Intratumoral delivery of antigen with complement C3-bound liposomes reduces tumor growth in mice.

Antigen presenting cells (APCs) initiate the immune response against cancer by engulfing and presenting tumor antigens to T cells. Our lab has recently developed a liposomal nanoparticle that binds complement C3 proteins, allowing it to bind to the complement C3 receptors of APCs and directly deliver antigenic peptides. APCs were shown to internalize and process complement C3-bound liposomes containing ovalbumin (OVA), resulting in a significant increase in activated T cells that recognize OVA. Mice bearing A20-OVA lymphoma tumors were treated with OVA-loaded C3-liposomes, which led to reduced tumor growth in both treated and distal tumors in all mice. Peripheral blood from treated mice had a lower percentage of immunosuppressive myeloid derived suppressor cells (MDSCs), a higher percentage of B cells, and increased anti-OVA IgG1 levels compared to control mice. These results indicate that C3-liposome delivery of tumor antigen to APCs initiates a potent and systemic antitumor immune response.

Processes of code status transitions in hospitalized patients with advanced cancer.

BACKGROUND: Although hospitalized patients with advanced cancer have a low chance of surviving cardiopulmonary resuscitation (CPR), the processes by which they change their code status from full code to do not resuscitate (DNR) are unknown. METHODS: We conducted a mixed-methods study on a prospective cohort of hospitalized patients with advanced cancer. Two physicians used a consensus-driven medical record review to characterize processes that led to code status order transitions from full code to DNR. RESULTS: In total, 1047 hospitalizations were reviewed among 728 patients. Admitting clinicians did not address code status in 53% of hospitalizations, resulting in code status orders of "presumed full." In total, 275 patients (26.3%) transitioned from full code to DNR, and 48.7% (134 of 275 patients) of those had an order of "presumed full" at admission; however, upon further clarification, the patients expressed that they had wished to be DNR before the hospitalization. We identified 3 additional processes leading to order transition from full code to DNR acute clinical deterioration (15.3%), discontinuation of cancer-directed therapy (17.1%), and education about the potential harms/futility of CPR (15.3%). Compared with discontinuing therapy and education, transitions because of acute clinical deterioration were associated with less patient involvement (P = .002), a shorter time to death (P < .001), and a greater likelihood of inpatient death (P = .005). CONCLUSIONS: One-half of code status order changes among hospitalized patients with advanced cancer were because of full code orders in patients who had a preference for DNR before hospitalization. Transitions due of acute clinical deterioration were associated with less patient engagement and a higher likelihood of inpatient death. Cancer 2017;123:4895-902. © 2017 American Cancer Society.

Wound healing-like immune program facilitates postpartum mammary gland involution and tumor progression.

Women diagnosed with breast cancer within 5 years postpartum have poor survival rates. The process of postpartum mammary gland involution, whereby the lactating gland remodels to its prepregnant state, promotes breast cancer progression in xenograft models. Macrophage influx occurs during mammary gland involution, implicating immune modulation in the promotion of postpartum breast cancer. Herein, we characterize the postpartum murine mammary gland and find an orchestrated influx of immune cells similar to that which occurs during wound healing. Further, the normal involuting gland may be in an immunosuppressed state as discerned by the transient presence of Foxp3(+) regulatory T cells and IL-10(+) macrophages with T cell suppressive function. To determine the influence of the postpartum immune microenvironment on mammary tumor promotion, we developed an immune-competent model. In this model, mammary tumors in the involution group are sixfold larger than nulliparous group tumors, have decreased CD4(+) and CD8(+) T cell infiltrates and contain a greater number of macrophages with the ability to inhibit T cell activation. Targeting involution with a neutralizing antibody against the immunosuppressive cytokine IL-10 reduces tumor growth in involution group mice but not in nulliparous mice, implicating the involution microenvironment as the primary target of αIL-10 treatment. Relevance to women is implicated, as we find postlactational human breast tissue has transient high IL-10(+) and Foxp3(+) immune cell infiltrate. These data show an immune modulated microenvironment within the normal involuting mammary gland suggestive of immunosuppression, that when targeted reduces tumor promotion, revealing possible immune-based strategies for postpartum breast cancer.

Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution.

