Cancer
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30050
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Item A rare case of nasal septum perforation in a breast cancer pt receiving Trastuzumab(2020) Mohanaselvan, ArvindselvanTrastuzumab is a monoclonal antibody that is used specifically in patients with metastatic breast cancer that is HER2 receptor positive, where it binds to the HER2 receptor and slows down cell multiplication. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that facilitates signaling pathways of cell growth, division, motility and repair. ASCO, NCCN, ESMO currently recommend the administration of trastuzumab with chemotherapy for the management of HER2-positive early-stage breast cancer in adjuvant settings.In this report we present a case of spontaneous nasal perforation in a patient who received Trastuzumab but not Bevacizumab as part of her chemotherapy. Trastuzumab is the standard of care chemotherapy in patients with HER2 positive metastatic breast cancer. A literature review of nasal septum perforation as a complication of chemotherapy in breast cancer patients showed that Bevacizumab is a drug that is known to cause the said complication. Docataxel has also been shown to cause perforation in certain patients. In our patient, therapy did involve Docataxel but it was stopped 6 months before the pt developed the perforation. At the time of symptom development pt was only on Trastuzumab. This raises the question if the HER2 receptor attacking monoclonal antibody can cause mucosal breakdown leading to complications such as this. More case reports in the future might shed light on this peculiar phenomenon and help in devising methods to tackle such side effects.Item A Rare Case of Synchronous Gallbladder Metastasis Secondary to Gastric Adenocarcinoma(2020) Jackson, Terrence; Nagatomo, Kei; Osman, Houssam; Jeyarajah, Dhiresh; Cho, Edward; Lim, JosephBackground: Gallbladder metastasis is rare and usually presents in the end stage of a malignancy. When they do occur, most of the time it is secondary to melanoma. However, there have been case reports of gallbladder metastasis secondary to gastric cancer; this has been reported in Asian countries such as Japan, South Korea, and Turkey where gastric cancer rates are higher than western countries. This is the first case of gallbladder metastasis secondary to gastric cancer in the United States to ever be reported. Case Presentation: A 67-year-old female initially developed hematemesis, and further workup showed gastric cancer with initial pathology showing T3N0M0. Clinically she was asymptomatic. Patient underwent total gastrectomy with roux-en-y esophagojejunostomy and cholecystectomy. The final pathology showed T3N2M1 gastric adenocarcinoma with metastatic adenocarcinoma of the gallbladder. Conclusion: This is a very rare case adds to the limited literature on this topic. Due to lack of level one data on gallbladder metastasis in general, case reports such as this one provides a unique and valuable insight into this pathology.Item Acute Lymphoblastic Leukemia in Adolescent & Young Adult Populations and Adherence to Protocol: A Case Study(2020) Acosta, Melissa; Bowman, William; Albritton, Karen; Brewer, ShannonAdolescent and young adult (AYA) populations treated for acute lymphoblastic leukemia (ALL) have worse outcomes compared to pediatric patients. In addition, the AYA population has an increased rate of non-adherence to treatment, particularly in the maintenance therapy phase. Case Report: The case is that of a 19 year old male who was diagnosed with Philadelphia chromosome-positive B-cell ALL. He was managed at an adult cancer center and started on the Hyper-CVAD treatment protocol plus Tyrosine Kinase Inhibitor (TKI) and achieved complete remission. All of his subsequent treatment cycles were delayed for up to fifteen days due to difficulties with compliance and timely follow-up. The patient expressed frustration with prolonged hospital stays and ultimately left the treatment center against medical advice, failing to complete the intensive protocol. Anticipating a poor prognosis for long term remission, the patient was referred for bone marrow transplant; he had variable compliance with follow-up and oral TKI. Approximately 15 months after initial diagnosis, he presented in a state of leukemic relapse. He