has a vesicle/vacuole-filled cytosol like that of macrophages. In contrast, the infectious cyst form has four nuclei and a chitin wall. Here, anti-chitinase antibodies identified hundreds of small secretory vesicles in encysting E. invadens parasites and in E. histolytica trophozoites overexpressing chitinase under an actin gene promoter. Abundant small secretory vesicles were also identified with antibodies to the surface antigen Ariel and with a fluorescent substrate of cysteine proteinases. Removal of an N-terminal signal sequence directed chitinase to the cytosol. Addition of a C-terminal KDEL peptide, identified on amebic BiP, retained chitinase in a putative endoplasmic reticulum, which was composed of a few vesicles of mixed sizes. A putative Golgi apparatus, which was Brefeldin A sensitive and composed of a few large, perinuclear vesicles, was identified with antibodies to ADP-ribosylati...

Research paper thumbnail of Hsp60 is targeted to a cryptic mitochondrion-derived organelle ("crypton") in the microaerophilic protozoan parasite Entamoeba histolytica

Molecular and cellular biology, 1999

Entamoeba histolytica is a microaerophilic protozoan parasite in which neither mitochondria nor m... more Entamoeba histolytica is a microaerophilic protozoan parasite in which neither mitochondria nor mitochondrion-derived organelles have been previously observed. Recently, a segment of an E. histolytica gene was identified that encoded a protein similar to the mitochondrial 60-kDa heat shock protein (Hsp60 or chaperonin 60), which refolds nuclear-encoded proteins after passage through organellar membranes. The possible function and localization of the amebic Hsp60 were explored here. Like Hsp60 of mitochondria, amebic Hsp60 RNA and protein were both strongly induced by incubating parasites at 42 degreesC. 5' and 3' rapid amplifications of cDNA ends were used to obtain the entire E. histolytica hsp60 coding region, which predicted a 536-amino-acid Hsp60. The E. histolytica hsp60 gene protected from heat shock Escherichia coli groEL mutants, demonstrating the chaperonin function of the amebic Hsp60. The E. histolytica Hsp60, which lacked characteristic carboxy-terminal Gly-Met r...

Research paper thumbnail of <title>Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer</title>

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX, 2010

ABSTRACT Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to t... more ABSTRACT Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the &quot;right place at the right time&quot;. This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called &quot;nanocells&quot; in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Research paper thumbnail of Abstract B148: Ultrasound image guided combination therapies involving photodynamic therapy and irinotecan

Molecular Cancer Therapeutics, 2013

Research paper thumbnail of Abstract A2: Targeting intracellular VEGF using nanotechnology for subcellular delivery of bevacizumab improves efficacy of combination therapy against pancreatic cancer

Molecular Cancer Therapeutics, 2009

Research paper thumbnail of <title>Nanotechnology-based combination therapy improves treatment response in cancer models</title>

Photodynamic Therapy: Back to the Future, 2009

Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynam... more Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs

Research paper thumbnail of <title>Analytic modeling of antibody versus nanocell delivery of photosensitizer</title>

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX, 2010

Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this ca... more Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this can be distilled down into parameters which allow computational modeling. In this paper, the basic rate equations and diffusion kernel for the time and space modeling of delivery are developed, along with an analytical solution to this equation. The model is then used to compare

Research paper thumbnail of Experimental Lymphatic Filariasis in Gerbils (Meriones Unguiculatus): Molecular Cloning and Expression of Gerbil Cytokines and Measurement of Cytokine Gene Expression During a Primary Infection of Brugia Pahangi

xii CHAPTER ONE: INTRODUCTION 1 1.1 An Overview of the Dissertation 1 1.2 Cytokines 1 1.3 Lymphat... more xii CHAPTER ONE: INTRODUCTION 1 1.1 An Overview of the Dissertation 1 1.2 Cytokines 1 1.3 Lymphatic Filariasis 7 1.4 The Role of Cytokines in Immune Responses to Nematode Parasites 11 1.5 Hypothesis and Objects 14 CHAPTER TWO: CROSS-SPECIES PCR CLONING OF GERBIL (MERIONES UNGUICULATUS) INTERLEUKIN-2 cDNA AND ITS EXPRESSION IN COS-7 CELLS 17 2.

