Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE2 face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic. This article compared the three methods to identify the best platform for training URM students in cancer disparity research. The program's effectiveness was measured through motivation, experiences, and knowledge gained by trainees during and one year after the completion of the program. The results showed that the participants were highly positive in their feedback about the professional and academic values of the program. Although the virtual and hybrid methods experienced significant challenges during the pandemic, the hybrid training module offered an "above average" effectiveness in performance, like the face-to-face mentoring platform in mentoring URM students in cancer disparity research.

Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes.

INTRODUCTION: The Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE2 triad partnership. METHODS: CaRE2 serves diverse populations in Florida and California using a "molecule to the community and back" model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. RESULTS: Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE2-related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. CONCLUSION: The CaRE2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

Thymoquinone Inhibition of Chemokines in TNF-α-Induced Inflammatory and Metastatic Effects in Triple-Negative Breast Cancer Cells.

The lack of identifiable molecular targets or biomarkers hinders the development of treatment options in triple-negative breast cancer (TNBC). However, natural products offer a promising alternative by targeting inflammatory chemokines in the tumor microenvironment (TME). Chemokines are crucial in promoting breast cancer growth and metastasis and correlate to the altered inflammatory process. In the present study, we evaluated the anti-inflammatory and antimetastatic effects of the natural product thymoquinone (TQ) on TNF-α-stimulated TNBC cells (MDA-MB-231 and MDA-MB-468) to study the cytotoxic, antiproliferative, anticolony, antimigratory, and antichemokine effects using enzyme-linked immunosorbent assays, quantitative real-time reverse transcription-polymerase chain reactions, and Western blots were used in sequence to validate the microarray results further. Four downregulated inflammatory cytokines were identified, CCL2 and CCL20 in MDA-MB-468 cells and CCL3 and CCL4 in MDA-MB-231 cells. Furthermore, when TNF-α-stimulated MDA-MB-231 cells were compared with MDA-MB-468 cells, the two cells were sensitive to TQ's antichemokine and antimetastatic effect in preventing cell migration. It was concluded from this investigation that genetically different cell lines may respond to TQ differently, as TQ targets CCL3 and CCL4 in MDA-MB-231 cells and CCL2 and CCL20 in MDA-MB-468 cells. Therefore, the results indicate that TQ may be recommended as a component of the therapeutic strategy for TNBC treatment. These outcomes stem from the compound's capacity to suppress the chemokine. Even though these findings support the usage of TQ as part of a therapy strategy for TNBC associated with the identified chemokine dysregulations, additional in vivo studies are needed to confirm these in vitro results.

Design and Synthesis of New Acyl Urea Analogs as Potential σ1R Ligands.

In search of synthetically accessible open-ring analogs of PD144418 or 5-(1-propyl-1,2,5,6-tetrahydropyridin-3-yl)-3-(p-tolyl)isoxazole, a highly potent sigma-1 receptor (σ1R) ligand, we herein report the design and synthesis of sixteen arylated acyl urea derivatives. Design aspects included modeling the target compounds for drug-likeness, docking at σ1R crystal structure 5HK1, and contrasting the lower energy molecular conformers with that of the receptor-embedded PD144418-a molecule we opined that our compounds could mimic pharmacologically. Synthesis of our acyl urea target compounds was achieved in two facile steps which involved first generating the N-(phenoxycarbonyl) benzamide intermediate and then coupling it with the appropriate amines weakly to strongly nucleophilic amines. Two potential leads (compounds 10 and 12, with respective in vitro σ1R binding affinities of 2.18 and 9.54 µM) emerged from this series. These leads will undergo further structure optimization with the ultimate goal of developing novel σ1R ligands for testing in neurodegeneration models of Alzheimer's disease (AD).

Improving Representation of Underrepresented Minority (URM) Students in Oncology Biomedical Research Workforce: Outcome Evaluation from the ReTOOL Program.

The Research Training Opportunities for Outstanding Leaders (ReTOOL) program was implemented in 2012 to increase the representation of racial and ethnic minorities in the biomedical workforce. Specifically, the ReTOOL program aims to foster the capacity for scientific research among underserved populations as well as address the cultural appropriateness of research projects. This paper describes the impact of the ReTOOL program in enhancing the research training of underrepresented minority (URM) students. Forty URM students who completed the ReTOOL program between 2012 and 2019 were invited to participate in the program evaluation. The response rate was 73% with 29 participants. Of the 29 participants, 26 trainees self-identified as Black or African-American. A structured survey developed for the program was employed for data collection, using a Likert Scale ranging from 1 to 5, with 5 being the best. The item ratings ranged from 4.45 to 4.80. Responses to open-ended questions show that ReTOOL has been instrumental in socializing and acculturating participants into the habits of scientific thinking. The combined use of quantitative and qualitative inquiry depicts that ReTOOL has been highly successful in fostering participant enrollment in advanced health-related or professional degree programs.

