WILLIAMS, CHRISTOPHER R.

Abstract Background: The National Comprehensive Cancer Network (NCCN) recommends the use of tissue-based genetic tests, such as Decipher, Prolaris, and Confirm mdx for localized prostate cancer, to help patients and caregivers make more informed treatment decisions at the time of diagnosis. However, while much enthusiasm currently exists for the burgeoning field of genomic medicine, prostate cancer disparities continue to persist in underserved communities despite the existence of evidence-based treatment guidelines. Methods: A diverse 15-member Community Advisory Board (CAB) representing rural and urban communities in Duval County, Florida were recruited from May to June 2023, to build a community-academic partnership, for the development and implementation of a genetic literacy patient-caregiver educational intervention for localized prostate cancer. The 15-member CAB was divided into groups of 5 for focus group discussions. Qualitative and quantitative data from CAB members were integrated to gain better understanding of the facilitators and barriers for prostate cancer genetic literacy in underserved communities. Results: The thematic analysis reveals several key themes related to prostate cancer, screening, treatment, and genetics. These themes reflect the diverse perspectives and experiences of the CAB members regarding prostate cancer, ranging from personal anecdotes to broader societal issues. Participants expressed thoughts related to fear, lack of knowledge, cultural beliefs, and access to healthcare. The discussion on prostate cancer and tissue based genetic testing highlighted the complexities surrounding prostate cancer and the need for further education, awareness, and access to affordable healthcare for all individuals at risk. Conclusion: CAB members emphasized the importance of improving access to information, promoting education, and addressing cultural barriers to ensure that individuals are informed about available options for prostate cancer diagnosis and treatment. Citation Format: Ewan K. Cobran, Jocelyn Turner, Folakemi Odedina, Alan H. Bryce, Christopher Williams, Jose Rodriguez, Roger Williams, Woodrow Nathan, Thomas Bryant III, LoveVonia Nathan, Laureen Husband. Community advisory board members’ perspectives on genetic literacy and patient-caregiver communication of prognostic genomics for localized prostate cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A042.

Anaplasma phagocytophilum is an emerging, Gram-negative, and obligate intracellular pathogen that is infrequently implicated as a causative agent of community-acquired pneumonia. In this paper, we report about an immunocompetent patient from the community who presented with fever, cough, and shortness of breath. Chest X-ray and CT showed bilateral lung infiltrates. Extensive workup for other common and uncommon causes of pneumonia was positive for anaplasmosis. The patient recovered completely with doxycycline therapy. In our literature review, we find that in 80% of reported cases of anaplasmosis pneumonia, empiric treatment did not contain doxycycline, which in some cases led to acute respiratory distress syndrome. Clinicians in tick-borne disease endemic regions should be aware of this unusual presentation of anaplasmosis in order to be able to select appropriate antimicrobial regimens and initiate timely management.

Abstract Bladder cancer is the 4th most commonly diagnosed cancer in the United States. Because superficial bladder cancer (SBC) recurs in about 60% of cases, standard treatment involves tumor resection followed by intravesical therapies to prevent recurrence, as well as lifelong periodic cystoscopy. There is an urgent need for better intravesical therapies to prevent both the recurrence and progression of SBC. The Mammalian Target Of Rapamycin (mTOR) complex is upregulated in many bladder cancer tumors. We have targeted both the mTORc1 and mTORc2 complexes with drugs that inhibit both complexes. We used PP242 and a second inhibitor, OSI-027, which is currently in a phase I clinical trial for solid tumors (NCT00698243). Our in vitro model targets cell proliferation in three bladder cancer cell line (HT1376, T24 and UM-UC-3). Both drugs are effective in inhibiting the growth of bladder cancer cell lines with IC50 values between 0.6 and 18µM. In comparison with rapamycin, both drugs demonstrate effects on downstream targets of both the mTORc1 and mTORc2 pathways including 4EBP1 and pAkt. Receptor tyrosine kinases are another therapeutic target for bladder cancer. Lapatinib which targets EGFR and Her3, in combination with OSI-027 forms a highly synergistic treatment that inhibits bladder cancer cell line growth. Downstream molecular targets of the combination therapy, including the apoptosis markers PARP and caspase 3, were evaluated by Western blots. Our in vitro data suggests that a combination of dual mTOR inhibitors with RTK inhibitors may provide a novel effective therapeutic treatment for bladder cancer. Future studies of the in vivo efficacy of these drug combinations in a mouse model are planned. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 896. doi:1538-7445.AM2012-896

Abstract Bladder cancer is the 5th most commonly diagnosed cancer in the United States. Because superficial bladder cancer (SBC) recurs in about 60% of cases, standard treatment involves tumor resection followed by intravesical therapies to prevent recurrence, as well as lifelong periodic cystoscopy. There is an urgent need for better intravesical therapies to prevent both the recurrence and progression of SBC. Recent evidence has demonstrated that glycogen synthase kinase – 3 beta (GSK3β) plays an important role in pancreatic, ovarian and colon cancers; however, to date the possible role of this important kinase has not been examined in bladder cancer. We propose that GSK3β plays a cancer promoting role in bladder cancer and that inhibition of GSK3β will reduce bladder cancer growth. The GSK3β inhibitor, AR-A014418, has been demonstrated to reduce tumor growth in the previously cited cancers. AR-A014418 reduced cell proliferation of three bladder cancer cell lines (HT1376, T24 and UM-UC-3) with EC50 values of 17.5μM for HT1376, 8μM for T24, and 10μM for UM-UC-3 cells. The effect of AR-A014418 on downstream targets in these cell lines was evaluated by Western blots which indicated an increase in apoptosis in these cells in response to drug treatment as demonstrated by the presence by both PARP and caspase 3 cleavage. The NFkB downstream target XIAP also exhibited reduced protein levels after drug treatment. The HT1376 cell line was transduced with luciferase containing lentivirus particles to generate a luciferase expressing cell line, HT1376-LUC to use for both ectopic and orthotopic models of bladder cancer growth. The efficacy of AR-A014418 in reducing bladder cancer tumor growth was tested in an ectopic mouse model. HT1376-LUC cells mixed with matrigel were transplanted into the right flank of 50 female nude mice. After one week, mice containing tumors with an average volume of 52 mm3 were randomized into four treatment groups of 10 mice each. Mice were treated twice weekly via IP injection with placebo, 1, 5 or 7mg/kg AR-A014418. Tumor sizes were measured and imaged for luciferase activity once weekly. Tumor growth was inhibited by both 5mg/kg and 7mg/kg doses by 19 days of treatment (p < 0.05, Student's T test). Together, the in vitro and in vivo data suggest that GSK3β is a novel target for bladder cancer treatment. Future studies using an orthotopic model of bladder cancer are planned. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1671. doi:10.1158/1538-7445.AM2011-1671