Nearby Cells Research Articles

B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role.

(1) Aim: Medulloblastoma is the most common aggressive pediatric cancer of the central nervous system. Improved therapies are necessary to improve life outcomes for medulloblastoma patients. Exosomes are a subset of extracellular vesicles that are excreted outside of the cell, and can transport nucleic acids and proteins from donor cells to nearby recipient cells of the same or dissimilar tissues. Few publications exist exploring the role that exosomes play in medulloblastoma pathogenesis. In this study, we found B7-H3, an immunosuppressive immune checkpoint, present in D283 cell-derived exosomes. (2) Methods: Utilizing mass spectrometry and immunoblotting, the presence of B7-H3 in D283 control and B7-H3 overexpressing exosomes was confirmed. Exosomes were isolated by Systems Biosciences from cultured cells as well as with an isolation kit that included ultracentrifugation steps. Overlay experiments were performed to determine mechanistic impact of exosomes on recipient cells by incubating isolated exosomes in serum-free media with target cells. Impact of D283 exosome incubation on endothelial and UW228 medulloblastoma cells was assessed by immunoblotting. Immunocytochemistry was employed to visualize exosome fusion with recipient cells. (3) Results: Overexpressing B7-H3 in D283 cells increases exosomal production and size distribution. Mass spectrometry revealed a host of novel, pathogenic molecules associated with B7-H3 in these exosomes including STAT3, CCL5, MMP9, and PI3K pathway molecules. Additionally, endothelial and UW228 cells incubated with D283-derived B7-H3-overexpressing exosomes induced B7-H3 expression while pSTAT1 levels decreased in UW228 cells. (4) Conclusions: In total, our results reveal a novel role in exosome production and packaging for B7-H3 that may contribute to medulloblastoma progression.

HIPK2 Is Required for Midbody Remnant Removal Through Autophagy-Mediated Degradation.

At the end of abscission, the residual midbody forms the so-called midbody remnant (MBR), a platform affecting cell fate with emerging key role in differentiation, development, and tumorigenicity. Depending on cell type and pathophysiological context, MBRs undergo different outcomes: they can be retained, released, internalized by nearby cells, or removed through autophagy-mediated degradation. Although mechanisms underlying MBR formation, positioning, and processing have been recently identified, their regulation is still largely unknown. Here, we report that the multifunctional kinase HIPK2 regulates MBR processing contributing to MBR removal. In the process of studying the role of HIPK2 in abscission, we observed that, in addition to cytokinesis failure, HIPK2 depletion leads to significant accumulation of MBRs. In particular, we detected comparable accumulation of MBRs after HIPK2 depletion or treatment with the autophagic inhibitor chloroquine. In contrast, single depletion of the two independent HIPK2 abscission targets, extrachromosomal histone H2B and severing enzyme Spastin, only marginally increased MBR retention, suggesting that MBR accumulation is not just linked to cytokinesis failure. We found that HIPK2 depletion leads to (i) increased levels of CEP55, a key effector of both midbody formation and MBR degradation; (ii) decreased levels of the selective autophagy receptors NBR1 and p62/SQSTM1; and (iii) impaired autophagic flux. These data suggest that HIPK2 contributes to MBR processing by regulating its autophagy-mediated degradation.

Calcium Dynamics in Astrocytes During Cell Injury.

The changes in intracellular calcium concentration ([Ca2+]) following laser-induced cell injury in nearby cells were studied in primary mouse astrocytes selectively expressing the Ca2+ sensitive GFAP-Cre Salsa6f fluorescent tandem protein, in an Ast1 astrocyte cell line, and in primary mouse astrocytes loaded with Fluo4. Astrocytes in these three systems exhibit distinct changes in [Ca2+] following induced death of nearby cells. Changes in [Ca2+] appear to result from release of Ca2+ from intracellular organelles, as opposed to influx from the external medium. Salsa6f expressing astrocytes displayed dynamic Ca2+ changes throughout the phagocytic response, including lamellae protrusion, cytosolic signaling during vesicle formation, vesicle maturation, and vesicle tract formation. Our results demonstrate local changes in [Ca2+] are involved in the process of phagocytosis in astrocytes responding to cell corpses and/or debris.

Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems.

Cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) are a family of defence systems against bacteriophages (hereafter phages) that share ancestry with the cGAS-STING innate immune pathway in animals. CBASS systems are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic oligonucleotides and promotes cell death. Cell death occurs before phage replication is completed, therefore preventing the spread of phages to nearby cells. Here, we analysed 38,000 bacterial and archaeal genomes and identified more than 5,000 CBASS systems, which have diverse architectures with multiple signalling molecules, effectors and ancillary genes. We propose a classification system for CBASS that groups systems according to their operon organization, signalling molecules and effector function. Four major CBASS types were identified, sharing at least six effector subtypes that promote cell death by membrane impairment, DNA degradation or other means. We observed evidence of extensive gain and loss of CBASS systems, as well as shuffling of effector genes between systems. We expect that our classification and nomenclature scheme will guide future research in the developing CBASS field.

Abstract 322: A unique ex vivo tumor model: 3D co-cultured system with cancer cells and stromal tissue for drug evaluation

Abstract Background;Recently, three-dimensional culture model has been reported as better tumor model than 2D culture. The importance of interaction between cancer and stromal cells has been widely recognized in tumor progression and resistance against treatment. So that ex vivo model which recaptures the tumor microenvironment is required to perform drug evaluation mimicking the patient tumor tissue. Methods; Layered 3D stromal tissues with microvascular network were produced by culturing normal fibroblasts and endothelial cells coated with the extra-cellular matrix (ECM) and natural polysaccharide, namely collagen and heparin. The layered 3D stromal tissues and co-cultured tumor were morphologically evaluated by HE staining, immunohistochemistry and immunofluorescence (IF). Drug sensitivity assay were conducted using popular colorectal cancer cell lines, and patient-derived cell lines (PDCs) established in JFCR under approved IRB. Remaining cancer cells post drug treatment were quantified by IF and imaging analysis. Furthermore, in vivo drug sensitivity was also evaluated. Results: The CD31 positive luminal structures which shows vascular endothelial tube formation were observed intra multi-layered tissues. The dense microvascular network tended to be formed nearby cancer cells. In comparison with 2D culture model, decreased drug sensitivities were represented in the layered 3D co-cultured model. The evaluated drug sensitivities in 3D model may reflect the response of cancer cells in in vivo. Conclusion; We developed the layered 3D stromal tissue culture system including blood micro-vessels. Our unique 3D ex vivo model appear to be a valuable tool for drug evaluation, and thus further studies are underway to confirm the usefulness of our model. Testing approved and/or developing compounds with PDCs in the model would potentially enable better prediction their efficacy. Citation Format: Yuki Takahashi, Kei Tsukamoto, Yuki Shimizu, Ryohei Katayama, Eiji Shinozaki, Satoshi Nagayama, Michiya Matsusaki, Shiro Kitano, Kensei Yamaguchi, Naoya Fujita. A unique ex vivo tumor model: 3D co-cultured system with cancer cells and stromal tissue for drug evaluation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 322.

