The National Cancer Institution reported over 80,000 diagnoses of bladder cancer (BCa) in the United States in 2018. Despite these numbers, minimal research toward developing new diagnostic techniques and treatment options are underway. Evidence suggests a significant increase in non-specific a-naphthyl acetateesterase levels in BCa patient’s urine. There has been little research focused on identification of the esterase present. It is also suggested that elevated oxidative stress resulting in production of reactive oxygen species (ROS) is common in tumorigenic bladder cells as a result of increased metabolic activity. Oxidized protein hydrolase (OPH) is an 80kD serine protease, previously found to be elevated in many other types of cancer. OPH degrades proteins damaged by ROS and also exhibits a highly specific esterase activity toward (AcApNA) N-acetyl-alanyl-p-nitroanilide and ANAA (α-naphthyl N-acetylalaninate) containing substrate. Investigation of OPH expression in BCa could result in development of new diagnostic techniques and possible application toward prodrugs targeting cells with elevated ROS and/or OPH. Due to lack of commercial OPH, a positive control for this protein is needed for testing. To do this E. coli(BL-21 DE-3) were cultured and inserted with pET-21a (+) plasmids containing a human OPH gene insert prior to a His7 tag. After being selectively grown on ampicillin media, the bacteria were induced by IPTG and digested using lysozyme. The soluble rOPH suspended in the supernatant was separated from the pellet by centrifugation and further purified using Ni-NTA resin chromatography columns specific for the His7 tag sequence. The UM-UC-3 bladder cancer cell line, commonly used in published research to screen efficiency of chemotherapeutics, were cultured in accordance to ATCC. These cells were then compared against none tumorigenic bladder cancer cells and rOPH in a series of tests. Sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis (SDS-PAGE) were transferred for western blot analysis using antibodies specific for human OPH to investigate the expression levels present in cells. Native-PAGE electrophoresis showed OPH esterase activity across these cells using S-ANAA substrate as a specific esterase colorimetric stain. With these results, possible treatment options can be investigated with use of novel prodrug chemotherapy specifically targeting OPH in BCa cells, ultimately leading to apoptosis in effected cells. These events may also lead to possible biomarkers used for easier and earlier diagnosis of BCa across various spectrums.

Multiple myeloma is characterized by proliferation of plasma cells in the bone marrow, producing monoclonal immunoglobulin. It accounts for 17% of hematologic malignancies in the US. Diagnosis is often suspected in the setting of bone lytic lesions, anemia, hypercalcemia or renal failure. Rarely, multiple myeloma can present with soft tissue involvement which can be difficult to diagnose. Below we present one such presentation. Our patient is a 53-year-old who was initially diagnosed with multiple myeloma six years back when he presented to hospital with back and right leg pain. On admission he was found to have multiple lytic lesions involving the appendicular and axial skeleton. On further workup, bone marrow biopsy showed 30% plasma cells with IgG kappa monoclonal protein elevation. Patient was diagnosed with ISS stage II multiple myeloma. He was treated with standard regimen with Velcade, Revlimid and dexamethasone with excellent response. Patient was evaluated for stem cell transplant however did not qualify for it due to social challenges. Patient was continued on maintenance therapy with Velcade and Revlimid for 8 cycles prior to clinical relapse with lytic lesions in the C-spine. At this point patient was switched to different therapeutic regimen with pomalidomide, carfilzomib and dexamethasone and had excellent response for 35 cycles on this regimen. Patient had interruption in treatment for 3 months due to other medical comorbidities. A repeat bone marrow biopsy which was done in November of 2019 revealed extensive bone marrow involvement with 70% plasma cells concerning for relapse. Patient was started on single agent daratumumab in December 2019 however had a difficult course interrupted by right-sided abdominal pain, persistent nausea and decreased appetite requiring hospital admission. Further workup revealed a 2.7 cm lesion in the liver as well as a 4.9 x 7.3 cm T11 left paraspinal soft tissue mass. Biopsy of the liver lesion revealed sheets of kappa restricted abnormal plasma cells concerning for progression of disease. Given the involvement of the visceral organ and the extent of his disease, it was decided to switch patient's treatment from single agent daratumumab to a multi agent chemotherapy regimen with dexamethasone, cyclophosphamide, etoposide and cisplatin. Patient received his 1st cycle inpatient and had marked symptomatic improvement and was discharged home. His M-protein spike reduced from 3.9 to 1.8 g/dl post once cycle of treatment. Soft tissue involvement by multiple myeloma is rare event. Though malignant plasma cells may diffusely infiltrate the liver parenchyma, the nodular spread is unique. In review by Talamo et al, out of 2,584 patients with MM, only 11 had liver plasmacytomas. This phenomenon is driven by lack of expression of adhesion molecules, increased heparanase-1 expression and loss of chemokine receptors on myeloma cells. Such alterations in cell architecture lead to more aggressive disease behavior. At present time treatment for this unique patient population does not differ from other MM cases. It is important for clinicians to recognize the possibility of such event.

