Tissue Sites Research Articles

Genomic biomarkers of survival in patients with metastatic hormone-sensitive prostate cancer undergoing intensified androgen deprivation therapy.

Androgen deprivation therapy intensification (ADTi) with androgen receptor pathway inhibitors (ARPI), docetaxel or both has been shown to improvesurvival outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Currently, baseline tumor genomic markers have no role in clinical decision-making in patients with mHSPC. In this IRB-approved retrospective study, patients diagnosed with mHSPC who underwent comprehensive genomic profiling from primary tissue or metastatic sites and treated with ADTi were included. Genomic alterations with an incidence ≥5% were included in the analysis. A total of 276 patients were eligible and included in the study. In the multivariable analysis, TP53 (HR 1.71, 95% CI 1.17-2.49, p = 0.006), RB1 (HR 2.32, 95% CI 1.28-4.18, p = 0.006), PTEN (HR 1.74, 95% CI 1.12-2.7, p = 0.014), and BRCA2 (HR 2.64, 95% CI 1.42-4.92, p = 0.003) were associated with significantly shorter PFS, while TP53 (HR 1.63, 95% CI 1.00-2.64, p = 0.049), RB1 (HR 4.5, 95% CI 2.32-8.70, p < 0.001), and PTEN (HR 2.4, 95% CI 1.38-4.2, p = 0.003) were associated with significantly worse OS. This is one of the largest studies to show the association of baseline tumor genomic markers with survival in patients with mHSPC treated with ADTi. Upon external validation, these results may aid in developing a clinical-genomic risk stratification model, patient counseling, and prognostication.

Expression Pattern Analyzation and Regulation Genes Identification on the Purple Phenotype in the Different Tissues of the Purple Pak-choi and Zicaitai

Among the Brassica species in China, including Chinese cabbage, pak-choi, caixin, zicaitai, and wucai, Brassica rapa plays an important role in vegetable production. Purple resources from the species itself are scarce. It is worth noting that the tissue positions expressing a purple phenotype vary greatly between purple pak-choi and zicaitai. In this study, the genetic patterns of the purple phenotype were analyzed in purple pak-choi and zicaitai, and the F1 showed purple leaves and green stems, which indicated that purple traits in the leaves and stem were inherited independently. In conjunction with field identification, RNA-seq was used to sequence the transcriptomes of the purple expression sites of purple pak-choi, zicaitai, and their F1. The high expression of the regulatory genes Dark_pur and BrTT8 affected the purple color of pak-choi and caused the high expression of structural genes of the anthocyanin metabolism pathway and the accumulation of anthocyanins in leaves. The regulatory genes BrPAP2 and BrTT8 affected the purple color of zicaitai stems, were significantly upregulated, and caused high expression of related structural genes, leading to the accumulation of anthocyanins in the stem epidermis. This suggested that BrPAP2 and Dark_pur were both R2R3-MYB transcription factors, which were tissue-specific for the regulation of purple color traits in B. rapa. They also had a gene epistatic effect, which influenced the expression of purple traits in the F1. The gene MYBL2 was highly expressed in all purple tissue sites. The present study on the regulatory genes of the purple phenotype of zicaitai and purple pak-choi provides a theoretical basis for revealing the influence of purple traits on B. rapa leaves and stems, and it may lay the foundation for the selection and breeding of purple vegetables of B. rapa.

The human and non-human primate developmental GTEx projects.

Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows. In parallel, little is known about the conservation of developmental programmes across non-human primate (NHP) species, with implications for human evolution. Here we introduce the developmental Genotype-Tissue Expression (dGTEx) projects, which span humans and NHPs and aim to integrate gene expression, regulation and genetics data across development and species. The dGTEx cohort will consist of 74 tissue sites across 120 human donors from birth to adulthood, and developmentally matched NHP age groups, with additional prenatal and adult animals, with 126 rhesus macaques (Macaca mulatta) and 72 common marmosets (Callithrix jacchus). The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development. Through community engagement and donor diversity, the human dGTEx study seeks to address disparities in genomic research. Thus, dGTEx will provide a reference human and NHP dataset and tissue bank, enabling research into developmental changes in expression and gene regulation, childhood disorders and the effect of genetic variation on development.