was transferred to a pediatric leukemia center for intensive relapse therapy but died due to infectious complications. This case illustrates the unique challenges faced when treating AYA leukemia patients and that failure of compliance may adversely impact outcomes. Further research into these unique factors is warranted in order to improve protocol adherence and thereby treatment in AYA populations.Item Adolescents and Young Adults with Cancer Continue to Face Disparities in Rate of Change in Five-Year Survival(2020) Bowman, William; Rutledge, Laura; Bleyer, Archie; Ewart, MackenziePurpose: Cancer is a devastating disease process that affects the lives of millions around the world. A standard metric of progress, of particular interest within the discipline of cancer research is the measurement of therapeutic progress, which is commonly measured through analyses of 5-year survival statistics. While cancer therapies have come a long way, the adolescent and young adult (AYA) cancer patient population faces many unique obstacles such as cancer identification, proper diagnosis, adequate treatment, and continuity of care. It has been estimated that globally there are more than one million incident cases of cancer in AYAs between 15 and 39 years, and nearly 400,000 deaths due to cancer in the age group. These obstacles have led to a lack of improvement in the outcomes for AYA cancer patients of 15 to 39 years of age when compared with younger and older patient populations Methods: Large-data analysis via mathematical derivation of 5-year survival statistics from the National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) registries from 1975-2009. Results: The analysis yields a measurable disparity in the therapeutic improvement of the AYA cancer patient population when compared against the derivation of 5-year survival statistics for children and middle-aged or older adults within United States. Conclusions: Despite recent publications and analyses that state the contrary - more initiatives and research are needed to correct the lagging disparities and to improve the overall survival in the AYA population.Item ALK Variations and Targeted Therapy in Pediatric Cancers at Cook Children's Medical Center(2020) Ray, Anish; Swilling, AubreyPurpose: The goal of this project is to report the prevalence of anaplastic lymphoma kinase (ALK) variations in pediatric cancers from a single institution over a six-year period, and to describe the use of small molecules to target these genetic aberrations. Methods: A retrospective chart review was conducted on 82 patients from Cook Children's Medical Center who had tumors sequenced through Foundation Medicine, Inc. from January 1, 2013 to May 1, 2019. Remote sequencing provided results of identified genetic variants and available approved or experimental targeted therapies. In patients harboring ALK variations, the use of available targeted therapies (ALK inhibitors) was analyzed with respect to time to treatment failure (TTF), overall survival (OS), and adverse events (AEs). Results: Of the 82 patients in the study, seven were found to harbor ALK variations, and six patients elected to receive targeted therapy. In three patients, sustained clinical benefit from ALK inhibitors was observed. One patient with relapsed neuroblastoma received crizotinib for 3.9 years. Two other patients, one with refractory neuroblastoma and the other treatment-naïve leiomyosarcoma, were still continued on lorlatinib and crizotinib, each totaling a respective 2.8 years and 217 ongoing days on therapy. None of these patients reported AEs attributed to the targeted therapy, and all three patients were survived at the time of data collection. Conclusion: In certain refractory or relapsed pediatric neoplasms, therapy options remain limited. This study illustrates the use of genomic sequencing to identify ALK as an actionable variant with potential clinical utility.Item Anti-proliferative activity of clotam and copper-clotam against T-cell Acute lymphoblastic leukemia cell line CCRF-CEM(2020) Basha, Riyaz; Siraj, Sohail; Sankpal, Umesh; Polu, Rujula; Patel, KrishnaPurpose: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children younger than 5 years. Patients with ALL have bone marrow that produces immature white blood cells, which are unable to effectively fight infections. NSAIDs