Expanding Outcomes in Cancer Screening Safety Net Programs: Promoting Sustainability and Policy Reform.

Community-engaged patient navigation safety net programs are established as an evidence-based approach to address cancer prevention and early detection efforts, but barriers to expand and sustain such programs persist. In addition, few studies describe how these programs impact buy-in among communities and policy change within health care systems and government. We describe how we used the Capacity for Sustainability Framework to guide efforts for program sustainability and community, institutional, and policy level change in a breast cancer screening and patient navigation safety net program. The nine domains of the Capacity for Sustainability Framework were used to develop program logic models, to inform program implementation and quality improvement agendas, and to guide multi-level partner and stakeholder engagement, outreach, and dissemination of outcomes. The program is currently in its seventh year and continues to be annually funded by a city public health department. In 2021, additional 5-year renewable funding from a state public health department was secured. In addition, institutional program support was expanded for patients diagnosed with breast cancer. Program leaders worked with policymakers to draft legislation to support training certification and third-payor reimbursement for patient navigators and community health workers. The program is well-known and trusted among community members, community-based organizations, and providers. Community, organizational, and policy-level outcomes demonstrate that community-engaged patient navigation safety net programs can influence more than individual and interpersonal outcomes and can be sustained over time.

Creating and Implementing a Community Engagement Strategy for the 2022-2027 Illinois Comprehensive Cancer Control Plan Through an Academic-State Public Health Department Partnership.

INTRODUCTION: Comprehensive cancer control (CCC) plans are state-level blueprints that identify regional cancer priorities and health equity strategies. Coalitions are encouraged to engage with community members, advocacy groups, people representing multiple sectors, and working partners throughout the development process. We describe the community and legislative engagement strategy developed and implemented during 2020-2022 for the 2022-2027 Illinois CCC plan. METHODS: The engagement strategies were grounded in theory and evidence-based tools and resources. It was developed and implemented by coalition members representing the state health department and an academic partner, with feedback from the larger coalition. The strategy included a statewide town hall, 8 focus groups, and raising awareness of the plan among state policy makers. RESULTS: A total of 112 people participated in the town hall and focus groups, including 40 (36%) cancer survivors, 31 (28%) cancer caregivers, and 18 (16%) Latino and 26 (23%) African American residents. Fourteen of 53 (26%) focus group participants identified as rural. Participants identified drivers of cancer disparities (eg, lack of a comprehensive health insurance system, discrimination, transportation access) and funding and policy priorities. Illinois House Resolution 0675, the Illinois Cancer Control Plan, was passed in March 2022. CONCLUSION: The expertise and voices of community members affected by cancer can be documented and reflected in CCC plans. CCC plans can be brought to the attention of policy makers. Other coalitions working on state plans may consider replicating our strategy. Ultimately, CCC plans should reflect health equity principles and prioritize eliminating cancer disparities.

MC1R variants and associations with pigmentation characteristics and genetic ancestry in a Hispanic, predominately Puerto Rican, population.

Skin cancer risk information based on melanocortin-1 receptor (MC1R) variants could inform prevention and screening recommendations for Hispanics, but limited evidence exists on the impact of MC1R variants in Hispanic populations. We studied Hispanic subjects, predominately of Puerto Rican heritage, from Tampa, Florida, US, and Ponce, PR. Blood or saliva samples were collected by prospective recruitment or retrieved from biobanks for genotyping of MC1R variants and ancestry informative markers. Participant demographic and self-reported phenotypic information was collected via biobank records or questionnaires. We determined associations of MC1R genetic risk categories and phenotypic variables and genetic ancestry. Over half of participants carried MC1R variants known to increase risk of skin cancer, and there was diversity in the observed variants across sample populations. Associations between MC1R genetic risk groups and some pigmentation characteristics were identified. Among Puerto Ricans, the proportion of participants carrying MC1R variants imparting elevated skin cancer risk was consistent across quartiles of European, African, and Native American genetic ancestry. These findings demonstrate that MC1R variants are important for pigmentation characteristics in Hispanics and that carriage of high risk MC1R alleles occurs even among Hispanics with stronger African or Native American genetic ancestry.

Arbuscular mycorrhizal symbiosis increases the content of volatile terpenes and plant performance in Satureja macrostema (Benth. ) Briq / La simbiosis micorrícica arbuscular aumenta el contenido de terpenos volátiles y el rendimiento vegetal en Satureja macrostema (Benth.) Briq

We studied the effect of Rhizophagus irregularis on plant performance and volatile terpenes content of the Mexican native medicinal plant Satureja macrostema (Benth.) Briq. (Lamiaceae) in greenhouse conditions. The growth parameters considered in this research and the composition of volatile components were quantified monthly in mycorrhizal and non-mycorrhizal plants. The essential oil was collected from aerial parts and analyzed by gas chromatography-mass spectrometry. Colonization by R. irregularis significantly increased biomass, shoot and root length, and the amount of volatile terpenes. The more concentrated volatile terpenes were limonene, β- linalool, menthone, pulegone, and verbenol acetate. It is concluded that the use of R. irregularis allows optimal growth of S. macrostema plants in low fertility soils and increased production of the main components of the essential oil.

