Cancer

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30050

Browse

Now showing 1 - 20 of 41

Case Report: Rectourethral fistula, a rare complication following prostate cancer external beam radiation and brachytherapy
(2020) Hey, Wayne; Kulp, Dennis
Background: 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.
Assessing the cytotoxicity of investigational agent for cancer therapy against non-malignant cells
(2020) Patel, Krishna; Mukka, Lasya; Sankpal, Umesh; Basha, Riyaz; Siraj, Sohail
Background: 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.
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, Luke
PURPOSE: 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.
Acute Lymphoblastic Leukemia in Adolescent & Young Adult Populations and Adherence to Protocol: A Case Study
(2020) Acosta, Melissa; Bowman, William; Albritton, Karen; Brewer, Shannon
Adolescent 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.
ALK Variations and Targeted Therapy in Pediatric Cancers at Cook Children's Medical Center
(2020) Ray, Anish; Swilling, Aubrey
Purpose: 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.
Targeted treatment for SHH+ Medulloblastoma in a pediatric patient with Gorlin Syndrome
(2020) Johnnidis, Melissa
Background: We present a case of metastatic medulloblastoma (MB) of the sonic hedgehog (SHH) molecular subgroup in a patient with previously undiagnosed Gorlin syndrome who was subsequently treated with Vismodegib, a hedgehog signaling pathway inhibitor. A 4-year-old female presented with a 6-month history of worsening ataxia. Imaging revealed a mass which was determined to be MB following biopsy. Genetic testing identified a PTCH1 gene mutation, consistent with the diagnosis of Gorlin syndrome. Objectives: To describe a case of a patient with Gorlin syndrome and metastatic medulloblastoma treated with Vismodegib, a targeted therapy for the SHH molecular subgroup of the tumor. Design/Methods: A chart review was performed for this single case study. Results: The tumor was determined to be SHH+ MB. With the Gorlin syndrome diagnosis, radiotherapy (RT) was not recommended due to the increased risk of developing basal cell carcinomas, which are common in the disease. The tumor was resistant to chemotherapy, so she started Vismodegib. The drug was initially beneficial until months later when further metastases were found on imaging. Conclusion: Mainstay treatment of MB consists of a combined-modality approach utilizing RT, which is risky in Gorlin syndrome patients. The use of Vismodegib as targeted therapy in our patient seemed promising, but the tumor progressed. We present this case to raise awareness to the potential complications of treating MB in those with Gorlin syndrome. Multi-institutional studies are required to determine whether the drug should be given to patients with Gorlin syndrome and SHH+ MB.
Hypertension Management in Cancer Patients Receiving Oral Chemotherapy or Hormonal Therapy
(2020) Monestime, Shanada; Wiliam, Jordan; Page, Ray; Magallon, Tara
Purpose: For cancer patients, primary care providers (PCP) are the mainstay for chronic disease management, such as hypertension. However, studies show many cancer patients do not have a PCP and prefer to see their specialists. This poses a greater concern to patients receiving oral chemotherapy or hormonal therapy (HT) due to fewer clinic visits, which puts hypertensive patients at risk for going untreated and undermanaged. This study evaluates hypertension management in patients receiving oral chemotherapy or HT. Methods: A retrospective chart review was conducted at a community oncology clinic to identify patients with a baseline blood pressure (BP) reading ? 120/80 mmHg and were newly initiated on oral chemotherapy or HT. Two to three BP readings recorded on separate visits were evaluated, averaged, and classified. Hypertension was defined by a systolic ? 140 or diastolic ? 90 mmHg or a systolic ? 130 or diastolic ? 80 mmHg with a diagnosis of chronic kidney disease or diabetes. Results: Of the 75 patients analyzed, 41% (n=31) of patients were found to be hypertensive. The systolic BP mean was 145 (range, 130-200) and the diastolic mean was 80 (range, 58-97) mmHg. Forty-eight percent (n=15) of hypertensive patients did not have hypertension listed as a condition on their electronic record and 26% (n =8) were not receiving antihypertensive agents. Conclusion: Over 1/3rd of patients receiving oral chemotherapy or HT were found to have unmanaged hypertension, which emphasizes the need for coordination of care amongst community oncology and primary care clinics.