Urinary bladder paraganglioma (UBP) is a rare neuroendocrine neoplasm. It accounts for less than 1% of urinary bladder tumors and less than 6% among all types of paragangliomas. More commonly, UBP occurs in the female population aged 20-40 years old. UBP is classified into functional and non-functional types, and the majority is functional, leading to symptoms and signs of excess catecholamine, including hypertension, palpitation, syncope, and headache. Non-functional UBP comprises about 15% of UBPs and lacks the excess secretion of catecholamine, which often leads to misdiagnosis as urothelial cancer due to its rarity and nonspecific symptoms - increased urinary frequency/urgency and painless gross hematuria. Here, we present a rare case of a non-functional UBP. A 65-year-old male with BPH presented to ER with a 6-month history of urinary retention. He also was experiencing intermittent hematuria and dysuria during this time but otherwise remained asymptomatic without headache, dyspnea, wheezing, or diarrhea. Physical exam showed normal BP and no suprapubic tenderness on palpation. UA showed gross hematuria. Subsequent cystoscopy showed thickening of the bladder dome and an 8 mm lesion. Transurethral resection of bladder tumor (TURBT) was performed, and pathology showed 1 cm tumor confined to submucosa with questionable margins. Chromogranin, synaptophysin, CD56, GATA3, CD10 were stained positive; cytokeratin AE1/AE3, cytokeratin 34betaE12, SOX10, S100, and calretinin were negative. From morphology and immunochemistry, the diagnosis of UBP was made. Free metanephrine, plasma normetanephrine, 24-hour urine metanephrine and normetanephrine levels were not elevated. Post-TURBT MRI abdomen showed no other suspicious lesions. A wide re-resection of the bladder dome was performed due to the questionable margins from the initial surgery, and pathology showed benign bladder tissue with unremarkable immunostains, indicating no overt features of residual paraganglioma. Due to its paucity and uncertain biological behavior, the prognosis of UBP is not well established. While most UBP are benign, 10-15% of cases are malignant. High expression of VEGF and or abnormal vessel architecture in the tumor cells raise suspicion of malignancy. However, typically, definitive evidence of malignancy in paraganglioma is its invasion of adjacent organs or distant metastasis. The local recurrence rate ranges from 5-15%, thus necessitating long-term surveillance for 10-years. Systemic chemotherapy, including cyclophosphamide, vincristine, dacarbazine (CVD), or temozolomide, is necessary for distant metastatic or symptomatic disease. Iobenguane I-131 or Lutathera can be utilized with positive MIBG or 68Ga DOTATATE scan, respectively. Otherwise, surgical extirpation remains the choice of curative intent, and a multidisciplinary approach consisting of urologists, medical/radiation oncologists, and endocrinologists would be warranted for this rare entity of disease.

