Detection of Folate Receptor from FR+ Cancer Cells

The aim was to detect cancer cells by using folate–PEG-Biotin probe with fluorescently labeled streptavidin for targeted drug delivery of anti-cancer drugs and diagnose cancer cells. Folate-PEG-Biotin (synthesized by Dr. Henne and Mr.Rohan Patel) was purified by HighPeformanceLiquidChromatography (HPLC) analysis and with the help of Liquid Chromatography/Mass Spectrometry (LC/MS) its identity was confirmed. Folate is a basic composition of cell metabolism in both synthesis of DNA and proteins. Growing cancer cells require high level of folic acid. Folate Receptor-α (FR-α) is a membrane bound protein having high affinity for folic acid and serves to transport of folate into cells. Poly ethylene glycol work as spacer and reduce the steric hindrance between peptide and biotin. Biotin is a B-complex vitamin, which is having highest non-covalent affinity to streptavidin. Streptavidin biotin conjugate with folate helps in identifying and detection of cancer cells. We used fluorescently labeled streptavidin and incorporated it with Folate-PEG-Biotin Probe to detect cancer cells. We also studied cell capture by adding fluorescently labeled streptavidin along with 1000-fold excess of folic acid. This work was collaborated with Dr. Tim Gsell by using his high-resolution camera capable of capturing multi-fluorophore fluorescent images. Based on this study, further studies may include incorporation of releasable specific Anti-cancer drug to folate-PEG probe

Elevated PSA is associated with decreased physical function in men with prostate cancer

Studies have reported an association between cortisol and fatigue in multiple clinical populations, including prostate cancer (PCa). Treatment options for men with PCa, such as androgen deprivation therapy (ADT), come with a wide variety of adverse effects, including cancer-related fatigue, which greatly impacts quality of life (QoL). PURPOSE: Conduct a preliminary analysis on the association between cortisol, fatigue and QoL in men with PCa. METHODS: This study is part of an ongoing study to determine the impact of PCa and PCa treatment on fatigue and QoL approved by the University of Texas Health Science Center at San Antonio Intuitional Review Board. Twenty-one men (age: 69.1±11.55; BMI 28.99±4.78) with PCa were recruited from the Urology Clinic at the Medical Arts and Research Center in San Antonio, Texas. Participants provided ~2 mL of saliva for cortisol quantification using the passive drool technique. Saliva was immediately placed on ice and transferred within 4 hours to a freezer at -80oC until analysis. Cortisol was quantified using a commercially available salivary cortisol ELISA assay kit (Salimetrics, College Park, PA). Participants also completed three questionnaires: the Brief Fatigue Inventory, the Functional Assessment of Chronic Illness Therapy-Fatigue, and the SF-36. Pearson product moment correlation was performed to determine association between outcome variables. Student t-test was used to determine differences in cortisol, fatigue and QoL between men treated with ADT and men not treated with ADT. Significance was set at pRESULTS: Of the 21 participants, 9.5% (n=2) of participants had metastatic PCa, 4.8% (n=1) had castration-resistant PCa, 4.8% (n=1) had high-grade prostatic intraepithelial neoplasia, and 81% (n=17) had localized PCa. Twelve of the participants were being treated with ADT (57.14%). Significant correlation was observed between prostate specific antigen (PSA) and physical function (r=-0.728; p=.001), physical health (r=-0.729; p=.001), and emotional problems (r=-0.765; p=.001). No correlation was found between fatigue and cortisol levels. A comparison between groups revealed no significant difference in fatigue level between those on ADT versus those not on ADT. However, men not on ADT had a 28% higher average general health score. CONCLUSION: The results of this study suggest cortisol is not a strong physiological measure of fatigue in men with PCa. Furthermore, these preliminary data suggest that advanced cancer, as evident by elevated PSA, significantly impacts physical function and QoL in men with PCa. Further study for a more reliable biomarker of fatigue and interventions to improve QoL in men with PCa is warranted

COVID-19 Pandemic Effects on Individuals Physical Activity Levels and Emotional Health: A Descriptive Study