Developing a Novel Framework for an Undergraduate Cancer Research Education and Engagement Program for Underrepresented Minority Students: the Florida-California CaRE2 Research Education Core (REC) Training Program.

Lack of substantive research experiences and technical skills mentoring during undergraduate studies leaves many underrepresented minority (URM) students unprepared to apply to competitive graduate programs. As a part of our ongoing effort to increase the pipeline for the development and training of successful URM scientists in biomedical sciences with focus on reducing cancer health disparities, the Florida-California Cancer Research Education and Engagement (CaRE2) Health Equity Center was launched in 2018. Funded through an NIH/NCI U54 grant mechanism, the CaRE2 Center is a triad partnership among Florida Agricultural and Mechanical University (FAMU), a minority-serving institution, University of Florida (UF), and University of Southern California (USC) Cancer Center. One of the objectives of the triad partnership is to promote the coordination and implementation of the training of the next generation of Black and Latinx biomedical scientists in Florida and California. An important component of the CaRE2 program is the Research and Education Core (REC) designed to coordinate the training of URM students and researchers at different levels in their academic and professional developments. The undergraduate cancer research training program under FAMU-CaRE2 Center is a 3-year (2018-2021) project to identify, train, mentor, and provide the URM undergraduate students with the support network they need to flourish in the program and beyond. In its year-1 funding cycle, the program has made significant progress in developing a novel framework for an undergraduate cancer research education and engagement program at FAMU, one of the forefront minority institutions in the nation. The mentored research program is complemented with professional development and engagement activities, including cancer research seminars, workshops, and community outreach activities. The purpose of this paper is to discuss the strategies implemented for an effective partnership, the leadership and mentoring skills, and outcomes from the year-1 experiences. In addition, we present the progress made in advancing the pool of underrepresented minority students with scientific and academic career progression paths focused on cancer health disparities.

Design and evaluation of novel oxadiazole derivatives as potential prostate cancer agents.

Various 1,3,4-oxadiazole derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cell lines. Most of the compounds showed promising activity. Among them, compounds 2d (IC50=0.22 and 1.3µM) and 2a (IC50=8.34 and 2,5µM) have shown significant activities on PC-3 and LNCaP cell lines respectively. To investigate the mechanism of cell death we performed cell apoptosis staining and cell cycle arrest assay on more sensitive PC-3 cell lines on 2d. The results demonstrated that 2d induced apoptosis and shifted the cells to the sub G0/G1 and S phase. Our study evidently identified the potency of compound 2d as potential anti-prostate cancer agent.

Synthesis and Cytotoxic Evaluation of Pyrrole Hetarylazoles Containing Benzimidazole/Pyrazolone/1,3,4-Oxadiazole Motifs.

Azomethine linked pyrrole bishetarylazoles containing benzimidazole/pyrazolone/1,3,4-oxadiazole were synthesized in satisfactory yields. Their structures were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Evaluation for the cytotoxic activities In vitro against a panel of breast cancer cell lines (MDA-AB-231, BT-474 and Ishikawa cells) revealed that the pyrrole-benzimidazole hybrids are more potent than the pyrazolone and 1,3,4-oxadiazole hybrids in all cell lines. Compound (9) displayed promising cytotoxicity against BT-474 cell line with IC50 values, 7.7 µM.

Application of Machine Learning Algorithms in Breast Cancer Diagnosis and Classification.

