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Extramedullary disease in multiple myeloma.

When clonal plasma cells grow at anatomic sites distant from the bone marrow or grows contiguous from osseous lesions that break through the cortical bone, it is referred to as extramedullary multiple myeloma (EMD). EMD remains challenging from a therapeutic and biological perspective. The pathogenetic mechanisms are not completely understood and it is generally associated with high-risk cytogenetics which portends poor outcomes. There is a rising incidence of EMD in the era of novel agents, likely a reflection of longer OS, with no standard treatment approach. Patients benefit from aggressive

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… It was hypothesized that specific tropism or homing of EMM clones makes them more prone to trafficking to these sites. Fig. 1 Pathogenesis of extramedullary spread in multiple myeloma. …

Viral Respiratory Infections in Hematological Patients.

Viral infections of the respiratory system represent one of the most important complications in hematological patients in terms of both the severity of the clinical picture and its related impact on the duration of hospitalization, and of mortality. The most implicated viruses are those that commonly cause community-based respiratory diseases: respiratory syncytial virus, Influenza virus and rhinovirus. However, in some cases the clinical picture may be triggered by first infection with or reactivation of pathogens normally not responsible for clinically relevant diseases in immunocompetent su

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… The various serotypes can be associated with different clinical manifestations according to different receptor tropisms in different tissues [ 6 ]. Bocavirus (hBoV) is a small DNA virus belonging to the Parvoviridae family [ 6 ]. …

A Comprehensive Review of Modern Cancer Therapies Utilizing Oncolytic Viruses.

Oncolytic viruses (OVs) are gaining traction as advanced tools in cancer therapy. They are distinguished by their ability to destroy malignant cells while sparing normal tissue specifically. In addition to their direct tumor-lysing properties, an essential benefit of oncolytic virus therapy is its capacity to activate both the innate and adaptive immune systems. To enhance these therapeutic actions, many OVs have been genetically engineered to encode immune-modulating factors that reestablish or strengthen antitumor immune responses. Recent studies show that combining OVs with other forms of i

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… The virus’s fiber protein has been modified by substituting its original heparan sulfate glycosaminoglycan-binding motif with an integrin-recognizing sequence, enhancing its affinity for cancer cells while minimizing liver cell tropism. … Strategies include advanced genetic engineering, enhancing tropism for metastatic or microenvironment-specific cells (e.g., by introducing ligands for receptors overexpressed in metastases), and novel therapeutic combinations involving checkpoint inhibitors, CAR-T technologies, or other immune-modulating …

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents.

The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian

Evaluation of epidemiological and pathological features of symptomatic spinal metastases in Romania - what could we learn from a retrospective study?

Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SMs) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SMs surgically treated in the Neurosurgery Clinics of a Regional Hospital in North-Eastern Romania over a period of five years, in order to define a certain tumor profile that would benefit from an early screening. We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor chara

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… It is well known that this type of neoplasia presents a particular tropism for BM. In 2007, approximately 350 000 patients were diagnosed with BMs in the United States [ 29 ]. …

Multidisciplinary supportive care in systemic light chain amyloidosis.

The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidat

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… First, amyloid fibrils’ avidity for the transplanted organs is lower compared to the previous tropism for the native kidney [ 40 ]. …

Targeting the BMP Pathway in Prostate Cancer Induced Bone Disease.

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient's current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ)

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… A Humanized Orthotopic Tumor Microenvironment Alters the Bone Metastatic Tropism of Prostate Cancer Cells. Commun Biol (2021) 4(1):1014. doi: 10.1038/s42003-021-02527-x 42. Liu Y, Zhang RX, Yuan W, Chen HQ, Tian DD, Li H, et al. …

Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies.

BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay. The primary outcome was the proport

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… The synthetic peptides of the VirScan library span the reference protein sequences (collapsed to 90% identity) of all viruses annotated to have human tropism in the UniProt database (244 species, 119,233 epitopes) as well as full-length proteins of 62 bacterial species (2986 epitopes) identified from …

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages. Nevertheless, the clinical results in terms of overall survival and progression free survival were not as anticipated. Majority of cancer patients do not respond to immunotherapies and the reasons differ. Hence, further improvements for cancer immunotherapies are cruc

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… Other than expressing adequate levels of immunomodulatory molecules, the oncolytic tropism of the virus may help in circumventing toxicity issues by limiting expression in the tumor microenvironment with minimal leakage to the periphery. FIGURE 8 Enhancing oncolytic adenoviral therapy. … One of the reasons is that oncolytic viruses have been generally seen as direct tools for killing cancer due to their tumor-specific tropism. …

Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies.

Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm

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… It has been described that BM-MSCs show a strong tropism towards injured tissues because the intravenous delivery of BM-MSCs results in their migration to specific sites of injury. … Due to their tropism to inflammatory sites, the chemotactic responses of MSCs are generally considered to resemble those of immune cells. …

Current State of Knowledge on Primary Sjögren's Syndrome, an Autoimmune Exocrinopathy.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3-3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the saliv

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… EBV is a double stranded DNA virus appertaining to Herpesviridae family, with a strong tropism for B cells. EBV has often been associated with autoimmunity processes and diseases such as Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Multiple Sclerosis (MS) [ 14 , 15 ]. … Clinical Manifestations Although often reduced to its sicca syndrome due to its tropism for glandular tissue, pSS remains a systemic disease that can affect virtually all organs. …

Hemophagocytic Lymphohistiocytosis (HLH) in Patients with Tick-Borne Illness: A Scoping Review of 98 Cases.

Hemophagocytic lymphohistiocytosis (HLH) secondary to tick-borne infections is a rare but potentially life-threatening syndrome. We performed a scoping review according to PRISMA guidelines to systematically analyze the existing literature on the topic. A total of 98 patients were included, with a mean age of 43.7 years, of which 64% were men. Most cases, 31%, were reported from the USA. Immunosuppression was present in 21.4%, with the most common cause being previous solid organ transplantation. Constitutional symptoms were the most common, observed in 83.7% of the patients, while fever was r

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… The pathogen isolated in this case was Rickettsia conorrii , which has previously been shown to be associated with fulminant purpura and small vessel vasculitis due to its tropism for endothelial cells [ 107 ]. …

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review.

PurposeBone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis.MethodsA comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analys

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… These findings suggest that the expression levels of S100A9/A8 may be critical for bone tropism in certain lung cancers. The elevated expression of S100A8/9 in SBC5 could play a role in the crosstalk between lung cancer cells and BMAs. …

CAR-Engineered Cell Therapies Beyond Cancer: Reprogramming Fibrosis and Immune-Mediated Inflammation.

Chimeric antigen receptor (CAR)-engineered cell therapies are being extended from hematological malignancies to autoimmune, inflammatory, and fibrotic diseases, although the maturity of evidence differs markedly among platforms and indications. Early clinical evidence from case reports, small case series, and early-phase trials suggests that CD19- or BCMA-directed CAR-T cells can induce deep B-cell or plasma-cell depletion and sustained remission in selected patients with refractory autoimmune diseases; however, their comparative efficacy, durability, and long-term safety remain incompletely d

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… Selected subsets exhibit restricted alloreactivity, tissue tropism, and innate‐like responses that may support allogeneic product development and provide advantages in diseases characterized by tissue‐localized inflammation or fibrosis. …

Nanotechnology-Driven Cancer Therapies for Precision Oncology: Advances and Clinical Outlook.