Texas is among one of the leading states of COVID-19 cases and fatalities which has impacted both healthy individuals and those living with preexisting chronic illnesses. Maintaining a healthy lifestyle and remaining physically active during a pandemic has challenged most, if not all, local residents. PURPOSE: to describe physical activity and mental health status in Texas residents with preexisting comorbidities and those without preexisting illnesses. METHODS: On July 2020, four months after the declaration of the global pandemic, an online survey was developed and distributed to various regions in Texas. A total of 156 respondents answered questions regarding their demographics, current health status, physical activity level, and mental health status prior to and after the COVID-19 pandemic declaration. A frequency distribution and descriptive statistical analyses was completed. A paired sample t-test was used to calculate means of responses pre- and post- the pandemic with significance level set at p\u3c0.05. RESULTS: Majority of respondents were white (84%), non Hispanic or Latino (54%), female (87%), under the age of 45 (57%) and reported having 1 or more diagnosed medical condition (61%). Physical activity levels were not significantly impacted in either subgroup. Although not significant, participants with 1 or more preexisting conditions decreased their activity level by 10% after declaration of the pandemic. Those without preexisting conditions increased their overall physical activity level by 9%. While physical activity level did not report significant changes after the COVID-19 pandemic, the psychological health of individuals, however, was significantly impacted. A significant increase in emotional distress such as feelings of nervousness and anxiousness were highly evident after the declared pandemic (p\u3c0.001). CONCLUSION: The present analysis confirms significant levels of stress after the declared current pandemic. Prolonged stress can lead to harm and disease and make a person more susceptible to infection which is why promoting physical activity and improving psychological health strategies for all Texas residents with emphasis to those with preexisting conditions should be a public health priority

Synergistic Effect of Exercise and Phellodendron Amurense on Muscle Mass Preservation in a Prostate Cancer Mouse Model

Muscle loss has detrimental effects on the body. It leads to a reduction in physical function, strength, endurance, and quality of life. In men with prostate cancer (PCa), a large percentage of men will suffer from muscle loss, a debilitating adverse effect caused by both the chronic illnesses or from the treatment of these illnesses. Studies have shown that the implementation of a routine exercise elicits muscle preservation in patients with PCa. Previously, our group has found that the natural product phellodendron amurense (PA) preserves muscle mass similar to exercise. PURPOSE: The purpose of this study is to test the hypothesis that combining PA and exercise will have a synergistic effect on muscle preservation and strength. METHOD: Twenty-four, 10-week-old transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were randomized into one of four study groups: Exercise (running wheel) group, PA group, exercise plus PA, or no treatment control. PA was pelleted into the feed at a dose of 600 mg/kg and provided ad lib. Body mass was measured each week. Fore limb and all limb grip strength was measured at baseline and end of study (Columbus Instruments, Columbus, OH). Mice completed 10 repetitions on the apparatus with the first five repetitions using only the forelimbs and the last five repetitions using all four limbs. After euthanasia, the right gastrocnemius and soleus were collected, cleaned and weighted. One way and two-way analysis of variance was performed with tukey’s post-hoc test. Significance was set at pRESULTS: Analysis of body weight revealed significant differences between groups (F(3,20) = 2.93, P = 0.0311). Post hoc analysis revealed significantly lower body mass at the end of the study in the combination exercise plus PA group (25.83 ± 1.72 g) compared to the control group (28.70 ± 1.70 g; p=0.03). Higher soleus mass was found in the mice from the exercise only (11.6 ± 5 mg) and combination exercise plus PA (11.5 ± 3.271 mg) groups compared to the no treatment control group (10.33 ± 3.445 mg), however, these results did not reach significance. No statistical significance was found in the measurement of forelimb or all limb grip strength. CONCLUSION: Our initial hypothesis of synergy was not supported, however, there is preliminary evidence that exercise and PA independently reduces the loss of slow twitch skeletal muscle induced by cancer. Future research is required to validate these results

Effects of a Home-Based Exercise Program on Inflammatory Cytokines and Functional Capacity in Men with Prostate Cancer Under Active Surveillance