Abstract 3356: Annexin-A1 as a potential therapeutic target for solid tumors

Abstract Significant challenges persist in developing novel, less toxic, more effective therapies for clinically challenging cancers with relatively low response rates to treatment. Moreover, additional treatment options for refractory and drug resistant cancers are urgently required. Annexin-A1 (ANXA1), a member of a protein superfamily that binds acidic phospholipids in a calcium-dependent manner, is normally localized in cell cytoplasm or plasma membrane. However, ANXA1 can be secreted in response to cell activation and can then modulate the behaviors of nearby cells by binding to the formyl peptide receptor 2 (FPR2). Current literature strongly suggests that ANXA1 can act as a tumor suppressor or an oncogene dependent on cancer indication/subtype, playing a significant role in many upstream signalling pathways that direct cancer proliferation, angiogenesis, drug resistance, invasion and metastasis. Our hypothesis was that annexin-A1 would be a novel target for anti-cancer therapy. We have developed a humanized antibody targeting ANXA1 (MDX-124) and here we present data showing its cytotoxic effect on a panel of cancer cell lines and in a mouse model of triple negative breast cancer. Results: Incubation of a selected panel of breast, colorectal, pancreatic and ovarian cancer cell lines with MDX-124 (0-10 µM) for 72h resulted in a statistically significant reduction in cell survival compared to incubation with an IgG isotype control which binds in a non-specific manner or a commercially available anti-ANXA1 polyclonal antibody. MDX-124 has been assessed for binding affinity to ANXA1 by Biacore and found to have a low nM KD, whilst the potency of MDX-124 was evaluated to be in the low nM range using MCF-7 cells in the CellTiter-Glo® luminescent cell viability assay. ANXA1 localization was also assessed across the panel of cell lines using imaging flow cytometry to quantitate ANXA1 in different cellular compartments. We found the cytotoxic effect of MDX-124 correlated with strong ANXA1 membrane staining. Further in-vivo studies utilized MDX-124 (1 mg/kg) in the syngeneic orthotopic 4T1-luc triple negative breast cancer model. Following dosing once a week we identified a statistically significant reduction in the rate of increase in tumor volume compared to the vehicle control which was not associated with any significant change in body weight. Therefore, our results demonstrate that cancer cell growth is suppressed by inhibition of ANXA1 and indicate that MDX-124 is a promising targeted antibody therapeutic against cancers overexpressing ANXA1. Further studies are under way to determine the mechanism of cell kill by MDX-124. Citation Format: Fiona C. Dempsey, Henry C. Hays, Scott J. Crichton, Hussein Al-Ali, Christopher N. Parris. Annexin-A1 as a potential therapeutic target for solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3356.

Abstract 4519: Photochemically-primed immune cell enrichment and anti-tumor responses to pancreatic cancer

Abstract Pancreatic adenocarcinoma (PDAC) is among the deadliest forms of cancer. Currently, it is the third leading cause of cancer deaths in the United States. At diagnosis, the majority of patients present with advanced primary or metastatic disease that is unresectable. PDAC pathophysiology is challenging for current therapies as immunosuppressive desmoplastic stroma limits responsiveness to treatments including immunotherapy. The latter condition is making a vast proportion of PDAC tumors being immunologically cold as defined by the lack of effective immune infiltration to the tumor. Thus, there is an unmet need for improved treatment strategies. Photodynamic therapy (PDT) is an approved modality that utilizes light, a photo-responsive photosensitizer (PS), and oxygen to generate reactive oxygen species that will kill nearby cells or prime neighboring cells to be more responsive to traditional therapies, and thereby produce a synergistic outcome. We aimed to investigate PDT-induced immunogenicity in PDAC tumors. In this study, we applied PDT in an immunocompetent mouse (C57BL/6 mice), PDAC tumor model and assessed tumour-infiltrating lymphocyte (TIL) infiltration at different time points. Visudyne® used as the PS. Multicolor flow cytometric analysis showed gradual increase of T and B cell infiltration at 1h time point to 5 days after PDT. T cell subset analysis showed a higher infiltration of CD8+ T cells with time. Localization of immune cells using immunofluorescence assays further confirmed latter findings. We observed a presence of proliferating T cells in the T cell zone of Spleen B cell follicles 1h after treating with PDT suggesting an early T cell activation. Activated dendritic cells were localized in the spleens treated with PDT compared to the untreated control. We further evaluated the anti-tumour immune reactivity of CD8+ T cells treated with PDT in an in vitro 3D system consisting of human PDAC cell line, MiaPaCa2, pancreatic fibroblast and human peripheral blood mononuclear cell co-culture. Tumor reactivity by CD8+ T cells was evaluated at baseline, 3 days, 7 days and 2 weeks in co-culture after PDT by staining for the surface expression of degranulation marker CD107a. There was a continuous CD107a upregulation in CD8+ T cells from day 3 to 2 week in co-culture treated with PDT compared to untreated controls demonstrating enhanced PDT priming of T cells, in vitro. In addition, there was an effective tumor cell killing in PDT treated immune-tumour co-cultures. Our data shows a possibility of triggering an immediate and effective immune-response to PDT in PDAC tumors enhancing the immunogenicity of this tumor type. Citation Format: Pushpamali De Silva, Mohammad Ahsan Saad, Assiris P. Camargo, Joseph Swain, Akilan Palanasami, Tayyaba Hasan. Photochemically-primed immune cell enrichment and anti-tumor responses to pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4519.