Amyloidosis involves extracellular deposition of abnormal proteins/fibrils with potential end organ damage. AL type amyloidosis is one subtype and a clonal plasma cell disorder. A 74-year-old completely asymptomatic male presented with progressive renal dysfunction. Work up with serum protein electrophoresis (SPEP) and immunofixation revealed monoclonal IgG Lamda spike of 1.1 g/dL. Urine protein electrophoresis noted Bence Jones proteins. Notable labs, hemoglobin 10.6 g/dL, calcium was 8.2 mg/dL, and creatinine 2.4 mg/dL. Quantitative immunoglobulins IgA, IgG, and IgM, were 59 mg/dL, 1,939 mg/dL, and 23 mg/dL, respectively. Lambda and Kappa free light chains 26.37 mg/L and 127.87 mg/L, respectively, with a ratio of 0.21. Skeletal survey noted a 4 mm lucency of the left frontal bone. Bone marrow biopsy confirmed 21% plasma cells. Renal biopsy revealed AL lambda light chain confirming final diagnosis AL Lambda light chain Amyloidosis and IgG Lambda Multiple Myeloma. Treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone initiated. His clinical course was complicated by COVID 19 infection prior to treatment initiation and with congestive heart failure secondary to cardiac amyloidosis (elevated Troponin and Brain Natriuretic Peptide level) during induction therapy requiring hospitalization, diuresis and optimization of cardiac medications. Very Good Partial Response (VGPR) noted after 2 cycles and near Complete Response (CR) after 4 cycles. Patient was evaluated and approved for Stem cell transplant (SCT) but decided against SCT and has now proceeded to single agent daratumumab maintenance. Amyloidosis is an uncommon disease seen in older adults (median age 64) with deposition of fibrils composed of low molecular weight subunits derived from normal proteins. Various subtypes and protien/fibrils include AL amyloidosis (immunoglobulin light chain), hereditary/ familial transthyretin amyloidosis (mutated transthyretin, apolipoprotien, fibrinogen A, lysozyme), wildtype transthyretin Amyoidosis/senile amyloidosis (unmutated transthyretin) and AA amyloidosis (serum amyloid A fibril). AL amyloidosis is a systemic disorder that presents with nephrotic syndrome or restrictive cardiomyopathy (as in this case). Other presentations involve peripheral neuropathy, hepatomegaly, macroglossia, arthropathy with “shoulder pad” sign, bleeding diathesis, purpura including “racoon eyes”. Biopsy of the affected organ (kidney, liver, fat pad aspirate, bone marrow) with Congo red staining confirms the histologic diagnosis. Amyloid light chains can be confirmed with proteomic analysis (mass spectrometry or immuno-electron-microscopy). AL amyloidosis treatment entails high dose chemotherapy and autologous SCT. Long term prognosis in advanced stage is poor. Survival can be short (4-6 months), heart failure causing about 50% of deaths. Daratumumab-regimens offer a 40-55% CR and with SCT data (83% five year and 50% ten-year survival) the outlook is improving.

Breast cancer is the most commonly diagnosed cancer in women with an estimated 287,850 cases in 2022. Approximately 684,000 deaths each year are associated with breast cancer across the world. Risk factors of breast cancer include increased estrogen exposure, family history of breast cancer, and environmental factors. Treatment of breast cancer is highly dependent on the presence of HER2, estrogen, and progesterone receptors. Breast cancers that present with increased receptors for estrogen, progesterone, and HER2 are typically the least aggressive and the easiest to treat. The percentage of cases in the United States associated with hormone receptor positive and HER-2 negative or positive are approximately 82%. Absence of receptors for estrogen, progesterone, and HER2 is known as triple negative breast cancer. In the United States, only about 10% of cases are associated with this form. However, it is considered the most aggressive and difficult to treat. Two emerging flavonoids known as CT1 and CT3 have shown cytotoxic activity against cell lines that represent some of the most common breast cancers: MCF7, MDA-MB-231, and SKBr3. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor and the compounds then underwent isolation and purification. The cells were then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 µM. MTT assays were then used to determine cell viability. MDA-MB-231, the most aggressive type of breast cancer cells, responded to both CT1 and CT3. The most profound cytotoxic effects of CT1 were seen with MCF7 and MDA-MB-231, while CT3 exhibited a greater toxicity against SKBr3 cells. Preliminary results indicate that CT1 and CT3 target the MEK-ERK signaling pathway. Further studies need to be completed to determine mechanistically how these compounds lead to receptor-independent toxicity.