Regular exercise can improve physical fitness, functional performance, and quality of life in men with prostate cancer (PCa); however, few men with PCa meet national physical activity guidelines. Structured, home-based exercise programs may bridge this gap and increase physical activity in men with PCa. PURPOSE: This pilot study aimed to investigate the impact of a home-based exercise program on cytokines associated with tumor progression in men with PCa. METHODS: A single group, self-controlled study design was used. Fifteen men with PCa under active surveillance were recruited to complete 24 weeks of a home-based exercise program, combining aerobic and body-weight based exercises. The aerobic portion of the intervention included 5 days of light-to-moderate intensity walking for 30 minutes at 40-60% of the participant’s heart rate reserve as calculated using the Karvonen formula. Body-weight based exercises were performed 3 times per week consisting of 3 sets of 15 reps of bodyweight squats, inclined push-ups, and hip thrusts. Serum was collected at baseline and end of study to measure circulating eotaxin, interferon (IFN)γ, interleukin (IL)-12, IL-1a, IL-5, IL-6, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) cytokines using an 8-protein multiplex (Millipore Sigma, Billerica, MA). A 6-minute walk test (MWT)was completed at the beginning and end of study to measure physical function. T-tests were performed with significance set to p \u3c0.05. RESULTS: A total of 15 men were consented with 9 men completing the intervention (40% attrition due to COVID). At baseline, participants were 70.11 ± 5.42 years of age, weighted 85.31 ± 6.41 kg with a body mass index of 27.77 ± 2.93 kg/m2. A non-significant tendency was observed for improved 6MWT distance (meters) (Pre: 382.7 ± 108.1; Post: 466.7 ± 73.78; p=0.08). Analysis of circulating cytokines showed tendencies for reduced circulating concentrations (pg/mL) of IFNγ (Pre: 152.9 ± 312.7; Post: 118.9 ± 258.8; p=0.08), and VEGF (Pre: 125.2 ± 198.7; Post: 80.29 ± 124.3; p=0.06) following the intervention. Several other biomarkers showed relevant, though not significant, decreases as well, including IL-12 (Pre: 28.69 ± 32.06; Post: 23.92 ± 19.38; -16.6%), IL-1a (Pre: 78.76 ± 183.3; Post: 65.55 ± 147.7; -16.8%), IL-6 (Pre: 23.71 ± 45.64; Post: 21.24 ± 45.18; -10.4%), and TNF-α (Pre: 24.58 ± 35.4; Post: 19.71 ± 20.76; -19.8%). CONCLUSION: Due to institutional COVID-19 protocols limiting in person research visits, six participants declined to continue the study. The small sample size likely accounts for the lack of statistically significant findings. Although the study did not yield statistically significant outcomes, the results of this study show promising indications that a home-based exercise program could be effective in reducing inflammatory cytokines and increasing functional capacity in men with PCa. Further investigation is needed to confirm these results with a powered sample

Impact of a Home-Based Exercise Program on Cardiovascular Disease Biomarkers in Men with Prostate Cancer

Patients with prostate cancer (PCa) tend to live a sedentary lifestyle and fail to meet national physical activity requirements putting them at a greater risk for developing weight-related co-morbidities and cancer recurrence. Physical activity after cancer diagnosis is known to improve body composition, physical function, and overall quality of life. The inclusion of a home-based exercise regimen may increase their physical activity and reduce the risk of weight-related illness. PURPOSE: To gather preliminary data regarding the impact of a home-based exercise program on body composition and cardiovascular disease (CVD) biomarkers. METHODS: A single group self-controlled study design was used to test the hypothesis that a home-based exercise program can reduce CVD risk in men with PCa. Fifteen men with PCa under active surveillance were recruited to complete a 24-week home-based exercise program consisting of both aerobic and strength-based exercises. Each week, participants were asked to complete 5 days of light-to-moderate intensity walking at a heart rate reserve of 40-60% and 3 days of bodyweight-based exercises including 3 sets of 15 reps of squats, incline push-ups, and hip thrusts. Serum was collected at baseline and end of study to quantify circulating CVD biomarkers: a-2 macroglobulin (A2M), C-reactive protein (CRP), fetuin-A, a-1 acid glycoprotein (AGP), fibrinogen, L-selectin, serum amyloid P (SAP), platelet factor 4 (PF4/CXCL4), and adipsin using an 8-protein multiplex (Millipore Sigma, Billerica, MA). T-tests were performed with significance established at pRESULTS: A total of 15 men consented and 9 men saw the trial to completion (Age: 72.0 ± 8.52; Weight: 85.31 ± 6.41 kg; BMI: 27.77 ± 2.93 kg/m2). There was a 40% rate of attrition observed due to COVID-19. No significant changes occurred in average weights and BMI from pre to post trial visits. Though not significant, tendencies for increased concentrations of the anticoagulant, A2M (Pre: 99.83 ± 81.19 pg/mL; Post: 126.7 ± 102.5; p=0.064) and the inflammatory protein, SAP (Pre: 0.63 ± 0.32 pg/mL; Post: 0.86 ± 0.46; p=0.09) were seen. We also observed a 1.5-fold increase in CRP (Pre: 0.47 ± 0.38 pg/mL; Post: 1.19 ± 2.209) perhaps, as a result of an increase in SAP, or indicative of increased levels of stress due to COVID-19. No other significant differences were found. CONCLUSION: The reduced sample size may have contributed to the lack of significance found in the analysis. Although there were no statistically significant findings, the tendencies seen in A2M suggest that a home-based exercise program may protect against certain facets of CVD in this overweight population. However, our enthusiasm is blunted by the observed increases in SAP and CRP. Further investigation is necessary to validate these results