Radical Resection of a Primary Inferior Vena Cava Leiomyosarcoma: A Case Study
(2020) Jackson, Terrence; Jeyarajah, Dhiresh; Sudanagunta, Sneha
Background: Leiomyosarcomas (LMS) are rare soft tissue tumors that arise from smooth muscle. Of the five different classifications of LMS, the vascular LMS subtype has a predilection for major blood vessels, such as the inferior vena cava (IVC). Primary IVC LMSs affect approximately 1/100,000 people and have a very poor prognosis. They can lead to an array of symptoms that are often associated with other etiologies and can be fatal if not diagnosed accurately and treated appropriately. Case information: A 54-year-old Caucasian female presented to the hepato-pancreatico-biliary surgery clinic for assessment of a firm right upper quadrant abdominal mass. Upon further workup and imaging, a large mass within her IVC was found. A biopsy of the mass showed necrotic tissue that was non-diagnostic but concerning for malignancy. This lead to a successful radical surgical resection of the mass and adjacent structures with placement of an IVC graft. Additionally, chemotherapy and radiation was started to decrease chances of recurrence. Conclusion: Leiomyosarcomas of large blood vessels are at a greater risk of affecting associated organs based on their location and extent of vessel involvement. Though primary vascular LMSs are rare, they can be treatable if they are correctly identified early in the disease progression. This case demonstrates that careful radical resection of a primary IVC LMS should be considered as a treatment modality, in addition to chemotherapy and radiation, for patients with these rare and potentially fatal tumors.
Retroperitoneal Cystic Lymphangioma: A Rare Presentation
(2020) Robbins, Daniel; Cameron, Benjamin; Elete, Kunal
Background: Lymphangiomas are benign congenital malformations of lymphatic vessels that are usually detected by the second year of life. They commonly affect the neck (75%) and axilla (20%) whereas fewer than 5% are reported to be intra-abdominal. Around 70% of intra-abdominal lymphangiomas are intraperitoneal in the small bowel mesentery but presented here is a case of a retroperitoneal mesenteric cystic lymphangioma. Case Information: A 55-year-old female with a surgical history of hysterectomy, bilateral oophorectomy, and laparoscopic adjustable gastric band was referred to surgery with a three-to-four-month history of bloating, early satiety, and lower abdominal discomfort. She denied changes in weight, appetite, or bowel movements. On previous abdominal CT, the lap-band appeared unremarkable, but there was an incidental discovery of a mass near the cecum and ascending colon. After a negative colonoscopy, she underwent repeat CT with contrast, which showed interval growth of the mass from 1.2x4.3 cm to 1.5x5.1 cm. Due to uncertainty of its nature and inaccessibility via percutaneous biopsy, a laparoscopic right hemicolectomy was recommended in addition to removal of the lap band, the latter of which was felt to be causing her symptoms. During surgery, the mass was identified in the right mesocolon and found to be cystic and multilobulated, and it was resected. Histopathology showed a CD34 positive cystic lesion filled with lymphoid nodules, confirming the diagnosis of cystic lymphangioma. Conclusion: This case illustrates a unique presentation of a condition rarely encountered in adulthood.