Introduction: Oxidative stress is a disruption in the balance of free radicals and antioxidants. Cancer patients have very high levels of oxidative stress due to radiation and chemotherapy. This imbalance from the oxidative stress can stimulate cancerous growth, as well abnormal cellular growth. Oxidative stress is due, in part, to lipid per-oxidation from cancer treatments, generating electrophilic aldehydes that attack abnormal, as well as healthy cells. A way to combat the amount of oxidative stress to protect healthy cells is to increase antioxidant defenses through the diet. Antioxidants are chemicals that help stop free radical formation and prevent cell damage. Traditional high antioxidant foods include fruits, vegetables, low saturated- fats, and high fiber foods. During cancer treatments the patient generally has a decreased sense of appetite, as nausea and emesis are common side effects. A “treat” food, like a Reese’s peanut butter cup might be able to stimulate a cancer patient’s appetite, and thus meeting some of their much-needed dietary nutrients. By transforming this popular dessert treat into something that could aid with oxidative stress may be beneficial to this population. The objective of this study was to create an appetizing and nutritionally functional Reese’s peanut butter cup alternative with enhanced antioxidants. Methods: A common Reese’s cup recipe was taken and adapted for more nutrient rich ingredients. The milk chocolate of the original control recipe for Reese's cup was substituted in the variant dessert cup with dark chocolate cacao nibs. The peanut butter was replaced by tahini, and the sugar was replaced by dates in the control and variant, respectively. Proximate analyses for the nutritional content of both dessert cups was collected. Analyses included: Total cal/g using bomb calorimetry, antioxidant potential by a ferric reducing ability of plasma (FRAP), Soxhlet for lipid determination, kjeldahl for protein determination, and fiber via a ANKOM Fiber Analyzer. Results: Calories for the control yielded 5961 cal/g, and the variant, 6007.5 cal/g. The absorbance data for FRAP was 2.9996 and 4.5426, for the control and variant respectively. Lipid content was 46.65% for the control (% Ether Extract (Crude Fat)) and 46.9% for the variant (% Ether Extract (Crude Fat)). Protein content for the control was 6.25%, and 9.65% for the variant. Analysis for dietary fiber found insoluble dietary fiber to be 26.6% and soluble dietary fiber 0% for the control. The variant’s insoluble dietary fiber content was 21.4% and soluble dietary fiber 8.7%. Finally, dry matter was 98.6% for the control, and 97.4% for the variant. Conclusion: Data collected showed the greatest differences between antioxidants, fiber, and protein, with the variant having the highest percent content of each nutrient. This research has shown that a dessert alternative can support patients undergoing cancer therapies through the provision of necessary calories and antioxidants. Future research is needed to compare the specific fatty acid content of these two products

Pancoast tumors are a distinct entity seen mostly in non-small cell carcinoma of the lung. We present a case of a Pancoast tumor in newly diagnosed squamous cell carcinoma of the lung. A 56-year old female with a 40-pack year smoking history, presented with several weeks duration of right shoulder pain, radiating down her arm. Symptoms were aggravated with movement and slightly improved with rest and non-steroidal analgesics She had no other known medical history. Physical therapy provided little relief. Subsequently, magnetic resonance imaging (MRI) of the cervical spine from an outside facility revealed a large right apical lung mass, involving the T2 thoracic spine and sternum. She denied chest pain, shortness of breath, weight loss, or edema of the face or neck. Range of motion of right upper extremity was limited due to pain. Ptosis and miosis of the right eye were detected. Days after the MRI, the patient presented to the hospital for intractable right upper extremity pain. Comprehensive imaging including positron emission tomography scan and MRI of the brain were done. The right apical lung mass was suggestive of a Pancoast tumor, measuring 5.3 x 5.5 x 6.9 cm in size, extending into the medial portion of the upper mediastinum. The tumor abutted the apical pleura and partially encased the right subclavian artery. There was destruction of the first and second ribs and portions of the right T1 and T2 vertebral bodies along with right hilar and lower paratracheal adenopathy. Biopsy of the mass confirmed moderately differentiated, invasive squamous cell carcinoma of the lung, assessed to be Stage IIIB and unresectable. Pain control was achieved, and the patient was