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Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis.

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expre

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… Moreover, HuR has been reported to regulate the expression of parathyroid hormone-related protein, a key osteolytic factor, in human cancer cells with bone tropism 24 , 25 . However, the role of HuR in breast cancer bone metastasis remains unclear. … bone metastasis of breast cancer cells To determine whether the expression of HuR, an RNA-binding post-transcriptional regulator, is essential for breast cancer bone metastasis, we used an MDA-MB-231 basal-like/triple-negative human breast cancer cell line that has exhibited well-characterized bone tropism …

Изучение точных методов лечения иммунизированных подстрекательских заболеваний: использование бесконечного потенциала доставки нуклеиновой кислоты.

Неизлечимые подстрекательские заболевания (ИМИД) создают неизмеримое бремя для отдельных лиц и общества. В то время как традиционное использование иммунодепрессантов и лекарственных средств для борьбы с заболеваниями обеспечивает частичную помощь и контроль, их неизбежные побочные эффекты и ограниченная эффективность ставят под сомнение возможность найти лекарство. Перспективные лекарства от нуклеиновой кислоты продемонстрировали способность оказывать точное воздействие на молекулярном уровне, при этом различные классы нуклеиновых кислот выполняют регулирующие функции с помощью различных механ

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… The protein capsid and/or envelope surround the genetic payload, determining the vector's host tissue or cell tropism and antigen recognition. When expressed in cells, the transgene imparts the desired effect. … AAVs encompass 11 natural serotypes and over 100 variants. [ 71 ] Each serotype exhibits tropism towards a specific tissue, making it suitable for delivering genes to a specific organ. …

Exosomes and organ-specific metastasis.

The transmission of information between tumor cells and other cell types in the tumor microenvironment plays an important role in tumor meta … on exosomes that can locate metastatic cells at the initial stage of metastasis and show good organotropism. This fact suggests that a clear understanding of the roles of exosomal integrins will be beneficial for future clinical applications. Follow-up studies on exosomes using continuously updated purification techniques and identification methods are ex …

Secondary renal amyloidosis due to primary Sjogren's syndrome: a case report.

UNLABELLED: Amyloidosis is a rare disorder characterized by the deposition of abnormal proteins in extracellular tissues, resulting in the dysfunction of vital organs and, eventually, death. The occurrence of amyloidosis due to primary Sjogren's syndrome (pSS) is a rare finding. This study describes a rare case of pSS complicated by amyloid-associated amyloidosis. CASE PRESENTATION: A 35-year-old male was diagnosed with nephrotic syndrome and secondary amyloidosis caused by pSS. He had microscopic hematuria, a creatinine level of 6.59 mg/dl, and an elevated erythrocyte sedimentation rate of 1

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… Although many autoantigens are shared between SS and systemic lupus erythematosus, the inflammatory tropism at the glands in pSS may account for the differential pathogenic mechanism. Nevertheless, the molecular explanation for this phenomenon is still unknown. …

Surgical Roles for Spinal Involvement of Hematological Malignancies.

ObjectivePatients with hematological malignancies frequently encounter spine-related symptoms, which are caused by disease itself or process of treatment. However, there is still lack of knowledge on their epidemiology and clinical courses. The purpose of this article is to review clinical presentations and surgical results for spinal involvement of hematologic malignancies.MethodsFrom January 2011 to September 2014, 195 patients (98 males and 97 females) suffering from hematological malignancies combined with spinal problems were retrospectively analyzed for clinical and radiological characte

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… Because authors had not examined MRI of non-symptomatic patients with hematologic malignancies, it is unclear whether hematologic malignancies have some tropism. …

Bispecific antibodies and nanotechnology: a strategic alliance in cancer immunotherapy.

Bispecific antibodies (bsAbs), designed to recognize two distinct antigens or epitopes, enable innovative mechanisms of action for emerging generations of cancer immunotherapies. Despite their potential, bsAb therapeutics face several challenges related to their biodistribution and pharmacokinetics, which often result in a suboptimal efficacy/toxicity balance. Starting with a brief description of the relevance of bsAbs in cancer immunotherapy, this review aims to critically analyze the synergistic potential of nanotechnology and bsAb technology oriented to enhance therapeutic efficiency while

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… This implies that their primary functional tropism towards the liver is not of concern, as virtually any cell may function as production and secretion center. … Enhancement of tumor tropism of mPEGylated nanoparticles by anti-mPEG bispecific antibody for ovarian cancer therapy. Sci Rep. 2021;11:7598. 10.1038/s41598-021-87271-2. 33828191 10.1038/s41598-021-87271-2 PMC8027450 21. …

Understanding Mesangial Pathobiology in AL-Amyloidosis and Monoclonal Ig Light Chain Deposition Disease.

