Evolution of the joint International Atomic Energy Agency (IAEA), International Agency for Research on Cancer (IARC), and WHO cancer control assessments (imPACT Reviews).

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum.

Situational analysis of breast health care systems: Why context matters.

BACKGROUND: Implementation of evidence-based, resource-appropriate guidelines for breast cancer control should be preceded by a baseline assessment or situational analysis to assess breast health infrastructure, workforce capacity, patient pathways, existing practices, accessibility, and costs. METHODS: To support the assessment of breast health care systems within the broader context in which they exist, the Breast Health Global Initiative (BHGI) developed, tested, and refined a set of situational analysis tools with which to guide the assessment of breast health care capacity, identify the relative strengths and weaknesses of the health system, and support stakeholders in prioritizing actionable items to advance breast cancer care using evidence-based strategies tailored to their setting. The tools address 6 domains of breast health care delivery: 1) breast cancer early detection practices; 2) breast cancer awareness programs; 3) the availability of breast cancer surgery; 4) the availability of pathology; 5) the availability of radiotherapy, and 6) the availability of systemic therapy services. The current study also describes the more comprehensive International Atomic Energy Agency Programme of Action for Cancer Therapy (PACT) integrated missions for PACT (imPACT) review. RESULTS: As of 2020, 5 formal BHGI situational analyses have been performed in India, Brazil, Panama, Tanzania, and Uganda. As of August 2019, a total of 100 imPACT reviews have been conducted in 91 countries. These assessments can contribute to more informed policymaking. CONCLUSIONS: Situational analyses are a prerequisite for the development of resource-appropriate strategies with which to advance breast cancer control in any setting and should assess services across the entire breast health care continuum as well as the broader structural, sociocultural, personal, and financial contexts within which they operate.

A low-passage insect-cell isolate of bluetongue virus uses a macropinocytosis-like entry pathway to infect natural target cells derived from the bovine host.

Bluetongue virus (BTV) causes an economically important disease in domestic and wildlife ruminants and is transmitted by Culicoides biting midges. In ruminants, BTV has a wide cell tropism that includes endothelial cells of vascular and lymphatic vessels as important cell targets for virus replication, and several cell types of the immune system including monocytes, macrophages and dendritic cells. Thus, cell-entry represents a particular challenge for BTV as it infects many different cell types in widely diverse vertebrate and invertebrate hosts. Improved understanding of BTV cell-entry could lead to novel antiviral approaches that can block virus transmission from cell to cell between its invertebrate and vertebrate hosts. Here, we have investigated BTV cell-entry using endothelial cells derived from the natural bovine host (BFA cells) and purified whole virus particles of a low-passage, insect-cell isolate of a virulent strain of BTV-1. Our results show that the main entry pathway for infection of BFA cells is dependent on actin and dynamin, and shares certain characteristics with macropinocytosis. The ability to use a macropinocytosis-like entry route could explain the diverse cell tropism of BTV and contribute to the efficiency of transmission between vertebrate and invertebrate hosts.

Ten Years of the International Cancer Control Partnership: Promoting National Cancer Control Plans to Shape the Health System Response for Cancer Control.

Growing premature mortality because of cancer is an increasing public health concern in all countries. This article reviews 10 years of the International Cancer Control Partnership (ICCP) considering the themes of National Cancer Control Plan (NCCP) support, technical assistance, governance, and the renewed momentum of global calls to action. ICCP has provided key resources for the cancer community by hosting a portal with national cancer control and noncommunicable disease (NCD) plans, strategies, guidelines, and key implementation guides for a growing community of best practices. ICCP partners have responded to the changing needs of country planners, adjusting technical guidance as needs evolve from planning to implementation at the national level with an associated shift to peer-to-peer learning and knowledge exchange. The ICCP offer to assist countries in cancer planning continues to be relevant as countries focus on implementation of global initiatives for breast, cervical, and childhood cancers. These initiatives are important to drive priority actions and a systems approach in the emerging road map on NCDs-a message that will be supported by a second global review of NCCPs in 2023. This is critical for driving national action in all countries on cancer and other NCDs in line with global health commitments made for 2030 and adopted by the United Nations General Assemblies. ICCP sees robust systems and financial planning for implementation, monitoring, and evaluation of NCCPs and protection from cancer-related catastrophic expenditure, as critical to longer-term sustainability and success. ICCP calls for national policymakers to prioritize integration of cancer prevention and control into emerging universal health care approaches, including pandemic preparedness/health system resilience and calls for an equity focus in new NCCPs.