discharged. Treatment was initiated with concurrent radiation and chemotherapy with cisplatin and etoposide. Pancoast tumors, also known as superior sulcus tumors, were first noted in 1838 but not well defined at the time. In 1924 and 1932, American radiologist, Henry Pancoast, further described them as carcinomas of unknown origin of the chest apex. They occur in 3-5% of lung cancers, most commonly in non-small cell carcinoma. By definition, a Pancoast tumor must invade parietal pleura and cause pain, paresthesia, or neurologic dysfunction. Less than 50% of these tumors are resectable. They may involve the lower cervical and/or upper thoracic spines, first and second ribs, brachial plexus, and subclavian vessels. Involvement of paravertebral sympathetic chains can lead to Horner syndrome with a prevalence up to 40%. Neurologic compromise may cause upper extremity weakness, muscular atrophy, and paresthesia. In 5% of cases, they can cause spinal cord compression and paraplegia. Five-year survival is reported to be less than 10% if there is vertebral body invasion. In locally advanced lung cancers including Pancoast tumors, treatment can include neoadjuvant chemoradiation with subsequent resection. However due to the extensiveness and complexity of this patient’s tumors, resection was not amenable. Evaluation for Pancoast tumor may be warranted in those with lung cancer risk with acute musculoskeletal/neurologic complaints. Treatment is initiated promptly, based on stage and histology.

Multiple Myeloma is cancer of plasma cells and is known to be highly invasive. Multiple Myeloma makes up 1% of cancer diagnosis in western countries and affects men more predominantly than women. The American Cancer Association estimates that 32,110 new cases will be diagnosed in the United States in 2019. Lenalidomide is one of the main therapies used for multiple myeloma patients, but it has toxic side effects such as thrombocytopenia, neutropenia, and anemia. The purpose of the study is to investigate new cytotoxic agents for the treatment of multiple myeloma. In addition to lenalidomide alone, this study examined the effects of doxycycline alone and in combination with lenalidomide. Lenalidomide cell cultures were treated at concentrations from 0.5μM to 10μM on untreated 24 well plates and doxycycline concentration ranging from 10μM-80μM. Following incubation, cell viability was tested using MTT assay and the samples were analyzed using spectrophotometry. When compared to lenalidomide, doxycycline monotherapy showed a greater decrease in overall cell viability in preliminary results. Our results show that there is benefit of using 10μM of Doxycycline at higher concentration of 5μM and 10μM of lenalidomide. The potential decrease in the concentration of lenalidomide used by adding doxycycline, may reduce the toxic side effects of lenalidomide. Further studies are necessary to confirm these preliminary results and investigate the mechanism of action in order to determine optimal combinations of these drugs.

Considered the most common malignancy in women in the United States and second leading cause of cancer death among women, breast cancer has had a shift in paradigm of treatment within the recent years and undertaken significant research for new targeted treatment with a more molecular driven approach which has led to increased survival rates amongst women diagnosed with early stage breast cancer. The risk of recurrence however persists overtime, particularly in hormone receptor positive breast cancer, which has demonstrated recurrence rates as late as 30 years after initial diagnosis. This leads to a higher need for increased awareness of late recurrence rates in early stage breast cancer patients and reminds us to be wary of any new findings that in other patients may be considered as benign. We present a case of a 67-year-old female with remote history of locally advanced hormone positive breast cancer in 2005 who underwent mastectomy with lymph node dissection followed by adjuvant chemotherapy, radiation, and endocrine therapy for at least 8 years who presented to our clinic 18 years after initial diagnosis with an enlarging nodule in her neck. Patient underwent a thyroid ultrasound which showed a suspicious thyroid nodule concerning for malignancy classified as TIRADS-5. Further systemic imaging via PET-Scan demonstrated surrounding cervical lymphadenopathy adjacent to the thyroid nodule with increased fluorodeoxyglucose (FDG) avidity. She proceeded to undergo a thyroid fine needle biopsy, which was suspicious for malignancy. A repeat thyroid fine needle biopsy was obtained this time confirming metastatic breast cancer. Considering the rarity of such event, we proceeded with further testing of biopsied tissue via cancer type