Pancreatic cancer (PanCa) is a highly lethal disease with a poor 5 year survival rate, less than 7%. It has a dismal prognosis, and more than 50% of cases are detected at an advanced and metastatic stage. Gemcitabine (GEM) is a gold standard chemotherapy used for PanCa treatment. However, GEM-acquired resistance in cancer cells is considered as a major setback for its continued clinical implementation. This phenomenon is evidently linked to de novo lipid synthesis. PanCa cells rely on de novo lipid synthesis, which is a prime event in survival and one of the key drivers for tumorigenesis, cancer progression, and drug resistance. Thus, the depletion of lipogenesis or lipid metabolism can not only improve treatment outcomes but also overcome chemoresistance, which is an unmet clinical need. Toward this effort, our study reports a unique paclitaxel-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PPNPs) formulation which can target lipid metabolism and improve anticancer efficacy of GEM in PanCa cells. PPNPs inhibit excessive lipid formation and alter membrane stability with compromised membrane integrity, which was confirmed by Fourier transform infrared and zeta potential measurements. The effective interference of PPNPs in lipid metabolic signaling was determined by reduction in the expression of FASN, ACC, lipin, and Cox-2 proteins. This molecular action profoundly enhances efficacy of GEM as evident through enhanced inhibitory effects on the tumorigenic and metastasis assays in PanCa cells. These data clearly suggest that the ablation of lipid metabolism might offer an innovative approach for the improved therapeutic outcome in PanCa patients.
: Cancer cells undergo metabolic reprogramming to support cell proliferation, growth, and dissemination. Alterations in lipid metabolism, and specifically the uptake and synthesis of fatty acids (FAs), comprise one well-documented aspect of this reprogramming. Recent studies have revealed an expanded range of roles played by FA in promoting the aggressiveness of cancer while simultaneously identifying new potential targets for cancer therapy. This article provides a brief review of these advance...
Abstract Pancreatic cancer (PanCa) is a major cause of cancer-related death due to limited therapeutic options. As pancreatic tumors are highly desmoplastic, they prevent appropriate uptake of therapeutic payloads. Thus, our objective is to develop a next-generation nanoparticle system for treating PanCa. We generated a multi-layered Pluronic F127 and polyvinyl alcohol stabilized and poly-L-lysine coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs). This formu...
Last. Xuqi Li(Xi'an Jiaotong University)H-Index: 26
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Background Diabetes is recognized to be a risk factor of pancreatic cancer, but the mechanism has not been fully elucidated. Sterol regulatory element binding protein 1 (SREBP1) is an important transcription factor involved in both lipid metabolism and tumor progression. However, the relationship between high glucose microenvironment, SREBP1 and pancreatic cancer remains to be explored.
#1Sheema Khan(UTHSC: University of Tennessee Health Science Center)H-Index: 23
#2Saini Setua(UTHSC: University of Tennessee Health Science Center)H-Index: 7
Last. Subhash C. Chauhan(UTHSC: University of Tennessee Health Science Center)H-Index: 49
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Abstract Pancreatic cancer is a complex disease accounting for fibrotic tumors and an aggressive phenotype. Gemcitabine (GEM) is used as a standard therapy, which develops chemoresistance leading to poor patient outcome. We have recently developed a superparamagnetic iron oxide nanoparticle (SPION) formulation of curcumin (SP-CUR), which is a nontoxic, bioactive anti-inflammatory/anti-cancer agent for its enhanced delivery in tumors. In this study, we demonstrate that SP-CUR effectively delivers...
Introduction: Despite clinical efforts, pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The scarcity of effective therapies can be reflected by the lack of reliable biomarkers to adapt anticancer drugs prescription to tumors’ and patients’ features. Areas covered: Pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best matches individual and tumor genetic profile, but it has not yet led to gains in outcome. This review describe...
#1Pallabita Chowdhury(UTHSC: University of Tennessee Health Science Center)H-Index: 12
#2Prashanth K.B. Nagesh(UTHSC: University of Tennessee Health Science Center)H-Index: 10
Last. Murali M. Yallapu(UTHSC: University of Tennessee Health Science Center)H-Index: 34
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Abstract Paclitaxel (PTX) is a gold standard chemotherapeutic agent for breast, ovarian, pancreatic and non-small cell lung carcinoma. However, in clinical use PTX can have adverse side effects or inadequate pharmacodynamic parameters, limiting its use. Nanotechnology is often employed to reduce the therapeutic dosage required for effective therapy, while also minimizing the systemic side effects of chemotherapy drugs. However, there is no nanoformulation of paclitaxel with chemosensitization mo...
#1Vivek K. Kashyap(UTHSC: University of Tennessee Health Science Center)H-Index: 8
#2Qinghui Wang(UTHSC: University of Tennessee Health Science Center)H-Index: 9
Last. Subhash C. Chauhan(UTHSC: University of Tennessee Health Science Center)H-Index: 49
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The management of pancreatic cancer (PanCa) is exceptionally difficult due to poor response to available therapeutic modalities. Tubulins play a major role in cell dynamics, thus are important molecular targets for cancer therapy. Among various tubulins, βIII and βIV-tubulin isoforms have been primarily implicated in PanCa progression, metastasis and chemo-resistance. However, specific inhibitors of these isoforms that have potent anti-cancer activity with low toxicity are not readily available....
A hallmark of prostate cancer progression is dysregulation of lipid metabolism via overexpression of fatty acid synthase (FASN), a key enzyme in de novo fatty acid synthesis. Metastatic castration-resistant prostate cancer (mCRPC) develops resistance to inhibitors of androgen receptor (AR) signaling through a variety of mechanisms, including the emergence of the constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective FASN inhib...
Last. Ahmedin Jemal(ACS: American Cancer Society)H-Index: 139
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: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the Nati...
Nanomedicines can be used for a variety of cancer therapies including tumor-targeted drug delivery, hyperthermia, and photodynamic therapy. Poly (lactic-co-glycolic acid) (PLGA)-based materials are frequently used in such setups. This review article gives an overview of the properties of previously reported PLGA nanoparticles (NPs), their behavior in biological systems, and their use for cancer therapy. Strategies are emphasized to target PLGA NPs to the tumor site passively and actively. Furthe...
Upper gastrointestinal (GI) carcinomas are characterized as one of the deadliest cancer types with the highest recurrence rates. Their treatment is challenging due to late diagnosis, early metastasis formation, resistance to systemic therapy and complicated surgeries performed in poorly accessible locations. Current cancer medication face deficiencies such as high toxicity and systemic side-effects due to the non-specific distribution of the drug agent. Nanomedicine has the potential to offer so...