Functions and applications of metallic and metallic oxide nanoparticles in orthopedic implants and scaffolds.

Bone defects and diseases are devastating, and can lead to severe functional deficits or even permanent disability. Nevertheless, orthopedic implants and scaffolds can facilitate the growth of incipient bone and help us to treat bone defects and diseases. Currently, a wide range of biomaterials with distinct biocompatibility, biodegradability, porosity, and mechanical strength is used in bone-related research. However, most orthopedic implants and scaffolds have certain limitations and diverse complications, such as limited corrosion resistance, low cell proliferation, and bacterial adhesion. With recent advancements in materials science and nanotechnology, metallic and metallic oxide nanoparticles have become the subject of significant interest as they offer an ample variety of options to resolve the existing problems in the orthopedic industry. More importantly, these nanoparticles possess unique physicochemical and mechanical properties not found in conventional materials, and can be incorporated into orthopedic implants and scaffolds to enhance their antimicrobial ability, bioactive molecular delivery, mechanical strength, osteointegration, and cell labeling and imaging. However, many metallic and metallic oxide nanoparticles can also be toxic to nearby cells and tissues. This review article will discuss the applications and functions of metallic and metallic oxide nanoparticles in orthopedic implants and bone tissue engineering.

Classifying the Linkage between Adipose Tissue Inflammation and Tumor Growth through Cancer-Associated Adipocytes.

Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

A Simple and Efficient Method for Visualizing Individual Cells in vivo by Cre-Mediated Single-Cell Labeling by Electroporation (CREMSCLE).

Efficient methods for visualizing cell morphology in the intact animal are of great benefit to the study of structural development in the nervous system. Quantitative analysis of the complex arborization patterns of brain cells informs cell-type classification, dissection of neuronal circuit wiring, and the elucidation of growth and plasticity mechanisms. Time-lapse single-cell morphological analysis requires labeling and imaging of single cells in situ without contamination from the ramified processes of other nearby cells. Here, using the Xenopus laevis optic tectum as a model system, we describe CRE-Mediated Single-Cell Labeling by Electroporation (CREMSCLE), a technique we developed based on bulk co-electroporation of Cre-dependent inducible expression vectors, together with very low concentrations of plasmid encoding Cre recombinase. This method offers efficient, sparse labeling in any brain area where bulk electroporation is possible. Unlike juxtacellular single-cell electroporation methods, CREMSCLE relies exclusively on the bulk electroporation technique, circumventing the need to precisely position a micropipette next to the target cell. Compared with viral transduction methods, it is fast and safe, generating high levels of expression within 24 h of introducing non-infectious plasmid DNA. In addition to increased efficiency of single-cell labeling, we confirm that CREMSCLE also allows for efficient co-expression of multiple gene products in the same cell. Furthermore, we demonstrate that this method is particularly well-suited for labeling immature neurons to follow their maturation over time. This approach therefore lends itself well to time-lapse morphological studies, particularly in the context of early neuronal development and under conditions that prevent more difficult visualized juxtacellular electroporation.

Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression.