Mammary gland development is dependent on macrophages, as demonstrated by their requirement during the expansion phases of puberty and pregnancy. Equally dramatic tissue restructuring occurs following lactation, when the gland regresses to a state that histologically resembles pre-pregnancy through massive programmed epithelial cell death and stromal repopulation. Postpartum involution is characterized by wound healing-like events, including an influx of macrophages with M2 characteristics. Macrophage levels peak after the initial wave of epithelial cell death, suggesting that initiation and execution of cell death are macrophage independent. To address the role of macrophages during weaning-induced mammary gland involution, conditional systemic deletion of macrophages expressing colony stimulating factor 1 receptor (CSF1R) was initiated just prior to weaning in the Mafia mouse model. Depletion of CSF1R(+) macrophages resulted in delayed mammary involution as evidenced by loss of lysosomal-mediated and apoptotic epithelial cell death, lack of alveolar regression and absence of adipocyte repopulation 7 days post-weaning. Failure to execute involution occurred in the presence of milk stasis and STAT3 activation, indicating that neither is sufficient to initiate involution in the absence of CSF1R(+) macrophages. Injection of wild-type bone marrow-derived macrophages (BMDMs) or M2-differentiated macrophages into macrophage-depleted mammary glands was sufficient to rescue involution, including apoptosis, alveolar regression and adipocyte repopulation. BMDMs exposed to the postpartum mammary involution environment upregulated the M2 markers arginase 1 and mannose receptor. These data demonstrate the necessity of macrophages, and implicate M2-polarized macrophages, for epithelial cell death during normal postpartum mammary gland involution.

Complement C3 mediated targeting of liposomes to granulocytic myeloid derived suppressor cells.

In cancer patients, granulocytic myeloid derived suppressor cells (G-MDSCs) expand in number, infiltrating tumor and lymphatic tissues where they suppress an anti-tumor immune response. We report here the development of a liposomal drug delivery system that selectively targets G-MDSCs. The liposomes form a disulfide bond with activated complement C3 after intravenous injection and are taken up by G-MDSCs, which express the receptor for activated C3. In vitro experiments utilizing serum from a C3 knockout mouse demonstrate that G-MDSCs take up these liposomes in a C3-dependent manner. After systemic administration to tumor bearing mice, liposomes were incorporated by 22% of G-MDSCs in the blood and were also present in a percentage of G-MDSCs in the tumor (11%), spleen (22%), liver (35%) and lungs (26%). This liposomal system offers a versatile means of targeted drug delivery to G-MDSCs and could be an important tool for restoring anti-tumor immunity in cancer patients. FROM THE CLINICAL EDITOR: It has been shown that the presence of granulocytic myeloid derived suppressor cells (G-MDSCs) in cancer patients suppress the tumor immune response of T cells. Many drugs can be used to reverse this process. In this article, the authors describe the development of a liposomal drug delivery system for targeted drug delivery to G- MDSCs. This system may prove to be useful adjunct in immunotherapy in the fight against cancers.

Mammary gland involution as an immunotherapeutic target for postpartum breast cancer.

Postpartum mammary gland involution has been identified as tumor-promotional and is proposed to contribute to the increased rates of metastasis and poor survival observed in postpartum breast cancer patients. In rodent models, the involuting mammary gland microenvironment is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Postpartum involution shares many attributes with wound healing, including upregulation of genes involved in immune responsiveness and infiltration of tissue by immune cells. In rodent models, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) ameliorates the tumor-promotional effects of involution, consistent with the immune milieu of the involuting gland contributing to tumor promotion. Currently, immunotherapy is being investigated as a means of breast cancer treatment with the purpose of identifying ways to enhance anti-tumor immune responses. Here we review evidence for postpartum mammary gland involution being a uniquely defined 'hot-spot' of pro-tumorigenic immune cell infiltration, and propose that immunotherapy should be explored for prevention and treatment of breast cancers that arise in this environment.

Trophic disruption: a meta-analysis of how habitat fragmentation affects resource consumption in terrestrial arthropod systems.