are common pain reliving agents that act through COX inhibition, which stops the production of prostaglandins. Clotam (Tolfenamic Acid/TA) is an NSAID that has anti-tumor proliferative effects. It works through targeting specificity protein (Sp) transcription factors that assist cancer cells in inhibiting apoptosis. Our objective is to test TA and copper-TA (Cu-TA), a derivative of TA, to induce an anti-leukemic response. Methods: The T-cell ALL cell line CCRF-CEM was obtained from the American Type Culture Collection (Manassas, VA) and cells were cultured as per the supplier's instructions. A cell viability assay was performed in which cells were plated in a 96-well plate and treated with increasing concentrations of TA and Cu-TA. After 48-hours, the cells were lysed, and the amount of ATP in the cells was measured using luminescence. Using this data, IC50 values were calculated. Results: The IC50 values showed both TA and Cu-TA had anti-cancer proliferative effects. Cu-TA was 15 times more potent than TA in its ability to kill CCRF-CEM cells. Conclusion: Our results demonstrate that Cu-TA is more effective than TA for killing CCRF-CEM cells. This study suggests better implications of Cu-TA in ALL therapy, if further tested using pre-clinical models.Item Assessing the cytotoxicity of investigational agent for cancer therapy against non-malignant cells(2020) Patel, Krishna; Mukka, Lasya; Sankpal, Umesh; Basha, Riyaz; Siraj, SohailBackground: The treatment of cancer requires chemotherapy (ChT). Most of ChT agents exhibit unwanted side-effect and cause damage to healthy cells. Side effects from commonly used ChT agents are leaving pediatric cancer survivors with lasting damage to organ systems, specifically the heart. Studies conducted by our group demonstrated the anti-cancer activity of clotam (tolfenamic acid-TA) and copper-clotam (Cu-TA). Cu-TA is showing higher cytotoxicity against cancer cells even at much lower dose than TA in pancreatic cancer cells. Our long term objective is to test these agents to sensitize cancer cells to ChT. Methods: Cardiomyocytes H9c2 (cell line derived from rat heart tissue) originally obtained from the American Type Culture Collection (Manassas, VA) were cultured as per the supplier's instructions. H9c2 cells were treated with TA or Cu-TA or Doxorubicin and combinations (for example, TA and Doxorubicin) and cell viability assay was measured using CellTiter-Glo (Promega) kit at 48 hours post-treatment following manufacturer's instructions. Results & Conclusion: We found that TA or Cu-TA are not inducing toxicity in H9c2 cells at tested doses. TA kept more cells alive in conjunction with Doxorubicin than did the control. Our studies also show that H9c2 cells are not toxic to IC50 values of TA or Cu-TA determined with cancer cells. These results provide evidence that the tested investigational gents are not inducing toxicity in cardiomyocytes at tested doses and supports use of these agents in combination therapy with ChT.Item Association of Specificity Proteins and Survivin in Colon Adenocarcinoma with an Emphasis on Race/Ethnicity(2020) Basha, Riyaz; Kurri, Ananya; Mahajan, AnishaPurpose: Colorectal cancers are the third most common group of cancers worldwide in incidence and mortality, with the most prevalent of those being colon adenocarcinoma (COAD). Mutations in Specificity protein 1 (Sp1) and survivin (baculoviral inhibitor of apoptosis repeat-containing 5) have been well associated with tumorigenesis, however their impact on COAD prognosis remains unclear. The purpose of this study was to evaluate the expression levels of Sp1 and survivin in COAD clinical specimens, their impact on patient survival rates, and association with racial/ethnic disparities. Methods: Data was analyzed using two online databases: 'R2 genomics visualization platform' and 'University of Alabama Cancer Database (UALCAN)'. R2 was used to generate Kaplan-Meier curves for COAD patients with tumors expressing Sp1 and survivin (n=155 patients). UALCAN was used to generate COAD patient survival probabilities in association with race/ethnicity (n=256 patients) of African American (AA), Asian, and Caucasian descent. Results: Sp1 and survivin are overexpressed in COAD tumors and the survival curves demonstrated a link between high levels of Sp1 and survivin expression in COAD patients