Targeting the cross-talk between tumor-initiating cells (TICs) and the niche microenvironment is an attractive avenue for cancer therapy. We show here, using a mouse model of squamous cell carcinoma, that TICs play a crucial role in creating a niche microenvironment that is required for tumor progression and drug resistance. Antioxidant activity in TICs, mediated by the transcription factor NRF2, facilitates the release of a nuclear cytokine, interleukin-33 (IL-33). This cytokine promotes differentiation of macrophages that express the high-affinity immunoglobulin E receptor FcεRIα and are in close proximity to TICs. In turn, these IL-33-responding FcεRIα+ macrophages send paracrine transforming growth factor β (TGF-β) signals to TICs, inducing invasive and drug-resistant properties and further upregulating IL-33 expression. This TIC-driven, IL-33-TGF-β feedforward loop could potentially be exploited for cancer treatment.

Deconstructing a perilous loop

Cancer Cancer cells that give rise to solid tumors reside in a specialized microenvironment containing growth factors that support tumor growth and progression. The mechanisms by which tumor cells within this so-called “niche” attract and sustain these growth factors are poorly understood. Studying a mouse model of squamous cell carcinoma, Taniguchi et al. identified a signaling loop initiated by certain tumor cells within the niche that become more invasive on exposure to transforming growth factor β (TGF-β). They show that the tumor cells release the cytokine interleukin-33, which induces the differentiation of nearby myeloid cells into macrophages. These macrophages in turn release TGF-β, which feeds back to the tumor cells, promoting their malignant progression. Science this issue p. [eaay1813][1] [1]: /lookup/doi/10.1126/science.aay1813

Advances in Molecular Mechanisms for Traditional Chinese Medicine Actions in Regulating Tumor Immune Responses.

Traditional Chinese medicine (TCM) has been developed for thousands of years with its various biological activities. The interest in TCM in tumor prevention and treatment is rising with its synergistic effect on tumor cells and tumor immunosuppressive microenvironment (TIM). Characteristic of TCM fits well within the whole system and multi-target cancer treatment. Herein we discuss the underlying mechanisms of TCM actions in TIM via regulating immunosuppressive cells, including restoring the antigen presentation function of dendritic cells, enhancing NK cells-mediated killing activity, restraining the functions of myeloid cell-derived suppressor cells, and inhibiting cancer-associated fibroblasts. TCM also regulates tumor progression through enhancing immune response, preventing immune escape and inducing cell death of tumor cells, which triggers immune response in nearby cells. In addition, we discuss TCM in clinical applications and the advantages and disadvantages of TCM in cancer prevention and treatment, as well as current therapeutic challenges and strategies. It might be helpful for understanding the therapeutic potential of TCM for cancer in clinic.

Abortive Infection: Bacterial Suicide as an Antiviral Immune Strategy.

Facing frequent phage challenges, bacteria have evolved numerous mechanisms to resist phage infection. A commonly used phage resistance strategy is abortive infection (Abi), in which the infected cell commits suicide before the phage can complete its replication cycle. Abi prevents the phage epidemic from spreading to nearby cells, thus protecting the bacterial colony. The Abi strategy is manifested by a plethora of mechanistically diverse defense systems that are abundant in bacterial genomes. In turn, phages have developed equally diverse mechanisms to overcome bacterial Abi. This review summarizes the current knowledge on bacterial defense via cell suicide. It describes the principles of Abi, details how these principles are implemented in a variety of natural defense systems, and discusses phage counter-defense mechanisms.

Micropatterned Growth Surface Topography Affects Extracellular Vesicle Production

Extracellular vesicles (EVs) are micro and nanoscale packages that circulate in all bodily fluids and play an important role in intercellular communication by shuttling biomolecules to nearby and distant cells. However, producing sufficient amounts of EVs for many types of in vitro studies using standard culture methods can be challenging, and despite the success of some bioreactors in increasing EV-production, it is still largely unknown how individual culture conditions can alter the production and content of EVs. In this study, we demonstrate a simple and inexpensive micropatterning technique that can be used to produce polystyrene microtracks over a 100 mm diameter growth surface area. We then demonstrate that these microtracks can play a significant role in increasing EV production using a triple-negative breast cancer cell line (MDA-MB-231) and that these changes in EV production correlate with increases in cellular aspect ratio, alignment of the cells' long axes to the microtrack direction, and single-cell migration rates. These findings have implications in both biomanufacturing of EVs and potentially in enhancing the biomimicry of EVs produced in vitro.