Breast cancer continues to be the most frequent cancer in females, affecting about one in 8 women and causing the highest number of cancer-related deaths in females worldwide despite remarkable progress in early diagnosis, screening, and patient management. All breast lesions are not malignant, and all the benign lesions do not progress to cancer. However, the accuracy of diagnosis can be increased by a combination or preoperative tests such as physical examination, mammography, fine-needle aspiration cytology, and core needle biopsy. Despite some limitations, these procedures are more accurate, reliable, and acceptable, when compared with a single adopted diagnostic procedure. Recent studies have shown that breast cancer can be accurately predicted and diagnosed using machine learning (ML) technology. The objective of this study was to explore the application of ML approaches to classify breast cancer based on feature values generated from a digitized image of a fine-needle aspiration (FNA) of a breast mass. To achieve this objective, we used ML algorithms, collected a scientific dataset of 569 breast cancer patients from Kaggle (https://www.kaggle.com/uciml/breast-cancer-wisconsin-data), analyze and interpreted the data based on ten real-valued features of a breast mass FNA including the radius, texture, perimeter, area, smoothness, compactness, concavity, concave points, symmetry, and fractal dimension. Among the 569 patients tested, 63% were diagnosed with benign breast cancer and 37% were diagnosed with malignant breast cancer. Benign tumors grow slowly and do not spread while malignant tumors grow rapidly and spread to other parts of the body.

Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment.

To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system. Various cellular components of the TME work together to drive cancer processes, some of which include tumor-associated adipocytes, fibroblasts, macrophages, and neutrophils which sustain perpetual amplification and release of pro-inflammatory molecules such as cytokines. Thymoquinone (TQ), a natural chemical component from black cumin seed, is widely used traditionally and now in clinical trials for the treatment/prevention of multiple types of cancer, showing a potential to mitigate components of TME at various stages by various pathways. In this review, we focus on the role of TME in TNBC cancer progression and the effect of TQ on the TME, emphasizing their anticipated role in the prevention and treatment of TNBC. It was concluded from this review that the multiple components of the TME serve as a critical part of TNBC tumor promotion and stimulation of uncontrolled cell proliferation. Meanwhile, TQ could be a crucial compound in the prevention and progression of TNBC therapy through the modulation of the TME.

N-(4-amino-7-nitrobenzaoxa-1,3-diazole)-substituted aza crown ethers: complexation with alkali, alkaline earth metal ions and ammonium.

Three novel aza-crown ether derivatives incorporating 4-amino-7-nitrobenzaoxa-1,3-diazole (NBD) chromophore were synthesized and their structure confirmed by (1)H-NMR, IR and elemental analysis. The influence of the solvent polarity and protonation on the photophysical properties of NBD-15-crown-5 was studied by UV/Vis and fluorescence methods. The influence of the investigated cations on the absorption spectra of the ligands was negligible, however emission was strongly affected. Complexation and binding stability of NBD-aza-15-crown-5 and NBD-aza-18-crown-6 were studied using fluorescence spectroscopy. NBD-aza-18-crown-6 exhibits strong selectivity toward Ca(2+) and Sr(2+) ions with formation constants about 10(3) times higher than the formation constants with the other ions included in the study.

Synthesis of 2-(N-Benzylpyrrolyl)-benzimidazoles Using Polyphosphoric Acid Prompted Cyclocondensation.

Synthesis of a series of 2-substituted benzimidazoles was carried out for screening anti-inflammatory activities. 2-(N-benzylpyrrolyl)-benzimidazoles 9a-k were synthesized from N-benzyl-2-pyrrole carboxylic acids 8a-d and 4-substituted-1,2-phenylenediamines by cyclocondensation utilizing polyphosphoric acid (PPA) as condensing agent. The N-benzyl-2-pyrrole carboxylic acids were prepared by standard method of N-benzylation of 2-pyrrole carboxylate using NaH/DMF and appropriately substituted benzyl halides followed by alkaline hydrolysis.

Synthesis and Biological Evaluations of Ring Substituted Tetrahydroisoquinolines (THIQs) as Anti-Breast Cancer Agents.

Breast cancer is a leading cause of mortality among women, resulting in more than half a million deaths worldwide every year. Although chemotherapeutic drugs remain the main stay of cancer treatment, it is observed that toxicity to normal cells poses a limitation to their therapeutic values. Moreover, the patient recovery rate from advanced breast cancer by chemotherapy is still unacceptably low. Tetrahydroisoqinoline derivatives (THIQs) were reported to act as selective subtype estrogen receptor antagonists/agonists and may serve as potential therapeutic agents for breast cancer. In continuation of previous work we systematically synthesized and characterized the tetrahydroisoquinoline (THIQs) analogs. In-vitro antiproliferative activity of new substituted tetrahydroisoquinoline analogs were evaluated against human ER (+) MCF-7 (breast), ER (-) MDA-MB-231 (breast) and Ishikawa (endometrial) cancer cell lines using the CellTiter-Glo luminescent cell viability assay. The most active compounds obtained in this study were 2b, 2i, and 3 g as demonstrated by their activity (IC50=0.2 µg/mL, 0.08 µg/mL; 0.61 µg/mL, 0.09 µg/mL; 0.25 µg/mL, 0.11 µg/mL) against MCF-7 and Ishikawa cell lines respectively, in comparison to Tamoxifen activity (IC50=3.99 µg/mL, 7.87 µg/ml). The newly synthesized molecules were docked in the active sites of the ER-α (PDB: 3ERT), ER-ß (PDB: 1QKN) and alpha-beta tubulin taxol complex (1JFF) crystal structures to determine the probable binding modes (bioactive conformations) of the active compounds.