Habitat fragmentation is a complex process that affects ecological systems in diverse ways, altering everything from population persistence to ecosystem function. Despite widespread recognition that habitat fragmentation can influence food web interactions, consensus on the factors underlying variation in the impacts of fragmentation across systems remains elusive. In this study, we conduct a systematic review and meta-analysis to quantify the effects of habitat fragmentation and spatial habitat structure on resource consumption in terrestrial arthropod food webs. Across 419 studies, we found a negative overall effect of fragmentation on resource consumption. Variation in effect size was extensive but predictable. Specifically, resource consumption was reduced on small, isolated habitat fragments, higher at patch edges, and neutral with respect to landscape-scale spatial variables. In general, resource consumption increased in fragmented settings for habitat generalist consumers but decreased for specialist consumers. Our study demonstrates widespread disruption of trophic interactions in fragmented habitats and describes variation among studies that is largely predictable based on the ecological traits of the interacting species. We highlight future prospects for understanding how changes in spatial habitat structure may influence trophic modules and food webs.

Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention.

The magnitude of the breast cancer problem implores researchers to aggressively investigate prevention strategies. However, several barriers currently reduce the feasibility of breast cancer prevention. These barriers include the inability to accurately predict future breast cancer diagnosis at the individual level, the need for improved understanding of when to implement interventions, uncertainty with respect to optimal duration of treatment, and negative side effects associated with currently approved chemoprevention therapies. None-the-less, the unique biology of the mammary gland, with its postnatal development and conditional terminal differentiation, may permit the resolution of many of these barriers. Specifically, lifecycle-specific windows of breast cancer risk have been identified that may be amenable to risk-reducing strategies. Here, we argue for prevention research focused on two of these lifecycle windows of risk: postpartum mammary gland involution and peri-menopause. We provide evidence that these windows are highly amenable to targeted, limited duration treatments. Such approaches could result in the prevention of postpartum and postmenopausal breast cancers, correspondingly.

GRASP [Genomic Resource Access for Stoichioproteomics]: comparative explorations of the atomic content of 12 Drosophila proteomes.

BACKGROUND: "Stoichioproteomics" relates the elemental composition of proteins and proteomes to variation in the physiological and ecological environment. To help harness and explore the wealth of hypotheses made possible under this framework, we introduce GRASP (http://www.graspdb.net), a public bioinformatic knowledgebase containing information on the frequencies of 20 amino acids and atomic composition of their side chains. GRASP integrates comparative protein composition data with annotation data from multiple public databases. Currently, GRASP includes information on proteins of 12 sequenced Drosophila (fruit fly) proteomes, which will be expanded to include increasingly diverse organisms over time. In this paper we illustrate the potential of GRASP for testing stoichioproteomic hypotheses by conducting an exploratory investigation into the composition of 12 Drosophila proteomes, testing the prediction that protein atomic content is associated with species ecology and with protein expression levels. RESULTS: Elements varied predictably along multivariate axes. Species were broadly similar, with the D. willistoni proteome a clear outlier. As expected, individual protein atomic content within proteomes was influenced by protein function and amino acid biochemistry. Evolution in elemental composition across the phylogeny followed less predictable patterns, but was associated with broad ecological variation in diet. Using expression data available for D. melanogaster, we found evidence consistent with selection for efficient usage of elements within the proteome: as expected, nitrogen content was reduced in highly expressed proteins in most tissues, most strongly in the gut, where nutrients are assimilated, and least strongly in the germline. CONCLUSIONS: The patterns identified here using GRASP provide a foundation on which to base future research into the evolution of atomic composition in Drosophila and other taxa.

Enhancing T Cell and Antibody Response in Mucin-1 Transgenic Mice through Co-Delivery of Tumor-Associated Mucin-1 Antigen and TLR Agonists in C3-Liposomes.

Mucin-1 (MUC1) is a highly relevant antigen for cancer vaccination due to its overexpression and hypo-glycosylation in a high percentage of carcinomas. To enhance the immune response to MUC1, our group has developed C3-liposomes that encapsulate the MUC1 antigen along with immunostimulatory compounds for direct delivery to antigen-presenting cells (APCs). C3-liposomes bind complement C3, which interacts with C3-receptors on APCs, resulting in liposomal uptake and the delivery of tumor antigens to APCs in a manner that mimics pathogenic uptake. In this study, MUC1 and Toll-like receptor (TLR) agonists were encapsulated in C3-liposomes to provoke an immune response in transgenic mice tolerant to MUC1. The immune response to the C3-bound MUC1 liposomal vaccine was assessed by ELISA, ELISpot, and flow cytometry. Co-administering TLR 7/8 agonists with MUC1 encapsulated in C3-liposomes resulted in a significant antibody response compared to non-encapsulated MUC1. This antibody response was significantly higher in females than in males. The co-encapsulation of three TLR agonists with MUC1 in C3-liposomes significantly increased antibody responses and eliminated sex-based differences. Furthermore, this immunization strategy resulted in a significantly increased T cell-response compared to other treatment groups. In conclusion, the co-delivery of MUC1 and TLR agonists via C3-liposomes greatly enhances the immune response to MUC1, highlighting its potential for antigen-specific cancer immunotherapy.