Research paper thumbnail of Supplement: Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

Research paper thumbnail of Spatiotemporal synchronized cancer combination therapy

Research paper thumbnail of Optical probes for molecular-guided surgery: Using photomedicine to prevent recurrence in the surgical bed (Conference Presentation)

Molecular-Guided Surgery: Molecules, Devices, and Applications II, 2016

Research paper thumbnail of Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016

Research paper thumbnail of Predicting photodynamic therapy efficacy with photoacoustic imaging (Conference Presentation)

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016

Research paper thumbnail of Mechanistic exploration of a bi-directional PDT-based combination in pancreatic cancer (Conference Presentation)

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016

Research paper thumbnail of Nanotechnology-based combination therapy improves treatment response in cancer models

Proceedings of Spie the International Society For Optical Engineering, Jun 1, 2009

Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynam... more Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies. Here, we investigate the effect of neutralizing VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. In vitro, nanocells containing Avastin (NCA) significantly enhanced cytotoxicity in PanCa cells. NCA based PDT also significantly improved treatment response in mice that were orthotopically implanted with PanCa. Avastin delivered extracellularly in combination with PDT did not show any improvement. Here we propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Research paper thumbnail of Photodynamic therapy synergizes with irinotecan to overcome compensatory mechanisms and improve treatment outcomes in pancreatic cancer

Cancer research, Jan 30, 2015

The ability of tumor cells to adapt to therapeutic regimens by activating alternative survival an... more The ability of tumor cells to adapt to therapeutic regimens by activating alternative survival and growth pathways remains a major challenge in cancer therapy. Therefore, the most effective treatments will involve interactive strategies that target multiple non-overlapping pathways while eliciting synergistic outcomes and minimizing systemic toxicities. Nanoliposomal irinotecan is FDA-approved for gemcitabine-refractory metastatic pancreatic cancer (PanCa). However, the full potential of irinotecan treatment is hindered by several cancer cell survival mechanisms, including ATP-binding cassette G2 (ABCG2) transporter-mediated irinotecan efflux from cells. Here we demonstrate that benzoporphyrin derivative (BPD)-based photodynamic therapy (PDT), a photochemical cytotoxic modality that activates the apoptotic pathway, reduced ABCG2 expression to increase intracellular irinotecan levels in PanCa. Moreover, we show that PDT inhibited survivin expression. While PDT potentiated irinotecan ...

Research paper thumbnail of A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

Nature nanotechnology, Jan 18, 2016

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumou... more Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)-a multikinase inhibitor-encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses ...

Research paper thumbnail of Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer

Nanomedicine: Nanotechnology, Biology and Medicine, 2015

A lack of intracellular delivery systems has limited the use of biologics such as monoclonal anti... more A lack of intracellular delivery systems has limited the use of biologics such as monoclonal antibodies (mAb) that abrogate molecular signaling pathways activated to promote escape from cancer treatment. We hypothesized that intracellular co-delivery of the photocytotoxic chromophore benzoporphyrin derivative monoacid A (BPD) and the anti-VEGF mAb bevacizumab in a nanophotoactivatable liposome (nanoPAL) might enhance the efficacy of photodynamic therapy (PDT) combined with suppression of VEGF-mediated signaling pathways. As a proof-of-concept we found that nanoPAL-PDT induced enhanced extra- and intracellular bevacizumab delivery and enhanced acute cytotoxicity in vitro. In an in vivo subcutaneous mouse model of pancreatic ductal adenocarcinoma, nanoPAL-PDT achieved significantly enhanced tumor reduction. We attribute this to the optimal incorporation of insoluble BPD into the lipid bilayer, enhancing photocytotoxicity, and the simultaneous spatiotemporal delivery of bevacizumab, ensuring efficient neutralization of the rapid but transient burst of VEGF following PDT.

Research paper thumbnail of 335533 Nanoparticle-Assisted, Mechanism-Based Combination Photodynamic and Irinotecan Therapy for Pancreatic Cancer

The purpose of this study is to strategically combine two clinical-relevant, nanotechnology-based... more The purpose of this study is to strategically combine two clinical-relevant, nanotechnology-based therapies to facilitate rapid clinical translation and immediately improve on the dismal statistics of pancreatic cancer (PanCa) patients. We hypothesized that benzoporphyrin derivative (BPD)-based photodynamic therapy (PDT) (Phase I/II study, solid PanCa) destroys tumor efflux transporters, which may help maintain high intracellular concentrations of Irinotecan (CPT-11) (Phase III study, metastatic PanCa) to reduce tumor burden and prolong survival. We test our hypothesis in orthotopic PanCa models. Two types of liposomes were fabricated by adapting procedures from literature. They are: (i) Liposome with BPD in lipid bilayer (LBPD) and (ii) Liposome encapsulating CPT-11 in aqueous core (LCPT-11). Lipids (DPPC, DOTAP, Cholesterol, DSPE-mPEG at a molar ratio of 2:0.2:1.0:0.2) were mixed in chloroform (for LBPD, dissolve with 0.2 mM BPD), and the chloroform was evaporated. Lipid films wer...