Patients with plasma cell dyscrasias produce free abnormal monoclonal Ig light chains that circulate in the blood stream. Some of them, termed glomerulopathic light chains, interact with the mesangial cells and trigger, in a manner dependent of their structural and physicochemical properties, a sequence of pathological events that results in either light chain-derived (AL) amyloidosis (AL-Am) or light chain deposition disease (LCDD). The mesangial cells play a key role in the pathogenesis of both diseases. The interaction with the pathogenic light chain elicits specific cellular processes, whi

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… generate a diverse repertoire of polyclonal antibodies. 39 61 Contribution of the V L Gene Segment to LC Aggregation There is evidence that the V L gene segment that encodes the LC influences its propensity to form amyloid, as well as the tendency to predominantly deposit in certain organs (organ tropism … It was also reported that the κ1 gene IGKV1-33 confers organ tropism to the LCs, because the LCs derived from it are more likely to cause liver involvement than the others. 62 , 63 , 65 What makes LC derived from AL-associated V L genes prone to deposition as amyloid has not yet been elucidated. …

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets.

Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient's own immune system to selectively kill cancer cells. The immune system is the body's main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recogni

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… Therefore, viruses, with a natural tropism, are able to effectively infect these highly replicative cells. Another benefit of these agents is insertion of therapeutic genes in their viral genome, so that an anti-tumour immunity can be strongly induced [ 162 ]. … The lack of E1B dictates the tumour tropism feature, limiting infectivity to cells that provide RNA export, which is not found in normal cells [ 175 ]. …

Долговременная ремиссия CNS с эгранатамабом и внутритехологическая терапия в многократной миеломе.

Участие центральной нервной системы (ЦНС) в множестве миеломы (ММ) является редким, но разрушительным осложнением, связанным с плохим прогнозом и ограниченными терапевтическими возможностями. Мы сообщаем о 73-летней женщине с повышенным риском иг-каппой MM, которая прятала TP53 [del(17p)] и 13q, у которой появились внематочные и CNS болезни после шести предыдущих линий терапии, включая две аутологические трансплантации стволовых клеток, и которая была трехклассной рефракторной до протеозных ингибиторов, иммуномодуляторных агентов и антиCD38 моноклонных антител. При рецидиве CNS цитология цереб

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… High-risk cytogenetic abnormalities, particularly TP53 deletion [del(17p)] and 13q deletion, are well-recognized drivers of genomic instability and are strongly associated with extramedullary dissemination, CNS tropism, and early relapse [ 4 , 5 ]. …

Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.

Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectivene

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… Tumor cells rapidly recruit and become cloaked by platelets during intravasation, protecting circulating tumor cells from shear stress and immune clearance while creating a natural tropism mediated by receptor–ligand interactions such as P-selectin–PSGL-1/CD24 and integrin αIIbβ3/GPIb. …

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

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… Notably, many mutations in the TTR gene lead to multisystemic involvement and influence the tropism of specific organs. … Developing integrated, modular models to capture these genetic and molecular interactions may improve understanding of tropism and enable precision diagnosis and personalized therapy in ATTR amyloidosis [ 63 ]. …

Gamma/delta T cells as cellular vehicles for anti-tumor immunity.

Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied in these therapies have proven efficacy but are confined almost exclusively to autologous use. When infused into patients with mismatched human leukocyte antigen, αβ T cells recognize tissues of such patients as foreign and elicit devastating graft-versus-host disease. Therefore, one way to overcome this challenge is to use naturally allogeneic immune cell typ

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… Other features not illustrated in the diagram include tissue tropism of certain, e.g. Vδ1, γδ T cell subsets and the reduced possibility of CRS, presumably leading to better infiltration of TME and improved safety. … It is thought that such tissue tropism may enhance the capacity of γδ T cell subtypes to infiltrate the TME of diverse solid tumors consisting tissues which are the physiological habitats for the respective cell subtypes. …

Radiation therapy for secondary cutaneous plasmacytomas.

We are reporting a case of a 75-year-old man with multiply recurrent IgA-lambda multiple myeloma status post multiple rounds of chemotherapy, autologous stem cell transplantation, and palliative radiation therapy for diffuse bone lesions. Approximately 15 years after original diagnosis, he developed secondary cutaneous plasmacytomas of the right arm, right chest wall, and right upper back over the course of several months. He underwent palliative involved field 3D conformal photon or en face electron therapy concurrently with various chemotherapy regimens and achieved good to complete response

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… Gisselbrecht M Unusual presentation of myeloma in an elderly woman: breast and cutaneous involvement European Journal of Internal Medicine 2008 19 2 150 151 2-s2.0-38749107780 10.1016/j.ejim.2007.06.004 18249318 12 Pereira MA Baudrier T Costa A Magalhães J Azevedo F Cutaneous metastatic plasmacytomas with tropism …

Diffuse Bone Marrow Metastasis as the Initial Presentation of an Occult Breast Cancer.