Lower Extremity Soft Tissue Defect Reconstruction Using the SCIP Free Flap: A Comprehensive Review

The reconstruction of lower extremity soft tissue defects requires a flap capable of covering vital foot structures while withstanding the stresses of walking and shoe pressure. The Superficial Circumflex Iliac Artery Perforator (SCIP) flap provides finely detailed tissue and minimal donor site sequelae. Its surgical technique is safe, accessible, and benefits from preoperative echo-Doppler mapping for enhanced precision. The SCIP flap's numerous advantages make it an essential component in the plastic surgeon's decision-making algorithm for lower extremity soft tissue reconstruction, offering a renewed perspective on inguinal donor site management.

Multiphysics analysis of the dual role of magnetoelectric nanoparticles in a microvascular environment: from magnetic targeting to electrical activation.

Minimally invasive medical treatments for peripheral nerve stimulation are critically needed to minimize surgical risks, enhance the precision of therapeutic interventions, and reduce patient recovery time. Magnetoelectric nanoparticles (MENPs), known for their unique ability to respond to both magnetic and electric fields, offer promising potential for precision medicine due to their dual tunable functionality. In this study a multi-physics modeling of the MENPs was performed, assessing their capability to be targeted through external magnetic fields and become electrically activated. In particular, by integrating electromagnetic, fluid dynamics, and biological models, the efficacy of MENPs as wireless nano-tools to trigger electrical stimulation in the peripheral Nervous system present within the dermal microenvironment was assessed. The simulations replicate the blood venous capillary network, accounting for the complex interactions between MENPs, blood flow, and vessel walls. Results demonstrate the precise steering of MENPs (>95%) toward target sites under a low-intensity external magnetic field (78mT) even with a low susceptibility value (0.45). Furthermore, the extravasation and electrical activation of MENPs within the dermal tissue are analyzed, revealing the generation of high-induced electric fields in the surrounding area when MENPs are subjected to external magnetic fields. Overall, these findings predict that MENPs can be targeted in a tissue site when intravenously administrated, dragged through the microvessels of the venous system, and activated by generating high electric fields for the stimulation of the peripheral nervous system.

A 3D-printed multi-compartment organ-on-chip platform with a tubing-free pump models communication with the lymph node.

Multi-organ-on-chip systems (MOOCs) have the potential to mimic communication between organ systems and reveal mechanisms of health and disease. However, many existing MOOCs are challenging for non-experts to implement due to complex tubing, electronics, or pump mechanisms. In addition, few MOOCs have incorporated immune organs such as the lymph node (LN), limiting their applicability to model critical events such as vaccination. Here we developed a 3D-printed, user-friendly device and companion tubing-free impeller pump with the capacity to co-culture two or more tissue samples, including a LN, under a recirculating common media. Native tissue structure and immune function were incorporated by maintaining slices of murine LN tissue ex vivo in 3D-printed mesh supports for at least 24 h. In a two-compartment model of a LN and an upstream injection site in mock tissue, vaccination of the multi-compartment chip was similar to in vivo vaccination in terms of locations of antigen accumulation and acute changes in activation markers and gene expression in the LN. We anticipate that in the future, this flexible platform will enable models of multi-organ immune responses throughout the body.

An Antifreezing Scaffold-Based Cryopreservation Platform of Stem Cells for Convenient Application in Wound Repair.

Efficient cryopreservation of stem cells is crucial to fabricating off-the-shelf cell products for tissue engineering and regeneration medicine. However, it remains challenging due to utilization of toxic cryoprotectants for reducing ice-related cryodamages to stem cells during freeze-thaw cycle, stringent post-thaw washing process, and further integration of stem cells with scaffolds to form tissue engineering constructs for downstream applications. Herein, a novel cryopreservation platform of stem cells based on an antifreezing polyvinylpyrrolidone/gellan gum/gelatin (PGG) scaffold together is reported with an L-proline assisted cell pre-dehydration strategy. Results show that this platform is capable of inhibiting extra-/intracellular ice, thus can achieve high cryoprotection efficacy to stem cells (≈95%) without using any toxic cryoprotectants and eliminate traditional washing process. Meanwhile, the post-thawed stem cells can maintain their proliferation, differentiation, and paracrine functionalities. More importantly, due to the biocompatibility and three dimensional structure of the PGG scaffold, the post-thawed stem cell-laden PGG scaffold can be directly used as tissue engineering constructs for wound repair by mitigating inflammation and promoting collagen deposition at regenerating tissue sites. This present work demonstrates the feasibility of antifreezing scaffold-based cryopreservation platform of stem cells, which may advance the off-the-shelf stem cell-laden tissue engineering constructs for clinical translation.