Exercise Does not Stimulate Citrate Synthase Activity in Cachectic Muscle

Cachexia causes metabolic alterations in skeletal muscle mitochondria stimulated by inflammatory imbalance towards pro-inflammatory signaling. Previous work by our group has demonstrated that exercise significantly increases muscle mass in cases of advanced tumors in transgenic mice. Furthermore, we have discovered that the natural product Nexrutine® has anti-inflammatory properties which can be beneficial in protecting mitochondria. PURPOSE: To compare the effects of exercise and Nexrutine® on mitochondrial density in skeletal muscle taken from transgenic adenocarcinoma of the mouse prostate (TRAMP) models. METHODS: This project is a continuation of a larger study investigating the effects of exercise and Nexrutine® on the attenuation of muscle wasting in TRAMP mice. For this analysis, gastrocnemius from 14 TRAMP mice from control (n=5), Nexrutine® (600 mg/kg; n=5), and voluntary wheel running (VWR) groups (n=4) that completed 20 weeks of intervention were used. Mitochondrial activity was quantified using a commercially available citrate synthase assay (Cayman Chemical, USA). An analysis of variance (ANOVA) with Tukey’s post-hoc was performed. Correlations between muscle mass and citrate synthase activity was performed for each group. Alpha was set at p ≤ 0.05. RESULTS: All mice presented with tumors upon necropsy. VWR mice ran on average 6.67 kilometers per day. Nexrutine® group consumed 1.49 mg Nexrutine® per day on average. No significant differences in muscle mass or citrate synthase were observed between groups. Briefly, the control group had 7.31% and 20.75% greater citrate synthase compared to Nexrutine® and exercise groups, respectively. Exercise group was observed to have 35.25% higher than Nexrutine® group. When all samples were combined, a significant positive correlation was observed between muscle mass and citrate synthase (p= 0.04). CONCLUSION: Contrary to our hypothesis, the results suggest neither exercise nor Nexrutine® positively affect citrate synthase activity in cachectic muscle. Future work by our group will focus on reactive oxygen species and mitochondrial complex activity to further understand how cachexia affects skeletal muscle mitochondrial efficiency

Cancer Survivors\u27 Self-Efficacy and Spirituality Outcomes Following a Holistic Integrative Intervention

Cancer treatments often negatively impact health-related quality of life (HR-QOL) for cancer survivors (CS), ignoring the multi-dimensional nature of the human experience of cancer and its impact on mental and spiritual domains. A holistic integrative approach was implemented on a heterogenous population of cancer survivors during the COVID epidemic with the goal of improving their overall well-being by looking beyond physical functioning. PURPOSE: To examine the relationship between spirituality and self-efficacy of cancer survivors of all types of cancer following a holistic intervention during the COVID-19 pandemic. METHODS: Subjects were recruited via network partners and self-referral. Subjects were eligible to participate if they were cancer survivors of any type at any stage of cancer treatment; subjects were ineligible to participate if they presented with any absolute contraindications to exercise testing as per ACSM guidelines. For 16 weeks, subjects were asked to participate in three 75-minute sessions of therapeutic yoga-based with loving kindness meditation per week. Psychosocial support text messages were sent daily to subjects based on their motivational state to encourage participation in these health enhancing behaviors. Data was collected through numerous channels including BlueJay Mobile Telehealth medicine application. RESULTS: A total of 29 survivors provided informed consent. The average age of the subjects was 58.9 years, 25 female survivors and 4 male survivors; 11 of the 29 self-reported as Latino/ Hispanic. The 29 subjects were survivors of the following primary cancers: breast cancer (n=21), cervical cancer (n=2), ovarian cancer (n=1), prostate cancer (n=1), sarcoma (n=1), lymphoma (n=1), thyroid cancer (n=1), or leukemia (n=1). There is a positive association between how confident a cancer survivor feels towards performing exercise in various situations and the amount of social support they receive from their family (p\u3c.001) and friends (p\u3c.001). The individual’s confidence to overcome the obstacle to exercise and their level of hope are associated with the support they receive from loved ones. CONCLUSION: The present study suggests that to improve exercise behavior in adult cancer survivors, one should incorporate social support to strengthen barriers self-efficacy to improve outcome expectations. To further understand these associations, longitudinal research is needed and should include more survivors