Cancer continues to pose a global health challenge, with conventional therapies often limited by non-specific toxicity, drug resistance, and an inadequate therapeutic index. Nanotechnology offers transformative opportunities by enabling targeted drug delivery, improved pharmacokinetics, and integrated diagnostic-therapeutic platforms (termed nanotheranostics). This review highlights key nanocarrier systems including liposomes, polymeric nanoparticles, dendrimers, inorganic nanostructures, carbon-based materials, extracellular vesicles, and hybrid platforms with a focus on human studies and cli

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… Stimuli-responsive platforms tuned to the tumor microenvironment (pH, enzymes, hypoxia, etc.) allow for adaptive drug release across variable intratumoral niches. 84 Biomimetic coatings (platelet, cancer-cell, or macrophage membranes) enhance immune evasion and broad tumor tropism, improving intratumoral … Hitchhiking NPs (such as macrophage-hitchhiking NPs) take advantage of the natural tropism of macrophages to immunologically privileged hypoxic tumor sites. 108 Glioblastoma and triple-negative breast cancer preclinical tumor models have demonstrated that macrophages loaded ex vivo with iron oxide or …

CAR T cells: engineered immune cells to treat brain cancers and beyond.

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential t

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… Tumor tropism of adoptively transplanted T lymphocytes by controlling tumor chemokine release to glioblastoma expressing CCL2, (a ligand for CCR4) has been demonstrated [ 64 , 65 ]. … Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells. J Immunol. 2007;179(5):3332–3341. doi: 10.4049/jimmunol.179.5.3332. 65. Vitanza NA, Johnson AJ, Wilson AL, Brown C, Yokoyama JK, Künkele A, et al. …

Current landscape of gene-editing technology in biomedicine: Applications, advantages, challenges, and perspectives.

The expanding genome editing toolbox has revolutionized life science research ranging from the bench to the bedside. These "molecular scissors" have offered us unprecedented abilities to manipulate nucleic acid sequences precisely in living cells from diverse species. Continued advances in genome editing exponentially broaden our knowledge of human genetics, epigenetics, molecular biology, and pathology. Currently, gene editing-mediated therapies have led to impressive responses in patients with hematological diseases, including sickle cell disease and thalassemia. With the discovery of more e

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… have been applied to deliver gene‐editing components into target cells of interest. 144 , 224 , 225 , 226 Most currently, AAVs and lentiviruses, depending on some unique advantages, have been widely used in clinical trials. 227 , 228 , 229 Natural AAV vectors have 11 serotypes, which possess inherent tropisms … for different tissues. 227 Because of the tropism for the eye, AAV2 has been approved by the FDA for treating degenerative retinal disorders. 230 , 231 Moreover, AAV vectors could reduce the risk of genomic mutation because the gene cargos carried by AAV cannot integrate into the host genome. …

Glioblastoma Treatment: State-of-the-Art and Future Perspectives.

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Recently, bevacizumab has been added to the treatment arsenal for the recurrent scenario. Nevertheless, patients with glioblastoma still have a poor prognosis. Therefore, many efforts are being made in different clinical research areas to find a new alternative to improve ove

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… The cellular tropism of human adenoviruses (HAd) differs between the different serotypes. Adenovirus serotype 5 (AD5) is a conditionally replicating adenovirus (CRad) and is the most widely used for gene delivery and the most studied [ 74 , 75 ]. … Furthermore, the upregulation of CD155/PVR has been demonstrated in GB samples, which may explain the particular tropism of an attenuated poliovirus strain (Sabin) for glioma cells [ 74 ]. …

Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK).

Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition t

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… However, the different forms of amyloid show different organ tropism typical for the respective disease. Systemic forms of amyloidosis affecting the heart, are mainly AL, ATTRwt, and some forms of ATTRv amyloidosis. … However, the different types of amyloid show different organ tropism typical for the respective disease. …

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

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… Seneca Valley Virus | · The selective tropism of virus replication may involve receptor-mediated internalization [ 158 – 160 ]. | · Preclinical data in SCLC: complete and durable responses with systemic administration [ 161 ]; preexisting antibodies are rare. … Seneca valley virus (SVV-001) Upon infection, this agent replicates intracellularly, resulting in tumor cell lysis and reduced tumor cell proliferation; the selective tropism of virus replication may involve receptor-mediated internalization [ 158 – 160 ]. …