Manpreet Sambi - Academia.edu (original) (raw)

Papers by Manpreet Sambi

The therapeutic potential of polymeric nanoparticles has garnered attention due to the multiple a... more The therapeutic potential of polymeric nanoparticles has garnered attention due to the multiple applications for which this technology can be used. This is particularly important for cancer as many of the cytotoxic drugs that are used to treat patients have negative side effects on healthy cells. Polymeric nanoparticle technology can reduce these negative side effects as they can be engineered to respond to the unique external environment surrounding tumors (i.e. an acidic environment and pH response) or they can target specific receptors such as folate, found exclusively on cancer cells and release their payload directly. This review will discuss the current applications of polymer nanoparticles in nanomedicine as a whole, with a focus on the development of polymeric nanoparticles and their applications as targeted drug delivery vehicles.

The gastrointestinal (GI) tract is colonized by trillions of microorganisms that play a vital rol... more The gastrointestinal (GI) tract is colonized by trillions of microorganisms that play a vital role in maintaining homeostasis, contributing to several local and systemic processes including digestion, and have been shown to influence the immune response. Although the crucial contributions of the gut microbiota have been studied in great detail in relation to normal GI function, recent studies have exposed a previously unknown link between commensal bacteria, cancer progression, and treatment efficacy. Preliminary studies have shown that an imbalance in gut microbiota may influence cancer progression in part due to the development of an inflammatory environment that potentiates cancer progression and the possibility of driver and passenger microorganisms that induce DNA damage. Furthermore, in relation to the efficacy of immunotherapies, several microorganisms are involved in enhancing the anti-tumor response by helping to activate tumor antigen specific T-cells. However, this particular area of research is in its infancy and requires additional studies to further understand the implications of the link between commensal bacteria and cancer progression.

Elevated cell surface sialic acid expression levels on colorectal cancer cells has been associate... more Elevated cell surface sialic acid expression levels on colorectal cancer cells has been associated with increased metastatic burden. Sialic acid expression influences cancer cell-cell adhesion, cell-extracellular matrix adhesion, as well as emboli formation, apoptosis and cell growth. All of these processes are associated with the metastatic cascade, ultimately resulting in the formation of successful metastatic foci. Here we briefly summarize the steps involved in the metastatic cascade, and outline the regulatory effects of sialic acid expression on the progression of metastasis as they apply to colorectal cancer. Lastly, we discuss current models available to study these interactions as they relate to metastasis.

Gastrointestinal (GI) cancer is an all-encompassing term that refers to the forms of cancers of t... more Gastrointestinal (GI) cancer is an all-encompassing term that refers to the forms of cancers of the digestive system including the esophagus, liver, gallbladder, stomach, small intestine, colon, rectum, anus and pancreas. Of the cancers mentioned, pancreatic ductal adenocarcinoma (PDAC) is the most deadly form of GI cancer owing partially to the late detection of this malignancy. At this point of diagnosis, the disease has metastasized and very few treatment options are available to patients. The aggressive nature of this cancer can be attributed to the substantial number of mutations acquired during its progression and its subsequent resistance to standard therapies such as chemotherapy and radiation. The heterogeneity of the subpopulations that are chemoresistant, particularly the tumor initiating population as known as cancer stem cells, make administrating conventional first-line treatments such as gemcitabine more difficult. Lastly, the tumor microenvironment and the early establishment of a metastatic niche by exosomes that facilitate dissemination of cancer cells to distant organs also contribute to the incurability of this type of cancer. Here we discuss the current clinical challenges in treating PDAC and the possible avenues that should be explored in order to improve current treatment options available to patients.

One of the primary challenges in developing effective therapies for malignant tumors is the speci... more One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The
cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively,
these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For
example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have
briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current
understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research,
including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current advancements in the development of multitarget therapeutics that have
shown promising results in clinical and preclinical studies when used alone or in combination with traditional regimens of surgery, chemotherapy, and/or radiation.

Translational Cancer Research

Breast Cancer: Targets and Therapy, 2017

One of the primary challenges in developing effective therapies for malignant tumors is the speci... more One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research, including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current advancements in the development of multitarget therapeutics that have shown promising results in clinical and preclinical studies when used alone or in combination with traditional regimens of surgery, chemotherapy, and/or radiation.

Stem cell reviews, Jan 27, 2017

The development of strategies for tissue regeneration and bio-artificial organ development is bas... more The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix. While artificial three-dimensional scaffolds are available, using the natural extracellular matrix scaffold is advantageous because it has a distinct architecture that is difficult to replicate. The adult extracellular matrix is predicted to mediate signaling related to tissue repair not embryogenesis but existing similarities between the two argues that the extracellular matrix will influence the differentiation of stem and progenitor cells. Previous studies using undiffe...

Stem cell reports, Jan 4, 2015

Efficient differentiation of pluripotent cells to proximal and distal lung epithelial cell popula... more Efficient differentiation of pluripotent cells to proximal and distal lung epithelial cell populations remains a challenging task. The 3D extracellular matrix (ECM) scaffold is a key component that regulates the interaction of secreted factors with cells during development by often binding to and limiting their diffusion within local gradients. Here we examined the role of the lung ECM in differentiation of pluripotent cells in vitro and demonstrate the robust inductive capacity of the native lung matrix alone. Extended culture of stem cell-derived definitive endoderm on decellularized lung scaffolds in defined, serum-free medium resulted in differentiation into mature airway epithelia, complete with ciliated cells, club cells, and basal cells with morphological and functional similarities to native airways. Heparitinase I, but not chondroitinase ABC, treatment of scaffolds revealed that the differentiation achieved is dependent on heparan sulfate proteoglycans and its bound factors...

Today, emerging therapies must effectively shut down multiple enabling characteristics that drive... more Today, emerging therapies must effectively shut down multiple enabling characteristics that drive pancreatic cancer invasion and progression. These therapies include the concomitant suppression of growth factor signaling and anti-apoptotic pathways, immune-derived promoters of tumorigenesis, mechanisms of acquired drug resistance, as well as pro-metastatic signals that facilitate cancer cell
migration and successful homing of disseminated tumor cells. Here, we provide an overview of some of the current treatment options available for patients with pancreatic cancer, as well as their limitations. Finally, we review some alternative multi-target strategies that may provide increased
efficacy in cancer therapy.

Translational Cancer Research

Breast Cancer: Targets and Therapy, 2017

One of the primary challenges in developing effective therapies for malignant tumors is the speci... more One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research, including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current advancements in the development of multitarget therapeutics that have shown promising results in clinical and preclinical studies when used alone or in combination with traditional regimens of surgery, chemotherapy, and/or radiation.

Stem cell reviews, Jan 27, 2017

Stem cell reports, Jan 4, 2015