Radiotherapy prioritization in 143 national cancer control plans: Correlation with radiotherapy machine availability, geography and income level.

BACKGROUND: In 2015, the Global Task Force on Radiotherapy for Cancer Control (GTFRCC) called for 80% of National Cancer Control Plans (NCCP) to include radiotherapy by 2020. As part of the ongoing ESTRO Global Impact of Radiotherapy in Oncology (GIRO) project, we assessed whether inclusion of radiotherapy in NCCPs correlates with radiotherapy machine availability, national income, and geographic region. METHODS: A previously validated checklist was used to determine whether radiotherapy was included in each country's NCCP. We applied the CCORE optimal radiotherapy utilisation model to the GLOBOCAN 2020 data to estimate the demand for radiotherapy and compared this to the International Atomic Energy Agency (IAEA) Directory of Radiotherapy Centres (DIRAC) supply data, stratifying by income level and world region. World regions were defined according to the IAEA. FINDINGS: Complete data (including GLOBOCAN 2020, DIRAC and NCCP) was available for 143 countries. Over half (55%, n = 79) included a radiotherapy-specific checklist item within the plan. Countries which included radiotherapy services planning in their NCCP had a higher median number of machines (1.68 vs 0.75 machines/1000 patients needing radiotherapy, p < 0.001). There was significant regional and income-level heterogeneity in the inclusion of radiotherapy-related items in NCCPs. Low-income and Asia-Pacific countries were least likely to include radiation oncology services planning in their NCCP (p = 0.06 and p = 0.003, respectively). Few countries in the Asia-Pacific (18.6%) had a plan to develop or maintain radiation services, compared to 57% of countries in Europe. INTERPRETATION: Only 55% of current NCCPs included any information regarding radiotherapy, below the GTFRCC's target of 80%. Prioritisation of radiotherapy in NCCPs was correlated with radiotherapy machine availability. There was regional and income-level heterogeneity regarding the inclusion of specific radiotherapy checklist items in the NCCPs. Ongoing efforts are needed to promote the inclusion of radiotherapy in future iterations of NCCPs in order to improve global access to radiation treatment. FUNDING: No direct funding was used in this research.

High-dose Mycobacterium tuberculosis aerosol challenge cannot overcome BCG-induced protection in Chinese origin cynomolgus macaques; implications of natural resistance for vaccine evaluation.

This study describes the use of cynomolgus macaques of Chinese origin (CCM) to evaluate the efficacy and immunogenicity of the BCG vaccine against high dose aerosol Mycobacterium tuberculosis challenge. Progressive disease developed in three of the unvaccinated animals within 10 weeks of challenge, whereas all six vaccinated animals controlled disease for 26 weeks. Three unvaccinated animals limited disease progression, highlighting the intrinsic ability of this macaque species to control disease in comparison to macaques of other species and genotypes. Low levels of IFNγ were induced by BCG vaccination in CCM suggesting that IFNγ alone does not provide a sufficiently sensitive biomarker of vaccination in this model. An early response after challenge, together with the natural bias towards terminal effector memory T-cell populations and the contribution of monocytes appears to enhance the ability of CCM to naturally control infection. The high dose aerosol challenge model of CCM has value for examination of the host immune system to characterise control of infection which would influence future vaccine design. Although it may not be the preferred platform for the assessment of prophylactic vaccine candidates, the model could be well suited for testing post-exposure vaccination strategies and drug evaluation studies.

Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus.

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV.