El efecto de Rhizophagus irregularis sobre el rendimiento vegetal y la producción de los terpenos volátiles de Satureja macrostema (Benth.) Briq. (Lamiaceae), una planta medicinal nativa mexicana, fue estudiado en condiciones de invernadero. Los parámetros de crecimiento considerados en esta investigación y los componentes volátiles, fueron cuantificados mensualmente en plantas con y sin micorrizas. El aceite esencial fue colectado de la parte aérea y fue analizado por técnicas de cromatografía de gases-espectrometría de masas. La colonización de R. irregularis aumentó significativamente la biomasa, longitud de tallo y raíz, y la cantidad de terpenos volátiles. Los terpenos volátiles mayoritarios fueron limoneno, β-linalol, mentona, pulegona y acetato de verbenol. Se concluye que el uso de R. irregularis permitió un óptimo crecimiento de las plantas de S. macrostema en suelos de baja fertilidad, con un aumento de los componentes principales del aceite esencial.

Anti-tumor and immunomodulatory activity of resveratrol in vitro and its potential for combining with cancer immunotherapy.

We evaluated the anti-tumor effect of Resveratrol (RV) on M21 and NXS2 tumor cell lines and its immunosuppressive activity on human and murine immune cells to determine the potential for combining RV and immunotherapy. In vitro, concentrations of RV≥25 mcM, inhibited cell proliferation, blocked DNA synthesis and induced G1 phase arrest in tumor and immune cells. RV at 12-50 mcM inhibited antibody dependent cell mediated cytotoxicity (ADCC) of tumor cells facilitated by the hu14.18-IL2 immunocytokine (IC). The in vivo anti-tumor and immunomodulating activity of RV given systemically were assessed in mice. Results showed that this RV regimen inhibited the growth of NXS2 tumors in vivo but did not appear to interfere with blood cell count, splenocyte or macrophage function. Thus, RV may be a candidate for combining with immunotherapy.

The anti-tumor effect of resveratrol alone or in combination with immunotherapy in a neuroblastoma model.

We investigated the anti-tumor effect of peritumoral resveratrol in combination with immunotherapy in vivo in neuroblastoma-bearing mice. Subcutaneous NXS2 tumors were induced in A/J mice. On day 10, some mice received 15 mcg of intravenous immunocytokine for 5 days, mice received 20 mg of peritumoral resveratrol twice a week (starting on day 12) for a total of 5 injections, and a separate group received a combination of both regimens. Tumor progression and survival were assessed every 3-4 days. Blood and primary tumor tissue samples were collected on day 20 for Complete Blood Count and CD45 immunohistochemistry and histology, respectively. The primary tumor regressed in all mice receiving peritumoral resveratrol. Most of these mice receiving peritumoral resveratrol alone developed metastatic tumors and recurrence of the primary tumor after cessation of therapy. When resveratrol and immunocytokine regimens were combined, 61% of the mice receiving this combination therapy resolved their primary tumors and survived without developing metastatic tumors, compared to 15 and 13% receiving resveratrol or immunocytokine alone, respectively. None of the therapeutic regimes prevented lymphocyte infiltration or affected the complete blood count. Greater necrosis was observed microscopically in tumors from mice receiving the combination therapy. These results demonstrate that the combination therapy of peritumoral resveratrol plus intravenous immunocytokine provides better anti-tumor effects in this model than either therapy alone.

A second-site suppressor significantly improves the defective phenotype imposed by mutation of an aromatic residue in the N-terminal domain of the HIV-1 capsid protein.

The HIV-1 capsid (CA) protein plays an important role in virus assembly and infectivity. Previously, we showed that Ala substitutions in the N-terminal residues Trp23 and Phe40 cause a severely defective phenotype. In searching for mutations at these positions that result in a non-lethal phenotype, we identified one candidate, W23F. Mutant virions contained aberrant cores, but unlike W23A, also displayed some infectivity in a single-round replication assay and delayed replication kinetics in MT-4 cells. Following long-term passage in MT-4 cells, two second-site mutations were isolated. In particular, the W23F/V26I mutation partially restored the wild-type phenotype, including production of particles with conical cores and wild-type replication kinetics in MT-4 cells. A structural model is proposed to explain the suppressor phenotype. These findings describe a novel occurrence, namely suppression of a mutation in a hydrophobic residue that is critical for maintaining the structural integrity of CA and proper core assembly.