with a significantly poorer prognosis compared to patients with low levels of expression (Sp1, p=0.0047; survivin, p=0.041). Additionally, the survival curves revealed racial/ethnic disparities. The overexpression of Sp1 and survivin is prevalent among African American patients, correlating with poorer outcomes. Conclusion: The overexpression of Sp1 and survivin is significantly associated with poor prognosis in COAD patients, especially in African Americans. Targeting these markers can improve survival outcomes in COAD patients and address cancer health disparities.Item Bioengineered Liposomal Platform for Bone Metastatic Prostate Cancer(2020) Joshi, Rohan; Ranjan, Amalendu; Vishwanatha, Jamboor; Wang, Jianmei; Halbert-Hoshikawa, Jason; Desai, Priyanka; Lampe, Jana B.Purpose: Despite the success in treating early-stage prostate cancer (PCa), the outcomes for metastatic disease are far from ideal. Once cancer reaches distant sites, the five-year overall survival rate drops to 28%. For 90% of patients with advanced PCa, skeletal metastasis is the primary destination. To address the unmet medical need of bone-metastatic prostate cancer, we have engineered a liposomal platform to deliver a chemotherapeutic directly to the bone. Methods: First, a bone-targeting moiety with a high affinity for calcium of the hydroxyapatite in bone was conjugated to one of the lipids and characterized using H NMR, P NMR, and FTIR. Next, we incorporated the conjugate and a chemotherapeutic cargo into the liposome using a microfluidic, nanoprecipitation method. We characterized our nanoparticles using dynamic light scattering, transmission electron microscopy, and nanotracking analysis. Results : Our average nanoparticle size was 150 nm ± 2.50 with a polydispersity index (PDI) of less than 0.2 ± 0.22 and a zeta potential of 28.18 ± 1.71. Drug loading and encapsulation efficiency will be determined using LC/MS. Other characterization includes in vitro uptake studies, cytotoxicity studies in C4-2B and mPC3 cell lines, and in vivo biodistribution studies. Conclusions: We hypothesize that our liposome will ameliorate bone damage caused by metastatic PCa, inhibit PCa differentiation and proliferation, and stimulate apoptosis of PCa cells. Our overall objective is to improve the quality of life by reducing off-target side-effects and extend the overall survival rate of bone-metastatic prostate cancer patients.Item Case report of suspected primary pulmonary choriocarcinoma in a 43 year old male presenting for treatment of H. pylori(2020) Troutman, Monte; Nguyen, Ryan; Roy, Joyce; Young, MatthewBACKGROUND: Choriocarcinoma is a rare cancer in males and is usually derived from the testicular intratubular germ cells. Extra-gonadal origins of the disease are possible but even more rare. Previous population analysis has shown the overall rate to be approximately 0.022 per 100,000. Among these, mediastinal-pulmonary origin is among the more common derivations and carries a poor prognosis. CASE INFORMATION: We present a case of a 43 year old male who presented to the gastrointestinal service for treatment of positive H. pylori from his primary care physician after a work up for abdominal pain, nausea and vomiting. A chest x-ray ordered for complaint of hemoptysis on intake history and physical revealed a large mediastinal mass and many disseminated opacities suspicious for metastatic disease. Further work-up revealed the lesion, originally thought to be squamous cell in origin, to be choriocarcinoma and a negative testicular ultrasound, despite a beta-hcg of over 10,000, led to a presumptive diagnosis of primary pulmonary choriocarcinoma (PCC). CONCLUSIONS: PCC is not entirely well studied due to its rarity and our case serves to illuminate an unusual presentation of a rare disease in a patient presenting to primary care with a very common complaint. Understanding of rare diseases and their warning symptoms serves to better prepare clinicians to catch rare and potentially lethal conditions that might otherwise be missed and lead to devastating consequences for patients.Item Case Report: Rectourethral fistula, a rare complication following prostate cancer external beam radiation and brachytherapy(2020) Hey, Wayne; Kulp, DennisBackground: Prostate cancer is the second most common cancer in men; 11% of men will receive a diagnosis