ID, which confirmed presence of metastatic breast cancer in the thyroid. Patient was informed of now metastatic breast cancer diagnosis with plans to start Faslodex and Ibrance. Unfortunately, she developed rapid disease progression with hospitalization due to a recurrent malignant pericardial effusion suggestive of visceral crisis requiring initiation on palliative chemotherapy with Carboplatin and Gemcitabine. Patient has been tolerating systemic chemotherapy well with interval clinical decrease of more than 50% in size of her surrounding cervical lymphadenopathy and resolution of pericardial effusion. The incidence of thyroid metastatic disease from breast cancer is very rare accounting for only 0.2% of fine needle biopsy aspirations. The most common sites of breast cancer metastasis include lung, bone, liver, and brain. On the other hand, the most common primary malignancies that can cause metastasis to the thyroid are kidney, gastrointestinal tract, and lung. However, as of 2018 around 42 cases of metastatic breast cancer found in the thyroid had been reported and it was also noted that metastatic thyroid involvement of breast cancer could be associated with a poor prognosis. This case represents the importance of being aware of the risk of late recurrence in hormone positive breast cancers, which in turn should result in a lower threshold for thorough workup of common clinical findings in these patients.

In 2019, cancer was the second leading cause of death in the United States. Colorectal cancer is the second most common cancer affecting both men and women. Colorectal screenings are an important preventive health service, with approximately half of cases detected through screening, improving life expectancy among those diagnosed. Previous research has noted differences in screening rates between racial or ethnic groups, with whites being screened at a higher rate than other racial and ethnic groups. Additionally, the prevalence of colorectal cancer is becoming more common among persons younger than 50 years old, prompting testing guidelines to be revised in 2018 that call for testing to begin at 45 instead of age 50. The purpose of this analysis is to investigate this issue further by examining differences in colorectal screening among various racial and ethnic groups. A cross-sectional study using the 2021 Behavioral Risk Factor Surveillance System for respondents from West Virginia and Oregon (combined) was used to examine colon cancer screening by various racial and ethnic populations. Individuals responding receipt of a colonoscopy or sigmoidoscopy were the primary outcome of interest. Racial and ethnic groups include whites-only, blacks-only, other races, multi-racial and those of Hispanic ethnicity. Additional covariates of interest were included in the analysis based on Andersen’s behavior model for health service utilization and includes predisposing (gender, age, education, marital status) enabling (insurance, employment status) need (body mass index, other types of cancers) factors. Bivariate and multivariate logistic regression analysis was used to examine these relationships. The study population included 2,831 adults who self-reported being screened for colon cancer. Overall 61% of white populations reported receipt of colon cancer screening compared to 54% of Black, 52% of Other, and 43% of Hispanic populations (p<0.00). Adjusting for additional covariates of interest, there were no significant differences between colon cancer screening among black populations compared to their white counterparts (aOR=.81; 95% CI=0.40-1.64). Age and education independently predicted being screened for colon cancer. Graduating from college increased an individual’s odds of being screened for colon cancer (OR= 2.1, 95% CI: 1.1-4.0). The odds also increased for individuals between the age of 55 to 64 (OR=4.2, 95% CI: 3.2-5.3) and ages 65 to 74 (OR=10.0, 95% CI: 6.8-14.8). Our study did not find significant differences in colon cancer screening by race/ethnicity in these two states. It is possible the racial and ethnic composition of the states contributed to the observed findings. West Virginia and Oregon are predominantly white. Smaller subpopulation groups within the national BRFSS dataset may not be sufficient to detect important differences in screenings. Furthermore, it is possible that several factors associated with screening (age, education) may be associated with race/ethnicity but are stronger predictors than race/ethnicity itself. Regular screening for colorectal cancer can help with detecting and treating colon cancer. Additional efforts to increase the general knowledge of colorectal cancer risks should be encouraged for individuals who did not graduate from college and are between 45 to 55 years old.