The positive effect of plant diversity on soil carbon depends on climate.

Little is currently known about how climate modulates the relationship between plant diversity and soil organic carbon and the mechanisms involved. Yet, this knowledge is of crucial importance in times of climate change and biodiversity loss. Here, we show that plant diversity is positively correlated with soil carbon content and soil carbon-to-nitrogen ratio across 84 grasslands on six continents that span wide climate gradients. The relationships between plant diversity and soil carbon as well as plant diversity and soil organic matter quality (carbon-to-nitrogen ratio) are particularly strong in warm and arid climates. While plant biomass is positively correlated with soil carbon, plant biomass is not significantly correlated with plant diversity. Our results indicate that plant diversity influences soil carbon storage not via the quantity of organic matter (plant biomass) inputs to soil, but through the quality of organic matter. The study implies that ecosystem management that restores plant diversity likely enhances soil carbon sequestration, particularly in warm and arid climates.

Critical patch sizes for food-web modules.

Because patch size and connectivity may strongly impact the assemblage of species that occur on a patch, the types of food-web interactions that occur among those species may also depend on spatial structure. Here, we identify whether food-web interactions among salt-marsh-inhabiting arthropods vary with patch size and connectivity, and how such changes in trophic structure might feed back to influence the spatial distribution of prey. In a multiyear survey, patch-restricted predators exhibited steeper occupancy-patch-size relationships than herbivores, and species' critical patch sizes were correlated with overall rarity. As a result, the presence of food-web modules depended strongly on patch size: large and well-connected patches supported complex food-web modules, but only the simplest modules involving the most abundant species were found on small patches. Habitat-generalist spiders dominated on small patches, and predation pressure from such species may contribute to the observed lower densities of mesopredators on small patches. Overall, patch size and connectivity influenced the types of modules present on a patch through differential loss of rare, patch-restricted predators, but predation by generalist predators may be a key mechanism influencing the spatial structure of certain prey species.

Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland.

The mammary gland is an excellent model system to study the interplay between stroma and epithelial cells because of the gland's unique postnatal development and its distinct functional states. This review focuses on the contribution of the extracellular matrix (ECM) to stromal-epithelial interactions in the mammary gland. We describe how ECM physical properties, protein composition, and proteolytic state impact mammary gland architecture as well as provide instructive cues that influence the function of mammary epithelial cells during pubertal gland development and throughout adulthood. Further, based on recent proteomic analyses of mammary ECM, we describe known mammary ECM proteins and their potential functions, as well as describe several ECM proteins not previously recognized in this organ. ECM proteins are discussed in the context of the morphologically-distinct stromal subcompartments: the basal lamina, the intra- and interlobular stroma, and the fibrous connective tissue. Future studies aimed at in-depth qualitative and quantitative characterization of mammary ECM within these various subcompartments is required to better elucidate the function of ECM in normal as well as in pathological breast tissue.

Recent advances in immune therapies for gastric cancer.

Gastric cancer (GC) is an aggressive malignancy that is the third leading cause of cancer mortality worldwide. Localized GC can be cured with surgery, but most patients present with more advanced non-operable disease. Until recently, treatment options for relapsed and refractory advanced GC have been limited to combination chemotherapy regimens, HER-2 directed therapy, and radiation, which lead to few durable responses. Over the past decade, there have been significant advances in our understanding of the molecular and immune pathogenesis of GC. The infectious agents Epstein-Barr virus and Helicobacter pylori perturb the gastric mucosa immune equilibrium, which creates a microenvironment that favors GC tumorigenesis and evasion of immune surveillance. Insights into immune mechanisms of GC have translated into novel therapeutics, including immune checkpoint inhibitors, which have become a treatment option for select patients with GC. Furthermore, chimeric antigen receptor T-cell therapies have emerged as a breakthrough treatment for many cancers, with recent studies showing this to be a potential therapy for GC. In this review, we summarize the current state of knowledge on immune mechanisms of GC and the status of emerging immunotherapies to treat this aggressive cancer, as well as outline current challenges and directions for future research.