of prostate cancer throughout their lifetime. In most cases, the cancer is asymptomatic and localized. Because of its indolent growth, many treatment modalities are available including radical prostatectomy, external beam radiation, brachytherapy, cryotherapy, and thermal ablation. Post-operative complications of these procedures include erectile dysfunction, urinary incontinence, urethral stenosis, and rectourethral fistula (RUF). RUF is an abnormal connection allowing passage of contents between the bladder and rectum. This rare and serious complication typically presents in older patients after transurethral resection of the prostate or post-radiation biopsy and requires extensive surgical salvage or diversion to repair. Case Presentation: A 49-year-old male with a past medical history of erectile dysfunction and elevated was diagnosed with prostate cancer following a biopsy showing Gleason Score 3+4=7 in 1/12 cores and Gleason 6 in 1/12 cores. He was referred to oncology and subsequently underwent external beam radiotherapy and brachytherapy with radiation seed placement. One year later, he presented to the clinic with pneumaturia, urinary diarrhea, and incontinence per urethra. His presentation suggested an RUF confirmed by cystoscopy which showed a posterior urethral tear immediately distal to the external urethral sphincter at the 7 o'clock position. The patient was referred for imaging and surgical evaluation for further management. Conclusion: Here we present the rare complication of rectourethral fistula formation in a young patient after external beam radiation in conjunction with brachytherapy.Item Clinical and radiological response to combined BRAF and MEK inhibitors therapy in a case of recurrent, progressive pleomorphic xanthoastrocytoma (PXA).(2020) Zhu, Jay-Jiguang; Ware, Cornelius; Bhartacharjee, Meena; Arevalo-Espejo, Octavio; Blanco, Angel; Tandon, Nitin; Kata, KarolinaBackground: BRAF gene mutations are well documented in a subset of gliomas, including pleomorphic xanthoastrocytoma (PXA), ganglioglioma, pilocytic astrocytoma, and epithelioid glioblastoma. PXA is rare, accounting for less than 1% of all astrocytic tumors, and two-thirds harbor a specific BRAF point mutation at V600E. Although the development of targeted BRAF inhibitors has dramatically improved the clinical outcomes for patients with BRAF V600E mutant tumors, such as melanoma, resistance develops in the majority of cases. Additional treatment with a MEK inhibitor could improve tumor control and survival. Application of dual inhibitors in PXA is rarely reported. Case Information: We report a case of 29-year-old woman with recurrent PXA with BRAF V600E mutation whose tumor was resistant to standard and salvage treatments including resections, thermal ablation, chemotherapy, and radiation, with partial response for 68 months. With disease progression while on temozolomide, a targeted treatment with combined BRAF inhibitor vemurafenib (Zelboraf) and MEK inhibitor cobimetinib (Cotellic) were initiated. The patient demonstrated significant clinical and radiological response with no disease progression for 10 months at time of this presentation. She continues therapy with the combined inhibitor therapy, with minimal side effects. Conclusions: PXA poses a therapeutic challenge due to its rarity, lack of consensus guidelines for treatment at recurrence, and no effective chemotherapeutic drugs. This case report describing significant response is encouraging. It adds to a small number of published reports highlighting the utility of BRAF and MEK combined inhibitor therapy in refractory PXA.Item Correlating DCE-MRI Vascular Changes and T2-MRI Contour Changes of the Muscles of Swallowing in Patients with Osteoradionecrosis of the Mandible following Intensity-Modulated Radiation Therapy for Head and Neck Cancers.