Research paper thumbnail of In vivo evaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints

Journal of Biomedical Optics, 2015

In view of the increase in cancer-related mortality rates in low- to middle-income countries (LMI... more In view of the increase in cancer-related mortality rates in low- to middle-income countries (LMIC), there is an urgent need to develop economical therapies that can be utilized at minimal infrastructure institutions. Photodynamic therapy (PDT), a photochemistry-based treatment modality, offers such a possibility provided that low-cost light sources and photosensitizers are available. In this proof-of-principle study, we focus on adapting the PDT light source to a low-resource setting and compare an inexpensive, portable, battery-powered light-emitting diode (LED) light source with a standard, high-cost laser source. The comparison studies were performed in vivo in a xenograft murine model of human squamous cell carcinoma subjected to 5-aminolevulinic acid-induced protoporphyrin IX PDT. We observed virtually identical control of the tumor burden by both the LED source and the standard laser source. Further insights into the biological response were evaluated by biomarker analysis of necrosis, microvessel density, and hypoxia [carbonic anhydrase IX (CAIX) expression] among groups of control, LED-PDT, and laser-PDT treated mice. There is no significant difference in the percent necrotic volume and CAIX expression in tumors that were treated with the two different light sources. These encouraging preliminary results merit further investigations in orthotopic animal models of cancers prevalent in LMICs.

Research paper thumbnail of Chitinase secretion by encysting Entamoeba invadens and transfected Entamoeba histolytica trophozoites: localization of secretory vesicles, endoplasmic reticulum, and Golgi apparatus

Infection and immunity, 1999

Entamoeba histolytica, the protozoan parasite that phagocytoses bacteria and host cells, has a ve... more Entamoeba histolytica, the protozoan parasite that phagocytoses bacteria and host cells, has a vesicle/vacuole-filled cytosol like that of macrophages. In contrast, the infectious cyst form has four nuclei and a chitin wall. Here, anti-chitinase antibodies identified hundreds of small secretory vesicles in encysting E. invadens parasites and in E. histolytica trophozoites overexpressing chitinase under an actin gene promoter. Abundant small secretory vesicles were also identified with antibodies to the surface antigen Ariel and with a fluorescent substrate of cysteine proteinases. Removal of an N-terminal signal sequence directed chitinase to the cytosol. Addition of a C-terminal KDEL peptide, identified on amebic BiP, retained chitinase in a putative endoplasmic reticulum, which was composed of a few vesicles of mixed sizes. A putative Golgi apparatus, which was Brefeldin A sensitive and composed of a few large, perinuclear vesicles, was identified with antibodies to ADP-ribosylati...

Research paper thumbnail of Hsp60 is targeted to a cryptic mitochondrion-derived organelle ("crypton") in the microaerophilic protozoan parasite Entamoeba histolytica

Molecular and cellular biology, 1999

Entamoeba histolytica is a microaerophilic protozoan parasite in which neither mitochondria nor m... more Entamoeba histolytica is a microaerophilic protozoan parasite in which neither mitochondria nor mitochondrion-derived organelles have been previously observed. Recently, a segment of an E. histolytica gene was identified that encoded a protein similar to the mitochondrial 60-kDa heat shock protein (Hsp60 or chaperonin 60), which refolds nuclear-encoded proteins after passage through organellar membranes. The possible function and localization of the amebic Hsp60 were explored here. Like Hsp60 of mitochondria, amebic Hsp60 RNA and protein were both strongly induced by incubating parasites at 42 degreesC. 5' and 3' rapid amplifications of cDNA ends were used to obtain the entire E. histolytica hsp60 coding region, which predicted a 536-amino-acid Hsp60. The E. histolytica hsp60 gene protected from heat shock Escherichia coli groEL mutants, demonstrating the chaperonin function of the amebic Hsp60. The E. histolytica Hsp60, which lacked characteristic carboxy-terminal Gly-Met r...

Research paper thumbnail of <title>Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer</title>

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX, 2010

ABSTRACT Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to t... more ABSTRACT Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the &quot;right place at the right time&quot;. This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called &quot;nanocells&quot; in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Research paper thumbnail of Abstract B148: Ultrasound image guided combination therapies involving photodynamic therapy and irinotecan

Molecular Cancer Therapeutics, 2013

Research paper thumbnail of Abstract A2: Targeting intracellular VEGF using nanotechnology for subcellular delivery of bevacizumab improves efficacy of combination therapy against pancreatic cancer

Molecular Cancer Therapeutics, 2009

Research paper thumbnail of <title>Nanotechnology-based combination therapy improves treatment response in cancer models</title>

Photodynamic Therapy: Back to the Future, 2009

Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynam... more Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs

Research paper thumbnail of <title>Analytic modeling of antibody versus nanocell delivery of photosensitizer</title>

Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX, 2010

Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this ca... more Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this can be distilled down into parameters which allow computational modeling. In this paper, the basic rate equations and diffusion kernel for the time and space modeling of delivery are developed, along with an analytical solution to this equation. The model is then used to compare