Young Female with Breast Cancer Found to Have Positive Mutations in ATM, PALB2, and FLCN (Birt-Hogg-Dube Syndrome)
(2020) Benichou, Chloe
Most breast cancers are sporadic, however, about 6% of breast cancers are attributed to single pathogenic variants of breast cancer susceptibility genes. A 25-year-old woman, positive for a previously known ATM mutation, presented with newly diagnosed right breast cancer. She had presented to her primary care physician after feeling a lump but was assured her ultrasound showed no worrisome findings due to her young age. Three months later, when her symptoms were worsening, she received a mammogram, ultrasound, and biopsy, which found her to have invasive ductal carcinoma and ductal carcinoma in situ of the right breast. The patient's family history included renal cell carcinoma, colon, prostate, and pancreatic cancer. A multi-gene panel was found to be positive for mutations in ATM, PALB2, and FLCN. The patient underwent chemotherapy and a modified radical mastectomy of the right breast and is being closely monitored while she completes radiation. The multiple mutations found in the patient's genome drastically increased her risk of developing breast cancer. Not only is the FLCN mutation uncommon, occurring in approximately 200 families world-wide, but the combination of three genetic mutations that increased her risk of breast cancer is exceptional. Due to the rarity of breast cancer in a woman under 30 and the paucity of multiple mutations, the patient's concerns were not given adequate attention and her cancer was undiagnosed for a prolonged period of time. This highlights the importance of genetic testing and close monitoring of high-risk patients influencing future care.
Spinal Metastasis
(2020) Gilani, Salaman; Zaman, Imaad
Classification: TCOM DO Student (1st Year) Department: TCOM: Internal Medicine & Geriatrics Authors: Salaman Gilani; Imaad Zaman Background: Metastatic lung cancer is cancer that originated in the lungs, but cancer cells separated from the main tumor are transmitted via lymphatic or hematologic pathways to other sites of the body. When a broken cell finds an attachment site it can begin to proliferate and form another mass with the same properties as the original tumor, often invading into the spaces of other organs and structures into the body. This can impair homeostasis and cause varying degrees of discomfort or pathologies. Lung cancers most often metastasize to nervous system structures (47%), bones (39%), and the liver (35%). Approximately two-thirds of patients with cancer will form a metastasis later on. Case Information: During dissection of an 80 year old male cadaver a spinal metastasis was found at the articulation of the 7th rib and the 7th thoracic vertebra. Conclusion: This report aims to further information regarding metastases to the spine from lung cancer. This pathology in our cadaver was selected due to its rarity and the opportunity it presents to learn about uncommon metastatic cancers. This metastasis was diverting the vena cava and thoracic duct in addition to displacing the spine from its resting position. Spinal metastases can cause pain, stability issues of the spine and depending on how far into the spine the cancer has invaded, can also present with neurological issues.
A Rare Case of Synchronous Gallbladder Metastasis Secondary to Gastric Adenocarcinoma
(2020) Jackson, Terrence; Nagatomo, Kei; Osman, Houssam; Jeyarajah, Dhiresh; Cho, Edward; Lim, Joseph
Background: 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.
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, Matthew
BACKGROUND: 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.
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, Karolina
Background: 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.
Long Range Forster Resonance Energy Transfer for rHDL Nanoparticles Drug Payload Estimation
(2020) Raut, Sangram; Shah, Sunil; Sabnis, Nirupama; Gryczynski, Zygmunt; Borejdo, Julian; Lacko, Andras G.; Gryczynski, Ignacy; Fudala, Rafal
Purpose: Over the last 30 years, there has been a dramatic increase in the application of fluorescence technology in the biomedical sciences. These advances include the application of fluorescence anisotropy for the assessment of the location and rigidity of the drug payload within the lipoprotein nanocomplexes. Forster Resonance Energy Transfer (FRET) is the long range through space interaction between the two chromophores (one energy donor and one energy acceptor) that very strongly depends on the chromophores separation. In the studies presented here, we selected the optimal combination and synthesized a FRET pair using doxorubicin within the rHDL nanoparticles as acceptor, and carboxyfluorescein linked to the rHDL via an 18-carbon lipid (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(carboxyfluorescein) [18:1 PE-CF]) as the donor. The emission spectra of donor (18:1 PE-CF) has a good overlap with the absorption spectra of an acceptor (doxorubicin), making this combination suitable for FRET studies. In this communication, we used our previous findings and FRET methodology for the assessment of the localization of the payload (doxorubicin) within the respective nanoparticles and their corresponding encapsulation/entrapment efficiencies. These findings validate the diameter and the three-dimensional array of the drug transporting (rHDL) nanoparticles, while additional measurements also allowed the estimation of the number of drug molecules carried by the individual nano-assemblies using non-destructive sampling procedure. The approach described here could likely to be extended to the investigation of the loading capacity of a variety of drug carrying nanostructures, including micellar nanoparticles and exosomes.