4,5-Dimethoxy-2-nitrobenzohydrazides and 1-(1-Benzylpiperidin-4-yl)ethan-1-ones as Potential Antioxidant/Cholinergic Endowed Small Molecule Leads.

The objective of this research is to generate leads for developing our ultimate poly-active molecules with utility in central nervous system (CNS) diseases. Indeed, poly-active molecules capable of mitigating brain free radical damage while enhancing acetylcholine signaling (via cholinesterase inhibition) are still being sought for combating Alzheimer's disease (AD). We differentiate "poly-active" agents from "multi-target" ones by defining them as single molecular entities designed to target only specific contributory synergistic pharmacologies in a disease. For instance, in AD, free radicals either initiate or act in synergy with other pharmacologies, leading to disease worsening. For this preliminary report, a total of 14 (i.e., 4,5-dimethoxy-2-nitrobenzohydrazide plus 1-(1-benzylpiperidin-4-yl)ethan-1-one) derivatives were synthesized and screened, in silico and in vitro, for their ability to scavenge free radicals and inhibit acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) enzymes. Overall, six derivatives (4a, 4d, 4e, 4f, 4g, 9b) exhibited potent (>30%) antioxidant properties in the oxygen radical absorbance capacity (ORAC) assay. The antioxidant values were either comparable or more potent than the comparator molecules (ascorbic acid, resveratrol, and trolox). Only three compounds (4d, 9a, 9c) yielded modest AChE/BuChE inhibitions (>10%). Please note that a SciFinder substance data base search confirmed that most of the compounds reported herein are new, except 9a and 9c which are also commercially available.

Synthesis, characterization, and electrospinning of novel polyaniline-peptide polymers.

Aniline-peptide (FLDQV, FLDQVC, Dansyl-FLDQV, Dansyl-FLDQVC, and FLDQV-AMC) mixtures underwent oxidative chemical and electrochemical polymerization in excess of aniline. The products of the chemical polymerization were low molecular weight polymers containing more than 70% peptide. Electrochemically polymerized species polyaniline-FLDQV (PANI-FLDQV) consisted mainly of polyaniline units containing about 10% peptide. The solubility of the latter in 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) was similar to the camphorsulfonic acid (CSA) doped emeraldine base (PANI-CSA) solubility, however the weight composition of the electrospun fibers produced from the two polymers was significantly different. 2D 1H-13C HSQC analyses were employed to analyze the binding between the aniline and peptide moieties. Binding of peptide to polyaniline is reflected by the appearance of extra cross-peaks which display line broadening between the free polyaniline and the free pentapeptide. Peptides may be chemically bonded to the polymer molecules, but they may also act as doping agents to the nitrogen atoms via hydrogen bonding.

Synthesis of Some Benzimidazole Derivatives Bearing 1,3,4-Oxadiazole Moiety as Anticancer Agents.

In an effort to establish new benzimidazole related structural leads with improved anticancer activity, several new benzimidazole derivatives (5a-i) with 1,3,4-oxadiazole scaffold incorporated were synthesized and studied for their anticancer activity. The anticancer screening against MDA-MB-231 breast cancer cell lines showed that compound (5c) exhibited moderate cytotoxicity.

Dansyl - Substituted Aza Crown Ethers: Complexation with Alkali, Alkaline Earth Metal Ions and Ammonium.

The present study investigates the binding properties of four dansyl substituted aza-crown ethers with alkali, alkaline earth metal ions and ammonium. The influence of the solvent polarity and protonation on the photophysical properties of the compounds was studied by UV/Vis and fluorescence methods. The host species caused only slight changes on the absorption spectra of the ligands. The fluorescence changes were more pronounced and concentration dependent thus allowing to calculate the binding constants of the process. The most stable complex under our working conditions was the one between Ba(2+) and DNS18C6.