(2020) Mohamed, Abdallah; Fuller, Clifton; Cooksey, LukePURPOSE: Radiotherapy is a treatment modality that is curative for the treatment of many head and neck cancers and is a mainstay of the standard treatment regimen of these cancers. Though beneficial in most cases, radiotherapy in the head and neck area carries toxicity risks associated with treatment: dysphagia, chronic aspiration pneumonia, and osteoradionecrosis are considered amongst those with the most impact. Osteoradionecrosis (ORN), or death of bone tissue due to radiation, affects only a small percentage of those receiving radiotherapy. However, ORN carries significant risks and detriments to quality-of-life when it does occur. Our work in this area seeks to identify and correlate changes in Dynamic Contrast-Enhanced (DCE) MRI vascular parameters with changes in T2-MRI swallowing muscle contours in patients who have received a diagnosis of ORN following Intensity-Modulated Radiation Therapy (IMRT). METHODS: For 95 patients who received a diagnosis of ORN, swallowing muscles were precisely contoured on pre-treatment and during-treatment T2 MRI images. The images were then compiled with pre-treatment CT-based radiation plans and DCE-MRI images using a software called "Dicompyler." RESULTS/CONCLUSIONS: While the work is still on-going, preliminary observations have indicated it is likely the overall aim to create a registry for assessing patient risk of ORN development is very possible. Future direction should be to continue compiling and registering ORN patient data and to begin preliminary work of establishing parameters and algorithms that can be safely tested in patients for analysis of clinical usefulness.Item Delayed Methotrexate Excretion Due to Sequestration in a Thymic Cyst(2020) Deville, HeatherBackground: High-Dose Methotrexate (HD-MTX) is extremely effective in childhood cancers; yet, it has many side effects due to its toxic potential. It is important that HD-MTX levels are continuously monitored. The normal timeframe for HD-MTX clearance is 2-3 days. In most patients, the levels should decline as the kidneys filter the medicine from the blood; however, prolonged excretion can result from HD-MTX accumulating in "third spaces'', for example pleural effusions or ascites. Case Information: A 16-year-old female patient was admitted for HD-MTX for osteosarcoma in 2019. During her first cycle of HDMTX, she experienced delayed clearance of MTX taking approximately 7.00 days, requiring prolonged hospitalization for drug level monitoring as well as monitoring for renal toxicity. Over the next two months, her clearance remained prolonged at 5.95 days and 7.08 days. Six weeks later, the patient presented to the clinic with chest pain. Upon evaluation, a CT angiogram revealed an elongated cystic structure in the superior mediastinum. The cyst was surgically removed. The patient cleared her next two scheduled HD-MTX treatments at 10- and 11-weeks post-diagnosis, in 2.66 and 2.93 days, respectively. Conclusions: This case study brings to light a rare occurrence of MTX sequestration within a pre-existing benign thymic cyst, leading to prolonged time to MTX clearance, prolonged hospitalization, and extended leucovorin rescue. It would be prudent to consider imaging patients with persistent delayed MTX excretion, looking for unusual areas where 3rd spacing may occur.Item Early Recurrent Granulosa Cell Neoplasm: a Case Report(2020) Moorhead, AvaA 61 year-old woman who has a history of a granulosa cell neoplasm (GCT), removed 1 year prior, presents to the office with increasing abdominal girth and severe limitations in bowel habits. She had been chronically constipated with difficulty walking and transferring secondary to pelvic and abdominal pain. Her primary neoplasm was excised at 15cm in conjunction with a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Upon imaging in August 2019, a new mass was seen measuring at 15cm with septations and loculations; suspicious for a possible recurrent tumor. Surgical excision was planned and executed without morcellation. Extensive carcinomatosis of the small and large bowel were seen, necessitating 2 bowel resections that were successful but leaving the patient with a temporary ileostomy. To date, she has been inconsistent with follow-up and discussion of the necessity of chemotherapy is pending. This patient is unusual in that her GCT was malignant and recurrent, but also the speed at which it returned, only 1.5 years later; both factors being unexpected for this type of tumor.Item Effects of Ionizing Radiation on Human Triple Negative Breast Cancer(2020) Joshi, Rohan; Chaudhary, Pankaj; Jones, Harlan; Choe, Jamie Y.Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype which exhibits high rates of metastasis. Due to lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 receptor (HER2), TNBC is not responsive to hormonal treatment and currently lacks targeted therapies. Radiation is an important component of cancer therapy and used clinically in combination with chemotherapy and/or surgery for TNBC patients. Specialized extracellular vesicles called exosomes are involved in intercellular communication and postulated to play roles in tumor metastasis. In this study, we evaluate effects of single-dose ionizing radiation on the proliferation and release of exosomes from three human TNBC cell lines (MDA-MB-231, CAL-51, HCC-1806). TNBC cells were cultured and irradiated with 8.6 Gy. Exosomes were isolated 72h post-irradiation using differential ultracentrifugation and evaluated for size and purity. Nanoparticle tracking analysis (NTA) quantified exosomes released by tumor cells. Western blot confirmed isolation of exosomes by determining expression of established exosome membrane protein markers. Ionizing radiation suppressed proliferation and migration of MDA-MB-231, CAL-51, and HCC-1806 based on in vitro wound-healing (scratch) assays. Total cell counts for irradiated vs. control conditions at the time of exosome isolation were statistically significant in CAL-51 (P=0.0205) and HCC-1806 (P=0.0261). Exosomes released per cell in response to radiation showed inconclusive trends. Our preliminary data demonstrates radiation is capable of depressing TNBC proliferation and warrants further exploration regarding radiation-induced effects on tumor-derived exosomes.Item Evaluation of Gait Abnormalities in Patients with a History of Retinoblastoma(2020) Bowman, William; Goodrich, Toyya; Akers, Lauren; Vachon, BradBackground: The incidence of metastatic retinoblastoma (Rb) is rare, occurring in about 5% of Rb cases. This makes recognition and diagnosis of these patients challenging. The treatment outlook for metastatic Rb is less promising than that of primary malignancy. Current studies estimate 80-90% survival rates for patients having metastatic disease without central nervous system (CNS) involvement, and a mere 8% with CNS involvement. Case Information: Case #1: 6-year-old female with history of unilateral Rb that was ultimately treated with enucleation followed by chemotherapy. She presented to clinic seven weeks after completing treatment with complaint of new limp. Clinical exam was unremarkable, so no further evaluation was recommended. Symptoms progressed to include intermittent fevers and increasing low back pain. Two months after her limp began, a diagnosis of metastatic Rb with dissemination to bone was established. Case #2: 15-year-old male with history of bilateral Rb diagnosed and treated in infancy. He presented to an Emergency Department complaining of intense leg pain. Oncological workup was not recommended. Symptoms progressed to include intermittent fevers and worsening leg pain. Five months after the initial complaint, a diagnosis of metastatic Rb with dissemination to bone was established. Conclusion: The prognosis of metastatic retinoblastoma correlates highly with extent of dissemination. Therefore, early recognition and initiation of treatment is essential to enhance patient survival. These case presentations suggest that insidious onset of gait abnormalities in patients with history of Rb may be an early indicator of metastatic disease and warrants prompt evaluation.Item Exosome clocked hybrid nanosystem for targeted TNBC therapy(2020) Ranjan, Amalendu; Vishwanatha, Jamboor; Lampe, Jana B.; Joshi, RohanBackground: Metastasis is the leading cause of death in breast cancer worldwide. In recent years, it has been found that mesenchymal stem cells (MSC) cells and their exosomes play a role in the tumor microenvironment and they may have tumor homing properties. Using this information, our plan was to bioengineer MSC exosome-coated drug loaded polymeric nanoparticles to deliver our chemotherapeutic drug. Methods: To isolate the MSC exosomes we grew the cells in exosome free media and used ultracentrifugation with the highest speed at 100,000 g for isolation. We used Dynamic Light Scattering (DLS) for size analysis, polydispersity index (PDI) and zeta potential (ZP). PLGA polymeric nanoparticles were made using the Nanoassembler which uses microfluidics to make nanoparticles. Their size, PDI and ZP was also obtained using DLS and NTA. To make the coated NP we used the extrusion