Injectable nanocomposite hydrogels with co-delivery of oxygen and anticancer drugs for higher cell viability of healthy cells than cancer cells under normoxic and hypoxic conditions.

Injectable nanocomposite hydrogels (NC hydrogels) have the potential to be used for minimally invasive local drug delivery. In particular, pH-sensitive injectable NC hydrogels can be used in cancer treatment to deliver high doses of anticancer drugs to the target site in cancer tissue without damaging healthy tissue. Recent studies have shown that in addition to stimuli-responsive delivery of anticancer drugs to cancer cells, oxygen delivery to the hypoxic environment of cancer tissue can lead to advanced effects, as hypoxia and an acidic pH are common characteristics of cancer tissue. However, few studies have investigated the effects of simultaneous administration of oxygen (O2) and pH-dependent anticancer drugs via injectable NC hydrogels on the viability of healthy and cancer cells under normoxic and hypoxic conditions. In this context, we describe the synthesis of injectable NC hydrogels composed of pH-responsive nanomaterials carrying oxygen and anticancer drugs. Our system provides sustained O2 release and pH-responsive sustained release of anticancer drugs for 15 and 30 days, respectively. Moreover, O2 delivery and/or simultaneous delivery of O2 and anticancer drug resulted in higher cell survival of healthy fibroblast cells than malignant Colo-818 cells under hypoxic conditions (1% O2) after 7 days of incubation.&#xD.

Temperature-Dependent Cytokine Neutralization Induced by Magnetoelectric Nanoparticles: An In Silico Study.

Inflammatory cytokines cooperate to maintain normal immune homeostasis, performing both a protective and a pro-inflammatory action in different body districts. However, their excessive persistence or deregulated expression may degenerate into tissue chronic inflammatory status. Advanced therapies should be designed to deploy selective cytokine neutralizers in the affected tissues. Magnetoelectric nanoparticles (MENPs) possess unexploited potentialities, conjugating their ferromagnetic nature, which enables confinement in a specific tissue by directed positioning when subjected to low-intensity magnetic fields, with the capability to generate high electric fields with elevated spatial resolution when subjected to higher magnetic fields. This work proposes to exploit the extremely localized heat generated by Joule's effect around MENPs under an external magnetic field to denature a harmful cytokine in a hypothetical tissue site. An interdisciplinary and multiphysics in silico study was conducted to provide comprehensive modeling of the temperature distribution generated by MENPs decorated with a membrane-derived microvesicle (MV) coating designed to allocate a specific antibody to bind a target cytokine. A damage model was also implemented to provide an estimation of the influence of several design parameters on the cytokine denaturation efficacy, with the final goal of guiding the future development of effective MENPs-based therapeutic applications and strategies.

Surface-Enhanced Raman Scattering Nanoendoscope for Quantification of a Protein Released under Physiological Stimulation in Brain Tissue.

A surface-enhanced Raman scattering (SERS) biosensor with minimal invasiveness and high spatial resolution has been developed as a nanoendoscope to detect changes in protein concentrations at specific sites in biological tissues. While generally applicable to various tissues or proteins, the SERS nanoendoscope is demonstrated for the quantitative detection of S100β, an astrocytic protein whose plasmatic levels are known to vary in several neuropathologies such as Alzheimer's disease, schizophrenia, Down syndrome, Parkinson's disease and epilepsy, but for which intratissular levels have not been locally monitored, demonstrating key attributes of the SERS nanoendoscope. The SERS nanoendoscope is fabricated with densely and well-dispersed deposited gold nanoparticles modified with anti-S100β primary antibody on pulled optical fibers with a tip diameter of 700 nm, conducive to noninvasive and regiospecific detection of the S100β protein in different regions of mouse brain slices under different physiological stimuli with micrometer resolution. Quantification was performed ex vivo using SERS-active nanotags with secondary antibodies with detection limits of 5 and 7 nM in phosphate-buffered saline solution and mouse brain slice, respectively. Various physiological stimuli were then applied ex vivo to wild-type and S100β-knockout mouse brain slices to demonstrate the SERS nanoendoscope under physiological conditions. The average concentration of S100β was increased to 27, 45, and 48 nM upon N-methyl-d-aspartate, electrical, and optogenetic stimulation, respectively, statistically higher than all controls, demonstrating the ability of the SERS nanoendoscope to quantify protein release in biological tissues.