Delivery of toll-like receptor agonists by complement C3-targeted liposomes activates immune cells and reduces tumour growth.

Activation of antigen presenting cells (APCs) is necessary for immune recognition and elimination of cancer. Our lab has developed a liposome nanoparticle that binds to complement C3 proteins present in serum. These C3-liposomes are specifically internalised by APCs and other myeloid cells, which express complement C3-binding receptors. Known immune stimulating compounds, toll-like receptor (TLR) agonists, were encapsulated within the C3-liposomes, including monophosphoryl lipid A (MPLA), R848, and CpG 1826, specific for TLR4, TLR7/8, and TLR9 respectively. When recognised by their respective TLRs within the myeloid cells, these compounds trigger signal cascades that ultimately lead to increased expression of inflammatory cytokines and activation markers (CD80, CD83, CD86 and CD40). RT-PCR analysis of murine bone marrow cells treated with C3-liposomes revealed a significant increase in gene expression of pro-inflammatory cytokines and factors (IL-1ß, IL-6, IL-12, TNF-α, IRF7, and IP-10). Furthermore, treatment of 4T1 tumour-bearing mice with C3-liposomes containing TLR agonists resulted in reduced tumour growth, compared to PBS treated mice. Collectively, these results demonstrate that C3-liposome delivery of TLR agonists activates APCs and induces tumour-specific adaptive immune responses, leading to reduced tumour growth in a breast cancer model.

Molecular Classification of Gastric Cancer among Alaska Native People.

Gastric cancer is an aggressive and heterogeneous malignancy that often varies in presentation and disease among racial and ethnic groups. The Alaska Native (AN) people have the highest incidence and mortality rates of gastric cancer in North America. This study examines molecular markers in solid tumor samples from eighty-five AN gastric adenocarcinoma patients using next-generation sequencing, immunohistochemistry, and in situ hybridization analysis. AN patients have a low mutation burden with fewer somatic gene mutations in their tumors compared to other populations, with the most common mutation being TP53. Epstein-Barr virus (EBV) was associated with 20% of AN gastric cancers, which is higher than the world average of 10%. The inflammation marker, cyclooxygenase-2 (COX-2), is highly expressed in patients with the lowest survival rates. Mismatch repair deficiency was present in 10% of AN patients and was associated with patients who were female, 50 years or older, gene mutations, and tumors in the distal stomach. Program death-ligand 1 (PD-L1) was expressed in 14% of AN patients who were more likely to have MMR deficiency, EBV-associated gastric cancers, and mutations in the PIK3CA gene, all of which have been linked to clinical response to PD-1 inhibitors. These studies suggest a portion of AN gastric cancer patients could be candidates for immunotherapy. Overall, this study highlights future avenues of investigation for clinical and translational studies, so that we can improve early detection and develop more effective treatments for AN patients.

Influence of Landscape Factors and Abiotic Conditions on Dispersal Behavior and Overwintering Site Selection by Halyomorpha halys (Hemiptera: Pentatomidae).

Since the initial detection of the invasive Halyomorpha halys (Stål) in the United States in the late 1990s, this insect has emerged as a severe agricultural and nuisance pest. Nuisance problems are due to adult dispersal to overwintering sites in the fall at which time they alight onto and eventually settle within human-made structures in addition to natural harborage. This study examined how three factors, elevation, light, and moisture affected overwintering site selection by H. halys in the mid-Atlantic. Observational counts performed along elevational transects revealed elevation was significant predictor of H. halys abundance during both years of the study in 2014 and 2015 with more adults observed at higher elevations. Choice tests examining effects of moisture and light on settling behavior demonstrated H. halys settled within overwintering shelter boxes in significantly greater numbers when shelters were dry compared with those having moist conditions, and in darkened shelters compared with those augmented with LED lights. Our findings indicate that H. halys use cues at both landscape and very localized levels when seeking and selecting overwintering sites.

Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson's Disease.