IntroductionBreast cancer is one of the malignancies which tend to involve the bone marrow, but initial presentation with diffuse bone marrow metastasis from an occult breast cancer is very rare. Prognosis is generally very poor for marrow metastasis from solid tumors except that breast cancer is a treatable disease even in such a dismal condition.CaseA 64-year-old woman's headache was found to result from diffuse adenocarcinoma metastasis in the bone marrow from an unknown primary site. Intensive immunohistochemistry study of bone marrow biopsy specimen confirmed the disease nature to be an e

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… Seeding into bone marrow and resulting in bony metastasis need not only RANK-RANKL pathway but also many other biologic targeting and stimulating molecules to establish an ample bone-specific tropism, fuel osteolysis, osteoblastogenesis, and T-cell differentiation [ 17 ]. …

Extracellular Vesicles in Chronic Lymphocytic Leukemia: Tumor Microenvironment Messengers as a Basis for New Targeted Therapies?

In addition to intrinsic genomic and nongenomic alterations, tumor progression is also dependent on the tumor microenvironment (TME, mainly composed of the extracellular matrix (ECM), secreted factors, and bystander immune and stromal cells). In chronic lymphocytic leukemia (CLL), B cells have a defect in cell death; contact with the TME in secondary lymphoid organs dramatically increases the B cells' survival via the activation of various molecular pathways, including the B cell receptor and CD40 signaling. Conversely, CLL cells increase the permissiveness of the TME by inducing changes in th

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… One can also imagine that therapeutic EVs containing vesiculation inhibitors could be optimized for the delivery to CLL cells through the expression of specific tumor surface proteins and/or their production in mesenchymal stem cells that display a natural tropism toward tumor cells. … EBV-Gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL PLoS ONE 2011 6 e25294 10.1371/journal.pone.0025294 22022385 PMC3189918 90. Gärtner K. Luckner M. Wanner G. Zeidler R. …

Al amyloidosis.

UNLABELLED: DEFINITION OF THE DISEASE: AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC,

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… Several characteristics indicate that LC primary structure are involved in the propensity to form amyloid, including the overrepresentation of lambda LC (2 to 4 times more frequent than kappa LC), and the association of homology family of LC V region with organ tropism. … Invernizzi R Perlini S Klersy C Merlini G The repertoire of λ light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44 Blood 2012 119 144 150 10.1182/blood-2011-05-355784 22067386 Comenzo RL Zhang Y Martinez C Osman K Herrera GA The tropism …

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identify

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… Interestingly, herpes viruses have a natural tropism for neuronal cells, making them suitable vectors for gliomas and glioblastomas [ 132 – 135 ]. … Nonreplicating adenoviral vectors: improving tropism and delivery of cancer gene therapy. Cancers. 2021;13(8):1863. 95. Sato-Dahlman M, Yamamoto M. The development of oncolytic adenovirus therapy in the past and future–for the case of pancreatic cancer. …

Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following th

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… Glioma tumour cells were concurrently irradiated, which allowed radiation-induced tropism of NPs towards chemokine (CC motif) ligand 2 (CCL2). … After irradiating the glioma tumour cells, the NPs could be directed toward the chemokine (CC motif) ligand 2 (CCL2), which is greatly expressed through radiation-induced tropism. …

AL Amyloidosis: Current Chemotherapy and Immune Therapy Treatment Strategies: JACC: CardioOncology State-of-the-Art Review.

Immunoglobulin light chain (AL) amyloidosis is an incurable plasma cell disorder characterized by deposition of fibrils of misfolded immunoglobulin free light chains (FLC) in target organs, leading to failure. Cardiac involvement is common in AL amyloidosis and represents the single most adverse prognostic feature. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to arrest the process of amyloid deposition and preserve organ function. The clinical use of molecularly targeted drugs, such as protea

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… The identity of the precursor protein distinguishes the various amyloidoses and guides organ tropism and the therapeutic approach ( 1 ). … Amyloidogenic FLC are skewed toward λ Ig light chain (about 75% of cases), and specific Ig light chain genotypes are associated with particular organ tropism ( 3 ). …

Light Chain Amyloidosis.

Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy. The specific treatment is chemotherapy targe

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… The light chain variable region gene and the gene family of the clone can, at least in part, explain the variable organ tropism of AL amyloidosis. … Oliva L Orfanelli U Resnati M The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity Blood 2017 129 15 2132 2142 https://doi.org/10.1182/blood-2016-08-730978 28130214 10.1182/blood-2016-08-730978 17 Comenzo R Zhang Y Martinez C Osman K Herrera G The tropism …