Spatial transcriptomics and in situ immune cell profiling of the host ectocervical landscape of HIV infected Kenyan sex working women.

Chronic immune activation is a hallmark of human immunodeficiency virus (HIV) infection that significantly impacts disease pathogenesis. However, in-depth studies characterizing the immunological landscape of the ectocervix during chronic HIV infection remain scarce despite the importance of this tissue site for HIV transmission. Ectocervical tissue samples were obtained from antiretroviral-naïve HIV-seropositive and -seronegative Kenyan female sex workers. These samples were assessed by spatial transcriptomics and Gene Set Enrichment Analysis. We further performed multi-epitope ligand cartography (MELC) using an in situ staining panel that included 17 markers of primarily T cell-mediated immune responses. Spatial transcriptomics revealed tissue-wide immune activation encompassing immune responses associated with chronic HIV infection. First, both the epithelial and submucosal compartments showed diverse but significant upregulation of humoral immune responses, as indicated by the expression of several antibody-related genes. Second, an antiviral state-associated cellular immunity was also observed in the HIV-seropositive group, characterized by upregulation of genes involved in interferon signaling across the mucosal tissue and a more spatially restricted mucosal expression of genes related to T cell activity and effector functions relative to the HIV-seronegative group. Additionally, HIV associated structural alterations were evident within both compartments. Downregulated genes across the epithelium were mainly linked to epithelial integrity, with the outer layer involved in terminal differentiation and the inner layer associated with epithelial structure. MELC analysis further revealed a significantly increased ectocervical leukocyte population in HIV-seropositive participants, primarily driven by an increase in CD8+ T cells while the CD4+ T cell population remained stable. Consistent with our spatial transcriptomics data, T cells from HIV-seropositive participants showed an increased effector phenotype, defined by elevated expression of various granzymes. By combining spatial transcriptomics and MELC, we identified significant HIV-associated cervical immune activity driven by induction of both T and B cell activity, together with a general antiviral state characterized by sustained interferon induction. These findings underscore that chronic HIV infection is associated with an altered ectocervical mucosal immune landscape years after primary infection. This sheds light on HIV pathogenesis at distant local sites and complements current knowledge on HIV-associated systemic immune activation.

Innovative approaches in stem cell therapy: revolutionizing cancer treatment and advancing neurobiology - a comprehensive review.

Stem cell therapy represents a transformative frontier in medical science, offering promising avenues for revolutionizing cancer treatment and advancing our understanding of neurobiology. This review explores innovative approaches in stem cell therapy that have the potential to reshape clinical practices and therapeutic outcomes in cancer and neurodegenerative diseases. In this dynamic and intriguing realm of cancer research, recent years witnessed a surge in attention toward understanding the intricate role of mesenchymal stem cells (MSCs). These cells, capable of either suppressing or promoting tumors across diverse experimental models, have been a focal point in the exploration of exosome-based therapies. Exosomes released by MSCs have played a pivotal role, in unraveling the nuances of paracrine signaling and its profound impact on cancer development. Recent studies have revealed the complex nature of MSC-derived exosomes, showcasing both protumor and antitumor effects. Despite their multifaceted involvement in tumor growth, these exosomes show significant promise in influencing both tumor development and chemosensitivity, acting as a pivotal factor that increases stem cells' potential for medicinal use. Endogenous MSCs, primarily originating from the bone marrow, exhibited a unique migratory response to damaged tissue sites. The genetic modification of stem cells, including MSCs, opened avenues for the precise delivery of therapeutic payloads in the milieu around the tumor (TME). Stem cell therapy offers groundbreaking potential for treating neurodegenerative and autoimmune disorders by regenerating damaged tissues and modulating immune responses. This approach aims to restore lost function and promote healing through targeted cellular interventions. In this review, we explored the molecular complexities of cancer and the potential for breakthroughs in personalized and targeted therapies. This analysis offers hope for transformative advancements in both cancer treatment and neurodegenerative disorders, highlighting the promise of precision medicine in addressing these challenging conditions.