There is a principle in science, known as Occam's razor, that says the correct solution is usually the one with the simplest explanation. The microbiota-gut-brain axis, an interdependent series of communication loops between the enteric nervous system (ENS), the microbiota, the gut, and the brain, offers important insight into how changes in our gut affect distant organs like our brains. The inherent complexity of this axis with the crosstalk between the immune system, inflammatory states, and the thousands of bacteria, viral, and fungal species that together make up the microbiota make studying the interactions that govern this axis difficult and far from parsimonious. It is becoming increasingly clear that the microbiota is integral to this axis. Disruption of the healthy flora, a phenomenon collectively referred to as dysbiosis, has been implicated as a driver for several diseases such as irritable bowel syndrome, rheumatoid arthritis, obesity, diabetes, liver disease, and neurological disorders such as depression, anxiety, and Parkinson's disease (PD). Teasing apart these complex interactions as they pertain to PD is critical for our understanding of this debilitating disease, but more importantly, for the development of future treatments. So far, treatments have been unable to stop this neurodegenerative disease, succeeding only in briefly dampening symptoms and buying patients time before the inevitable loss of function ensues. Given that the 10 years prognosis for death or life-limiting disability with someone diagnosed with PD is upwards of 80%, there is a desperate need for curative treatments that go beyond symptom management. If PD does begin in the periphery with bidirectional communication between the microbiota and the immune system, as recent literature suggests, there is an exciting possibility that progression could be stopped before it reaches the brain. This systematic review assesses the current literature surrounding the role of the microbiota in the pathogenesis of alpha-synucleinopathies and explores the hypothesis that alpha-synuclein folding is modulated by the microbiota. Furthermore, we discuss how changes in the gut environment can lead to pathology and outline the implications that advances in understanding the interactions between host and microbiota will have on future research and the development of potential biomarkers.

Liposome Delivery of Natural STAT3 Inhibitors for the Treatment of Cancer.

In the tumor microenvironment, cytokines, growth factors, and oncogenes mediate constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in both cancer cells and infiltrating immune cells. STAT3 activation in cancer cells drives tumorigenic changes that allow for increased survival, proliferation, and resistance to apoptosis. The modulation of immune cells is more complicated and conflicting. STAT3 signaling drives the myeloid cell phenotype towards an immune suppressive state, which mediates T cell inhibition. On the other hand, STAT3 signaling in T cells leads to proliferation and T cell activity required for an anti-tumor response. Targeted delivery of STAT3 inhibitors to cancer cells and myeloid cells could therefore improve therapeutic outcomes. Many compounds that inhibit the STAT3 pathways for cancer treatment include peptide drugs, small molecule inhibitors, and natural compounds. However, natural compounds that inhibit STAT3 are often hydrophobic, which reduces their bioavailability and leads to unfavorable pharmacokinetics. This review focuses specifically on liposome-encapsulated natural STAT3 inhibitors and their ability to target cancer cells and myeloid cells to reduce tumor growth and decrease STAT3-mediated immune suppression. Many of these liposome formulations have led to profound tumor reduction and examples of combination formulations have been shown to eliminate tumors through immune modulation.

Gastric cancer in Alaska Native people: A cancer health disparity.

AIM: To evaluate recent trends in gastric cancer incidence, response to treatment, and overall survival among Alaska Native (AN) people. METHODS: A retrospective analysis of the Alaska Native Medical Center patient database was performed. Patient history, clinical, pathological, response to treatment and patient outcomes were collected from one-hundred and thirty-two AN gastric cancer patients. The Surveillance, Epidemiology and End Result database 18 was used to collect comparison United States non-Hispanic White (NHW) and AN gastric cancer patient data between 2006-2014. RESULTS: AN gastric cancer patients have a higher incidence rate, a poorer overall survival, and are diagnosed at a significantly younger age compared to NHW patients. AN patients differ from NHW patients in greater prevalence of non-cardia, diffuse subtype, and signet ring cell carcinomas. AN females were more likely to be diagnosed with later stage cancer, stage IV, compared to AN males. Diminished overall survival was observed among AN patients with increasing stage, O+ blood type, < 15 lymph nodes examined at resection, and no treatment. This study is the first report detailing the clinicopathologic features of gastric cancer in AN people with outcome data. CONCLUSION: Our findings confirm the importance of early detection, treatment, and surgical resection for optimizing AN patient outcomes. Further research on early detection markers are warranted.