method. Results: The MSC exosomes and NP had the expected size. Our exosome sample was positive for exosomal proteins and negative for all other extracellular vesicles. After extrusion the ZP of our sample tells us that our sample was coated in exosomal membrane. Our sample was future purified using centrifugation and were loaded with Doxorubicin. Conclusion: We were able to make MSC exosome-coated drug loaded polymeric nanoparticles and show that they were stable and uniform in size. In the future we plan to do more cell studies to look at cell viability and toxicity as well as more compressive animal studies.Item Fertility Preservation and Chemotherapy Treatment in A Case of Pelvic Rhabdomyosarcoma: A Case Study(2020) Bowman, William; Dorton, CodyBackground: Infertility is a common problem for patients undergoing cancer treatment. Agents such as cyclophosphamide and others are known to be gonadotoxic as is radiation. The loss of fertility is psychologically traumatic to patients who hope to resume a normal life following their treatment. In addition, female patients may undergo premature menopause after chemotherapy. Case Information: A 21-year-old female presented with a pelvic mass and was diagnosed to have rhabdomyosarcoma, stage 3. She was scheduled to receive chemotherapy with vincristine, actinomycin-D, and cyclophosphamide, and radiation therapy. Before commencing treatment she inquired about fertility preservation and was allowed 2 weeks for egg retrieval before start of chemotherapy. Oocyte preservation was successful, and she then began 42 weeks of chemotherapy as originally planned. She achieved remission of her cancer and remains free of disease since completion of treatment over three years ago. She experienced primary ovarian failure as a consequence of cancer treatment but may have future prospect of parenthood due to the opportunity of selective egg retrieval and freezing before chemotherapy. Conclusions: Physicians should discuss with their patients the risks of infertility resulting from cancer therapy and offer fertility preservation options when feasible. While not applicable to all with aggressive cancers there may be circumstances such as described when a window of time may be allowed for an attempt at fertility preservationItem Functional characterization of a macrophage-polarizing agent loaded in reconstituted high-density lipoprotein nanoparticles for cancer immunotherapy(2020) Lacko, Andras G.; Sabnis, Nirupama; Dossou, AkpedjePurpose: The murine stimulator of interferon genes agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) has been successfully used to modulate the function of macrophages from an immunosuppressive phenotype (M2) to a proinflammatory phenotype (M1). Drugs, such as DMXAA, that facilitate this phenotype reversal are particularly relevant in cancer therapy as the immunosuppressive phenotype of tumor-associated macrophages (TAMs) contributes to tumor progression. This functional reprogramming of TAMs by drugs, including DMXAA, has been reported to facilitate sustained tumor regression. However, drug targeting strategies are needed to specifically deliver reversal agents to TAMs and avoid off-target effects. In this study, we investigated the physicochemical characteristics, as well as phenotype reversal capability of DMXAA encapsulated in the biocompatible reconstituted high-density lipoprotein (rHDL) nanoparticles. Methods: The DMXAA-loaded rHDL (rHDL-DMXAA) was prepared using an enhanced microfluidics apparatus. Dynamic light scattering (DLS) and fast protein liquid chromatography (FPLC) were used to assess particle size and preparation homogeneity. M1 and M2 markers expression by murine macrophages were assessed via western blot and ELISA. Results: While DLS indicated particles of 33.9 ± 14 nm diameter size, the FPLC profile of preparation indicated a homogeneous preparation with an estimated particle molecular weight of 132 kDa. Upon treatment with rHDL-DMXAA, the macrophages showed increased M1 marker expression. Conclusion: rHDL-DMXAA induced an M1 phenotype in macrophages and its characteristics suggest a potential for intratumoral accumulation. Thus, the rHDL-DMXAA represents a functional proof-of-concept strategy to target macrophages with implications in cancer immunotherapy.
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