Tissue-Specific DNA Methylation Changes in CD8+ T Cells During Chronic Simian Immunodeficiency Virus Infection of Infant Rhesus Macaques.

Robust CD8+ T cell responses are critical for the control of HIV infection in both adults and children. Our understanding of the mechanisms driving these responses is based largely on studies of cells circulating in peripheral blood in adults, but the regulation of CD8+ T cell responses in tissue sites is poorly understood, particularly in pediatric infections. DNA methylation is an epigenetic modification that regulates gene transcription. Hypermethylated gene promoters are associated with transcriptional silencing and, conversely, hypomethylated promoters indicate gene activation. In this study, we evaluated DNA methylation signatures of CD8+ T cells isolated from several different anatomic compartments during pediatric AIDS-virus infection by utilizing the SIVmac239/251 infected infant rhesus macaque model. We performed a stepwise methylation analysis starting with total cellular DNA, to immunomodulatory cytokine promoters, to specific CpG sites within the cytokine promoters in CD8+ T cells isolated from peripheral blood, lymph nodes, and intestinal tissue during the chronic phase of infection. Tissue-specific methylation patterns were determined for transcriptionally active promoters of key immunomodulatory cytokines: interferon gamma (IFNγ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNFα). In this study, we observed tissue-specific differences in CD8+ T cell modulation by DNA methylation in SIV-infected infant macaques, highlighting the importance of evaluating cells from both blood and tissues to obtain a complete picture of CD8+ T cell regulation during pediatric HIV infection.

TFE3 -rearranged Head and Neck Neoplasms : Twenty-two Cases Spanning the Morphologic Continuum Between Alveolar Soft Part Sarcoma and PEComa and Highlighting Genotypic Diversity.

TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3 -related neoplasms are rare in the head and neck and may pose diagnostic challenges. We herein describe 22 TFE3 fusion neoplasms affecting 11 males and 11 females aged 4 to 79 years (median, 25) and involving different head and neck sites: sinonasal cavities (n = 8), tongue (n = 4), oral cavity/oropharynx (n = 3), salivary glands (n = 2), orbit (n = 2), and soft tissue or unspecified sites (n = 3). Based on morphology and myomelanocytic immunophenotype, 10 tumors qualified as ASPS, 7 as PEComas (3 melanotic; all sinonasal), and 5 showed intermediate (indeterminate) histology overlapping with ASPS and PEComa. Immunohistochemistry for TFE3 was homogeneously strongly positive in all cases. Targeted RNA sequencing/FISH testing confirmed TFE3 fusions in 14 of 16 successfully tested cases (88%). ASPSCR1 was the most frequent fusion partner in ASPS (4 of 5 cases); one ASPS had a rare VCP::TFE3 fusion. The 6 successfully tested PEComas had known fusion partners as reported in renal cell carcinoma and PEComas ( NONO, PRCC, SFPQ , and PSPC1 ). The indeterminate tumors harbored ASPSCR1::TFE3 (n = 2) and U2AF2::TFE3 (n = 1) fusions, respectively. This large series devoted to TFE3-positive head and neck tumors illustrates the recently proposed morphologic overlap in the spectrum of TFE3 -associated mesenchymal neoplasms. While all PEComas were sinonasal, ASPS was never sinonasal and occurred in diverse head and neck sites with a predilection for the tongue. The indeterminate (PEComa-like) category is molecularly more akin to ASPS but shows different age, sex, and anatomic distribution compared with classic ASPS. We report VCP as a novel fusion partner in ASPS and PSPC1 as a novel TFE3 fusion partner in PEComa (detected in one PEComa). Future studies should shed light on the most appropriate terminological subtyping of these highly overlapping tumors.

A Review on Microengineering of Epithelial Barriers for Biomedical and Pharmaceutical Research.