Prevalence of Mental Health Treatment Utilization in Cancer Survivors Diagnosed with Depression and/or Anxiety
(2020) Zhou, Zhengyang; Jann, Michael; Monestime, Shanada; Watson, Samantha
Purpose: Depression and anxiety are common mental health disorders in cancer survivors (CS) and could lead to increased morbidity and mortality if left untreated. Previous studies reported suboptimal antidepressant and anxiolytic pharmacotherapy use in CS compared to the general population (GP). To better understand the utilization of mental health services, this study evaluated the prevalence of pharmacotherapy and/or psychotherapy utilization for depression and/or anxiety in CS and the GP. Methods: A sample of 5,977 adults who participated in the National Health Interview Survey from 2012-2018 were included. All participants were diagnosed with anxiety and/or depression, defined by self-reported diagnosis and/or a score of ?13 on the Kessler 6 questionnaire. Descriptive analysis was performed to identify the prevalence of treatment utilization between CS and the GP. Results: The prevalence of receiving treatment for depression and/or anxiety was 61.9% and 60.2%, and between 2012 and 2018, the prevalence increased by 18.6% and 21.3% in the general and cancer populations respectively. Higher utilization of psychotherapy was found for anxiety and/or depression in the GP (50.3%) compared to CS (45.8%) whereas, pharmacotherapy use between the groups was similar (GP 29.4% and CS 31.9%). Conclusion: The inclusion of psychotherapy as a treatment option for depression and/or anxiety mitigate the disparities previously reported of lower treatment utilization in CS. Unfortunately, over one-third of participants received no form of mental health treatment. Clinicians need to recognize depression and/or anxiety and provide education and referrals to the GP and CS for mental health treatment options.
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, Krishna
Purpose: 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.
A rare case of nasal septum perforation in a breast cancer pt receiving Trastuzumab
(2020) Mohanaselvan, Arvindselvan
Trastuzumab 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.
Association of Specificity Proteins and Survivin in Colon Adenocarcinoma with an Emphasis on Race/Ethnicity
(2020) Basha, Riyaz; Kurri, Ananya; Mahajan, Anisha
Purpose: 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.
Lipoprotein Drug Delivery Initiative: A Translational research program employing the HDL and HDL mimetic drug delivery platform.
(2020) Raut, Sangram; Fudala, Rafal; Lacko, Andras G.; Saranya Conjeevaram Nagarajan, Bhavani; Dossou, Akpedie; Sabnis, Nirupama
Reconstituted (synthetic) lipoproteins and lipoprotein mimetics have been recognized as a superior biocompatible, targeted drug-delivery platform and thus have great potential in the treatment of a number of diseases. Our laboratory has been involved in exploiting the potential of rHDL nanoparticles (NPs) in cancer theranostics. Traditional chemotherapy is afflicted with long and short term side effects due to off target delivery of anti-cancer agents. In fact, often the side effects prove more damaging to the patients than the disease itself. Lipoprotein-based technologies could address this challenge due to their ability to selectively deliver their payload to cancer cells and tumors, via a receptor mediated mechanism. The therapeutic index (side effect profile) of a drug can thus be significantly improved by directing the selective delivery capabilities of the rHDL NPs toward tumors but not toward normal tissues. The contributions of our laboratory in facilitating the progress of this technology toward its clinical applications for the treatment of cancers are highlighted in this presentation.

Browse

Recent Submissions