Rafflesia patma Blume flower organs: histology of the epidermis and vascular structures, and a search for stomata.

A histological study of Rafflesia patma revealed the simplicity of a flower's vascular tissue and epidermal features of flower organs, including their structures and pigmentation. Rafflesia is an endophytic holoparasitic plant that infects Tetrastigma. In a previous study, we characterized the shape of the strands of an endophyte (Rafflesia patma Blume) and hypothesized their distribution. In this study, we deepened our analysis by assessing parts of flower tissue sampled during anthesis, performed surface casting of the abaxial and adaxial sides of the perigone lobe to profile their surface features, and histologically characterized the perigone lobe, perigone tube, and central column base, including the anther and cupula region. The objective of these observations was to compare tissues from different organs and the distribution of cells staining positive for tannin, suberin, and lignin. Observable features in this study were vascular and epidermal tissue. We also observed reduced vascular tissue with xylem and vascular parenchyma in multiple organs. The adaxial epidermis found in the perigone lobes and tube had papillate cells, and their function might be to assist with the emission of odor through chemical evaporation. The abaxial epidermis, also found in perigone lobes and tube, had flattened cells. These, combined with the nearby flattened parenchyma cells, especially in the outermost, early perigone lobe, might provide a tougher (stiffer) outer protective barrier for the flower. The accumulation of tannin in perigone lobes might offer protection to the flower from herbivores prior to anthesis. Although a previous observation indicated the possibility of stomata on the surface of Rafflesia flowers, no stomata were found in this study.

Efficient blockade of locally reciprocated tumor-macrophage signaling using a TAM-avid nanotherapy.

Interpreting how multicellular interactions in the tumor affect resistance pathways to BRAF and MEK1/2 MAPK inhibitors (MAPKi) remains a challenge. To investigate this, we profiled global ligand-receptor interactions among tumor and stromal/immune cells from biopsies of MAPK-driven disease. MAPKi increased tumor-associated macrophages (TAMs) in some patients, which correlated with poor clinical response, and MAPKi coamplified bidirectional tumor-TAM signaling via receptor tyrosine kinases (RTKs) including AXL, MERTK, and their ligand GAS6. In xenograft tumors, intravital microscopy simultaneously monitored in situ single-cell activities of multiple kinases downstream of RTKs, revealing MAPKi increased TAMs and enhanced bypass signaling in TAM-proximal tumor cells. As a proof-of-principle strategy to block this signaling, we developed a multi-RTK kinase inhibitor nanoformulation that accumulated in TAMs and delayed disease progression. Thus, bypass signaling can reciprocally amplify across nearby cell types, offering new opportunities for therapeutic design.

SUN-LB26 Radioligand Theranostics of Endocrine-Related Cancers; A New, Revolutionary Approach