Epithelial tissue forms a barrier around the human body and visceral organs, providing protection, permeation, sensation, and secretion. It is vital for our sustenance as it protects the tissue from harm and injury by restricting the entry of foreign bodies inside. Furthermore, it is a strong barrier to drugs, nutrients, and other essential deliverables. This layer also houses a large consortium of microbes, which thrive in tandem with human tissue, providing several health benefits. Moreover, the complex interplay of the microbiome with the barrier tissue is poorly understood. Therefore, replicating these barrier tissues on microdevices to generate physiological and pathophysiological models has been a huge interest for researchers over the last few decades. The artificially engineered reconstruction of these epithelial cellular barriers on microdevices could help underpin the host-microbe interaction, generating a physiological understanding of the tissue, tissue remodeling, receptor-based selective diffusion, drug testing, and others. In addition, these devices could reduce the burden of animal sacrifices for similar research and minimize the failure rate in drug discovery due to the use of primary human cells and others. This review discusses the nature of the epithelial barrier at different tissue sites, the recent developments in creating engineered barrier models, and their applications in pathophysiology, host-microbe interactions, drug discovery, and cytotoxicity. The review aims to provide know-how and knowledge behind engineered epithelial barrier tissue to bioengineers, biotechnologists, and scientists in allied fields.

Abstract IA020: Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer

Abstract Metastatic disease of prostate cancer (PCa) is currently incurable. Bone is the most common tissue site for prostate cancer metastasis and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone marrow neutrophils inhibit bone metastatic PCa growth, however metastatic PCa becomes resistant to neutrophil response and progresses within the bone compartment. It is unclear how these findings translate to a clinical setting. Further, the mechanisms associated with tumor resistance to neutrophil immune response remain unknown and presents a new avenue for therapeutic intervention. Thus, the goals of this study were: 1) to define the impact of metastatic PCa on neutrophil function throughout prostate cancer progression and 2) to determine the potential of neutrophils as predictive biomarkers of PCa disease progression. To do this, peripheral blood polymorphonuclear neutrophils (PMNs) were collected from 4 patient cohorts (localized PCa, metastatic hormone-sensitive PCa (mHSPC), metastatic castration-resistant (mCRPC) and healthy men) and PMN molecular and functional properties assessed, including: cancer cell cytotoxicity and cell surface markers. There was a significant decrease with disease progression in PMN expression of CD10, a marker for differentiation, while in tandem, there was an increase in pro-inflammatory marker, CD88 (complement receptor) in mCRPC men compared to mHSPC. PMNs from all disease stages were equally cytotoxic to human PCa cell lines (LNCaP, C42B, and PC3). However, second generation androgen deprivation therapy (ADT) suppressed patient PMN cytotoxicity against mCRPC cells (C42B, PC3). This suppression was due to androgen receptor (AR)-mediated regulation of the pleotropic and immune suppressant cytokine, transforming growth factor beta receptor I (TβRI). PMNs from mCRPC patients who received 2nd generation ADT, expressed significantly more TβRI than patients who only received 1st line ADT. Further, we found that PMNs in CRPC patient bone metastases express more TβRI than PMNs in matched liver metastases, which express little to no TβRI. Treatment of mouse bone marrow neutrophils with enzalutamide, increased neutrophil TβRI expression in a dose dependent manner and blocked cytotoxicity against PCa cells. Exogenous testosterone treatment in vivo, pharmacologic inhibition (using Repsox, a small molecule kinase inhibitor of TβRI) or genetic deletion (using conditional TβRI knockout mice) rescued enzalutamide-mediated neutrophil suppression and restored neutrophil cytotoxicity. These data collectively suggest that AR inhibition suppresses anti-tumor neutrophil responses via TβRI however, this study highlights the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa. Citation Format: Leah M Cook. Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA020.

Exploring mesenchymal stem cells homing mechanisms and improvement strategies.