Characterization of the Myeloid Cell Populations' Resident in the Porcine Palatine Tonsil.

The palatine tonsil is the portal of entry for food and air and is continuously subjected to environmental challenges, including pathogens, which use the tonsil and pharynx as a primary site of replication. In pigs, this includes the viruses causing porcine respiratory and reproductive syndrome, and classical and African swine fever; diseases that have impacted the pig production industry globally. Despite the importance of tonsils in host defense, little is known regarding the phenotype of the myeloid cells resident in the porcine tonsil. Here, we have characterized five myeloid cell populations that align to orthologous populations defined in other mammalian species: a CD4+ plasmacytoid dendritic cell (DC) defined by expression of the conserved markers E2.2 and IRF-7, a conventional dendritic cell (cDC1) population expressing CADM1highCD172alow and high levels of XCR1 able to activate allogeneic CD4 and CD8 T cells; a cDC2 population of CADM1dim cells expressing FLT3, IRF4, and CSF1R with an ability to activate allogeneic CD4 T cells; CD163+ macrophages (MÏ´s) defined by high levels of endocytosis and responsiveness to LPS and finally a CD14+ population likely derived from the myelomonocytic lineage, which showed the highest levels of endocytosis, a capacity for activation of CD4+ memory T cells, combined with lower relative expression of FLT3. Increased knowledge regarding the phenotypic and functional properties of myeloid cells resident in porcine tonsil will enable these cells to be targeted for future vaccination strategies to current and emerging porcine viruses.

Perspectives on Strengthening Cancer Research and Control in Latin America Through Partnerships and Diplomacy: Experience of the National Cancer Institute's Center for Global Health.

According to the Pan American Health Organization, noncommunicable diseases, including cancer, are the leading causes of preventable and premature death in the Americas. Governments and health care systems in Latin America face numerous challenges as a result of increasing morbidity and mortality from cancer. Multiple international organizations have recognized the need for collaborative action on and technical support for cancer research and control in Latin America. The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one entity among many that are working in the region and has sought to develop a strategy for working in Latin America that draws on and expands the collaborative potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward developing and implementing initiatives in collaboration with global partners that share the common objectives of building a global cancer research community and translating research results into evidence-informed policy and practice. Both objectives are complementary and synergistic and are additionally supported by an overarching strategic framework that is focused on partnerships and science diplomacy. This work highlights the overall strategy for NCI-CGH engagement in Latin America through partnerships and diplomacy, and highlights selected collaborative efforts that are aimed at improving cancer outcomes in the region.

Inhibition of tumor cell motility by the interferon-inducible GTPase MxA.

To identify pathways controlling prostate cancer metastasis we performed differential display analysis of the human prostate carcinoma cell line PC-3 and its highly metastatic derivative PC-3M. This revealed that a 78-kDa interferon-inducible GTPase, MxA, was expressed in PC-3 but not in PC-3M cells. The gene encoding MxA, MX1, is located in the region of chromosome 21 deleted as a consequence of fusion of TMPRSS2 and ERG, which has been associated with aggressive, invasive prostate cancer. Stable exogenous MxA expression inhibited in vitro motility and invasiveness of PC-3M cells. In vivo exogenous MxA expression decreased the number of hepatic metastases following intrasplenic injection. Exogenous MxA also reduced motility and invasiveness of highly metastatic LOX melanoma cells. A mutation in MxA that inactivated its GTPase reversed inhibition of motility and invasion in both tumor cell lines. Co-immunoprecipitation studies demonstrated that MxA associated with tubulin, but the GTPase-inactivating mutation blocked this association. Because MxA is a highly inducible gene, an MxA-targeted drug discovery screen was initiated by placing the MxA promoter upstream of a luciferase reporter. Examination of the NCI diversity set of small molecules revealed three hits that activated the promoter. In PC-3M cells, these drugs induced MxA protein and inhibited motility. These data demonstrate that MxA inhibits tumor cell motility and invasion, and that MxA expression can be induced by small molecules, potentially offering a new approach to the prevention and treatment of metastasis.