The successful clinical development of octreotide targeting somatostatin receptors (SSRs) revolutionized treatment of Neuro Endocrine Tumors (NETs)and pituitary adenomas. Recently, clinical applications of peptide bioconjugates including octreotide have taken a giant leap forward into a new diagnostic and therapeutic arena of additional endocrine-related cancers including prostate, breast, and small cell lung cancers. Molecularly targeted radionuclide therapy (RT) opens new horizons for otherwise resistant or widely dispersed malignancies and has far-reaching implications as a personalized therapeutic approach. Cancer-type specific, radiolabeled diagnostic imaging agents have been developed to select patients who then receive precise radioligand therapy targeting the identified cancer cells. This RT using alpha or beta radiation is cytotoxic to targeted cancer cells, while nearby healthy cells are unharmed—minimizing side effects and improving patient quality of life. Thus, theranostics represent a groundbreaking approach to bring radionuclide endocrine cancer therapy to patients via a multidisciplinary team consisting of endocrinologists, surgeons, oncologists and nuclear medicine physicians. In recognition of this exploding new field, the US FDA approved 68Ga-DOTATOC and -DOTATATE for use in PET/CT and 177Lu-DOTATATE for the treatment of SSR-positive NETs. Clinical trials with new theranostic compounds are ongoing for prostate cancer (PSMA), breast cancer (bombesin receptor), and small cell lung cancer (cytokine receptor CXCR4). Exciting future developments will undoubtedly involve development of radionuclide agents targeting additional cell surface receptors, enzymatic pathways, and clonal variations as well as combinations of alpha- and beta-emitters. Health care facilities worldwideare in the process of adding RT to their armamentarium for cancer patients; this requires a multidisciplinary team approach to optimize access to and delivery of care. To advance the science and enable translation of theranostics worldwide, the Gordon Research Conferences (GRC) organization [www.grc.org] has selected the authors to organize a 5-day inaugural meeting on Radionuclide Theranostics for the Management of Cancer in June 2020 [https://www.grc.org/radionuclide-theranostics-for-the-management-of-cancer-conference/2020/]that brings together cancer biologists, radiation physicists, receptor pharmacologists, nuclear medicine physicians, and industry representatives to 1) Identify new molecular targets and targeting vectors for specific malignancies; 2) Explore development of novel radionuclides and molecularly targeted radiopharmaceuticals; and 3) Optimize therapeutic benefits based on an understanding of radionuclide risks to normal tissues. This presentation will review the key topics discussed during this GRC meeting2496 characters (without spaces): limit 2500.

A framework for setting up a country-wide network of regional surface PM2.5 sampling sites utilising a satellite-derived proxy – The COALESCE project, India

Abstract Air quality management and assessment of aerosol climate effects over a large area require the strategic placement of regionally representative monitoring sites (RRMS) to capture the required information. Ground-based, fine particulate matter (PM2.5) concentrations measured for a long duration at high spatial resolution i.e. at several potential locations in a region help identify an optimal regionally representative site for the monitoring network. However, in the absence of long-term PM2.5 concentrations with high spatial resolution, identification of RRMS is a challenge. To identify for such situations, a novel methodology utilising satellite-derived PM2.5 is presented in this study. High spatial resolution (1 km × 1 km) daily aerosol optical depth (AOD) over several years (2004–2011) is used to derive surface PM2.5 using appropriate conversion factors. PM2.5 concentrations thus derived for a potential site and its nearby cells in the region are subjected to statistical analysis, to quantify linear/non-linear relationships between the respective PM2.5 time-series. Metrics such as coefficient of divergence (CoD), Pearson correlation coefficient (PCC) and Mutual information (MI) are calculated to assess the regional representativeness of a site. These criteria combined with physical criteria such as proximity of the site to local sources, local meteorology analysis and clustered air parcel back-trajectory analysis, are used in a weight-of-evidence approach to establish site adequacy. The selection and validation of eleven sites for the COALESCE project, is used as an illustrative example, to demonstrate the effectiveness of the site-selection methodology developed in this study.

Nanonetworks and Molecular Communications for Biomedical Applications

For millions of years, cells have evolved to perform incredible functions in all living organisms despite their nanoscale size. Consider white blood cells. They are fighting a never-ending war against bacteria, viruses, and other threats that enter your body. They produce vital antibodies to destroy pathogens in ways that almost seem as if the cells are independently communicating. And yes, this is true: cells do communicate, typically through the release of chemical compounds that trigger responses in nearby cells. To give a specific example related to white blood cells, basophils (a type of white blood cell) release histamines, which prompt blood vessels to dilate near the affected area of the body. This increases blood flow to the region, allowing for more white blood cells to reach the area and at tack suspected pathogens nearby.