Mesenchymal stem cells (MSCs) are multipotent cells with high self-renewal and multilineage differentiation abilities, playing an important role in tissue healing. Recent advancements in stem cell-based technologies have offered new and promising therapeutic options in regenerative medicine. Upon tissue damage, MSCs are immediately mobilized from the bone marrow and move to the injury site via blood circulation. Notably, allogenically transplanted MSCs can also home to the damaged tissue site. Therefore, MSCs hold great therapeutic potential for curing various diseases. However, one major obstacle to this approach is attracting MSCs specifically to the injury site following systemic administration. In this review, we describe the molecular pathways governing the homing mechanism of MSCs and various strategies for improving this process, including targeted stem cell administration, target tissue modification, in vitro priming, cell surface engineering, genetic modifications, and magnetic guidance. These strategies are crucial for directing MSCs precisely to the injury site and, consequently, enhancing their migration and local tissue repair properties. Specifically, our review provides a guide to improving the therapeutic efficacy of clinical applications of MSCs through optimized in vivo administration and homing capacities.

Feasibility Study of Label-Free Raman Spectroscopy forParathyroid Gland Identification.

We aim to evaluate the feasibility of Raman spectroscopy for parathyroid gland (PG) identification during thyroidectomy. Using a novel side-viewing handheld Raman probe, a total of 324 Raman spectra of four tissue types (i.e., thyroid, lymph node, PG, and lipid) commonly encountered during thyroidectomy were rapidly (< 3 s) acquired from 80 tissue sites (thyroid [n = 10], lymph node [n = 10], PG [n = 40], lipid [n = 20]) of 10 euthanized Wistar rats. Two partial least-squares (PLS)-discriminant analysis (DA) detection models were developed, differentiating the lipid and nonlipid (i.e., thyroid, lymph node, and PG) tissues with an accuracy of 100%, and PG, lymph node, and thyroid could be detected with an accuracy of 98.4%, 93.9%, and 95.4% respectively. This work demonstrates the feasibility of Raman spectroscopy technique for PG identification and protection during thyroidectomy at the molecular level.

Differences in the pathological, transcriptomic, and prognostic implications of lymphoid structures between primary and metastatic cutaneous melanomas

BackgroundWhile the prognostic role of tertiary lymphoid structures (TLS) has been well studied in solid cancers, the prevalence and impact of immature precursor lymphoid structures known as lymphoid aggregates (LA)...

Retroperitoneal Myoepithelial Carcinoma with Heterologous Bone Formation and EWSR1::ZNF444

Abstract Introduction/Objective Soft tissue myoepithelial tumors are rare tumors that affect a wide age range and diverse tissue sites. Fewer than five cases have been reported in the retroperitoneum. Most tumors are benign with the only histologic criterion for malignancy being cytologic atypia. The morphology is broad ranging from spindled to epithelioid cells of varying cellularity in sclerotic to myxoid stroma. Heterologous differentiation may be present. These tumors usually express cytokeratin, EMA, S100, and GFAP and show EWSR1 and FUS rearrangements. Here we present an unusual case of retroperitoneal myoepithelial carcinoma. Methods/Case Report A 29-year-old female presented with rash and painless jaundice. CT and MRCP revealed a relatively circumscribed 3.7 cm mass in the porta hepatis. On fine needle aspiration, a possible gastrointestinal stromal tumor was considered due to DOG1 expression. The patient underwent a Whipple procedure with negative margins showing tumor in soft tissue adjacent to the common bile duct. The tumor was multinodular and consisted predominantly of mild to moderately pleomorphic epithelioid cells in fibromyxoid stroma with interspersed woven bone. Mitoses were not appreciated, and necrosis not seen. The tumor was focally positive for CK AE1/AE3, GFAP, and DOG1 and negative for S100, SOX10, p63, and CD117. INI1 was retained. NGS identified EWSR1::ZNF44 and a diagnosis of myoepithelial carcinoma was rendered. The patient received no adjuvant therapy and has not shown any evidence of metastasis or recurrence for 17 months. Results (if a Case Study enter NA) NA Conclusion Soft tissue myoepithelial carcinomas are aggressive tumors with approximately 40% recurrence and over 50% metastasis. Standard treatment is complete surgical resection. The efficacy of radiation and chemotherapy is not clear. EWSR1 fusions with various partners including POU5F1, PBX1/3, and ZNF44 have been identified. Due to their rarity and varying histology and immunohistochemical expression, identification of gene fusions can be invaluable in diagnosing soft tissue myoepithelial tumors, especially in unusual locations.