Browsing by Subject "pancreatic cancer"
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Item BEST PRACTICES FOR PANCREATIC MASSES OF UNKNOWN ETIOLOGY(2013-04-12) Bachman, RyanPurpose: A 76 year-old Caucasian male presented with painless jaundice which progressively worsened over one week. The only other complaints the patient stated was an unexplained 10 pound weight loss in the past 2 months and mild fatigue for 1 day. His past medical history was significant for non-small cell lung cancer status post left lower lobe lung resection 8 months ago, hyperlipidemia, COPD, and a past smoking history of 260 pack years. After his lung resection, he had a follow up PET scan that showed a possible nonspecific gallbladder lesion which had never been fully worked up. Methods: Evaluation of the patients mass was performed with an ultrasound of the abdomen that showed a dilated common bile and intra hepatic duct dilation with no stones. A subsequent CT of his abdomen showed a 4cm pancreatic mass with a 1.1cm pancreatic duct dilation. ERCP was attempted for brushings of cells and a stent placement was attempted but was unsuccessful for both. Further workup of his mass with an endoscopic ultrasound and biopsy of the pancreas revealed adenocarcinoma. Results: The differential diagnosis for this patients jaundice was choledocholithiasis versus pancreatic mass that was possibly a metastatic spread from his primary lung cancer several months prior. The ultrasound revealed no stones, which helped rule out the choledocholithiasis. However, the ERCP was attempted and unsuccessful which led to a delay in his definitive diagnosis, as well as the inability to place a stent to relieve his original complaint of jaundice. Conclusions: The evaluation of a patient when pancreatic cancer is suspected should start with a CT scan with IV contrast. This method has a high level of sensitivity for mass and allows for assessment for possible surgical resection of the mass. This patient's PET scan was never worked up by his original physician, which may have led to a delay of his diagnosis which could potentially lead to a less favorable outcome. There is currently no recommended screening method for pancreatic cancer. This leads to only 20% of pancreatic cancers diagnosed when they are localized and potentially cured by surgical resection. Once pancreatic cancer has advanced locally and invaded local vasculature or metastasized it is no longer curative with surgery and there are no set guidelines for treatment.Item Copper Tolfenamic Acid as a Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cell Growth via Downregulating Sp1 and Sp3 Transcription Factors(2018-08) Hurtado, Myrna L.; Basu, Alakananda; Lacko, Andras G.; Mathew, Porunelloor A.; Cheng, Yi-Qiang; Ma, RongDespite medical advancements, PaCa unfortunately still remains a lethal malignancy. Patients are typically diagnosed once the cancer is advanced and metastatic, making them ineligible for surgery. This cancer is usually aggressive at the time of diagnosis, so chemo and radiation offer little benefit. Therefore, PaCa urgently requires more effective and sensitizing agents for treatment. Two targets of interest for PaCa have been transcription factors Sp1 and Sp3. Both Sp1 and Sp3 are involved with regulating cell proliferation, differentiation and apoptosis. Their overexpression has been found to contribute to the progression, advancement, and poor prognosis of many types of cancers, including pancreatic. Survivin, an inhibitor of apoptosis protein, is a gene known to be regulated by both these Sp proteins. Survivin has also been found to be overexpressed in various tumor types and adds to the cancer's resistance to cytotoxic therapies. For these reasons, Sp1, Sp3, and survivin have been targets of interest for PaCa and researchers have becoming interested in finding drugs that inhibit their expression. Tolfenamic Acid (TA) is a generic migraine medicine sold in Europe. The small molecule TA has been gaining popularity for its anti-cancer properties such as inhibition of cell growth and induction of apoptosis in various tumor models. TA has been shown to work by downregulation of Sp proteins and survivin. TA has also been demonstrated to sensitize PaCa cells to radiation treatment. Although the results seen with TA thus far seem promising, its IC50 value is slightly high. Recently, it has been suggested that a copper(II) complex of TA (Cu-TA) can produce a higher therapeutic response; however, its efficacy has yet to be tested in gastro-intestinal cancers. Here, we used human PaCa cell lines (MIA PaCa-2 and Panc1) to evaluate the therapeutic efficacy of Cu-TA in an effort to increase TA's efficacy. This project contains three specific aims. Aim 1: Characterization of Cu-TA and determining its stability and anti-proliferative activity in human pancreatic cancer cell lines. Aim 2: Evaluate the effect of Cu- TA on potential markers associated with PaCa cell growth. Aim 3: Use gene expression analysis to precisely elucidate the underlying mechanisms of Cu-TA's anticancer activity in PaCa cells. Cu-TA was found to have an anti-proliferative effect in PaCa cells and its IC50 value was half that of TA's. Characterization of Cu-TA demonstrated its stability as a compound and its biological stability. Importantly, treatment of Cu-TA on cardiomyocytes did not affect cell viability. This is significant since NSAIDs can potentially cause cardiotoxicity. Cu-TA also downregulates expression of Sp proteins and survivin, molecular markers involved with PaCa growth and progression. Additionally, Cu-TA induces apoptosis and cell cycle arrest in PaCa. Finally, RNA sequencing and subsequent pathway analysis of treatment revealed Cu-TA affects pathways involved with cancer progression and metastasis. Thus, these results demonstrate Cu-TA as a potential anti-cancer agent for PaCa.Item Development and In Vitro Characterization of Gemcitabine Loaded Nanoparticles for Pancreatic Cancer Therapy(2021-05) Pham, Jennifer H.; Ranjan, Amalendu P.; Fudala, Rafal; Mathew, Stephen O.Pancreatic Ductal Adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths worldwide and the most common type of pancreatic malignancy (90%). With a poor five-year survival rate of only 5-8%, complete surgical resection remains the only curative treatment. However, most patients are diagnosed at a later stage where chemotherapy and radiotherapy are the only options. Gemcitabine is the FDA-approved treatment for PDAC, but the current therapy leads to more severe side effects due to the instability of gemcitabine in the blood stream and its poor membrane permeability. Nanoparticles are effective in cancer therapy because they allow modifications that make for a more effective delivery method and also reduces the toxicity to normal tissue. In this proposed study, we aim to formulate, optimize and evaluate the in vitro effectiveness of gemcitabine loaded nanoparticles in a PDAC cell line in order to improve the effectiveness of current chemotherapy treatments for pancreatic ductal adenocarcinoma. We found out of the three types of nanoplatforms used for encapsulating gemcitabine (GEM-NPs): polymeric, liposomal and lipid polymer hybrid, the liposomal nanoparticles were the most effective in the encapsulation of gemcitabine according to the physicochemical properties, such as average particle size, zeta potential, drug loading and encapsulation efficiency. In vitro functional evaluation of liposomal formulation was done in a PDAC cell line (PANC-1). This study suggests that the use of liposomal nanoparticles is the most beneficial in the encapsulation and delivery of gemcitabine.