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T-Cell Lymphoma With Sarcoid-Like Reaction and Secondary Myelofibrosis: A Unique Case Report and Literature Review.

INTRODUCTION: T-cell lymphomas are rare, comprising 10%-15% of non-Hodgkin lymphomas (NHLs). Their etiology remains unclear, and pathophysiology varies widely among subtypes. Sarcoid-like reactions (SLRs) have been reported in approximately 7.3% of NHLs, including T-cell lymphomas, and can closely resemble sarcoidosis clinically/histologically. This overlap complicates diagnosis, particularly when secondary myelofibrosis-a rare and poorly understood complication-arises. Myelofibrosis has also been observed in sarcoidosis, further blurring the distinction between these entities. Treatment for T

Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making.

Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confir

Clinical relevance of extracellular vesicles in hematological neoplasms: from liquid biopsy to cell biopsy.

In the era of precision medicine, liquid biopsy is becoming increasingly important in oncology. It consists in the isolation and analysis of tumor-derived biomarkers, including extracellular vesicles (EVs), in body fluids. EVs are lipid bilayer-enclosed particles, heterogeneous in size and molecular composition, released from both normal and neoplastic cells. In tumor context, EVs are valuable carriers of cancer information; in fact, their amount, phenotype and molecular cargo, including proteins, lipids, metabolites and nucleic acids, mirror nature and origin of parental cells rendering EVs a

Nitrogen containing bisphosphonates associated osteonecrosis of the jaws: A review for past 10 year literature.

Nitrogen containing bisphosphonate (N-BP) therapy is used extensively to treat osteoporosis and osteolytic bone lesions. Recently, a special form of osteonecrosis limited to the maxillofacial skeleton has been discovered especially within those patients who are receiving either long-term N-BP therapy alone and/or associated with invasive dental procedure. Bisphosphonates accumulate almost exclusively in maxillofacial skeleton owing to high bone turn over remodeling to maintain the mechanical competence. The pathogenesis and why it commonly appears in maxillofacial skeleton and the fixed treatm

SOX9 Induces Orbital Fibroblast Activation in Thyroid Eye Disease Via MAPK/ERK1/2 Pathway.

PurposeTo evaluate the expression of sry-box transcription factor 9 (SOX9) in orbital fibroblasts (OFs) of thyroid eye disease (TED) and to find its potential role and underlying mechanism in orbital fibrosis.MethodsOFs were cultured from orbital connective tissues obtained from patients with TED (n = 10) and healthy controls (n = 6). SOX9 was depleted by small interfering RNA or overexpressed through lentivirus transduction in OFs. Fibroblast contractile activity was measured by collagen gel contraction assay and proliferation was examined by EdU assay. Transcriptomic changes were assessed by

Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types.

For the treatment of postmenopausal osteoporosis, several drug classes with different mechanisms of action are available. Since only a limited set of dosing regimens and drug combinations can be tested in clinical trials, it is currently unclear whether common medication strategies achieve optimal bone mineral density gains or are outperformed by alternative dosing schemes and combination therapies that have not been explored so far. Here, we develop a mathematical framework of drug interventions for postmenopausal osteoporosis that unifies fundamental mechanisms of bone remodeling and the mec

The Impact of Immune System in Regulating Bone Metastasis Formation by Osteotropic Tumors.

Bone metastases are frequent and debilitating consequence for many tumors, such as breast, lung, prostate, and kidney cancer. Many studies report the importance of the immune system in the pathogenesis of bone metastasis. Indeed, bone and immune system are strictly linked to each other because bone regulates the hematopoietic stem cells from which all cells of the immune system derive, and many immunoregulatory cytokines influence the fate of bone cells. Furthermore, both cytokines and factors produced by immune and bone cells promote the growth of tumor cells in bone, contributing to supporti

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

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chroni

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… Integrins and the activation of latent transforming growth factor beta1—An intimate relationship. Eur. J. Cell Biol. 2008;87:601–615. doi: 10.1016/j.ejcb.2008.01.012. 110. Verrecchia F., Mauviel A. … Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma. Cancer Res. 2001;61:550–555. 121. Walker R.A. The complexities of breast cancer desmoplasia. Breast Cancer Res. 2001;3:143–145. doi: 10.1186/bcr287. 122. …

The therapeutic effect of modified Huangqi Guizhi Wuwu Tang for multiple myeloma: An 18-year follow-up case report.

RationaleMultiple myeloma (MM) is a hematologic malignancy characterized by proliferation of clonal plasma cells in the bone marrow. The median survival has increased to 6 years in recent years. But MM remains incurable. Some studies about the effects of Chinese herb medicine on MM have been carried out. Long survival in MM patients through Traditional Chinese Medicine (TCM) therapies has been reported rarely before.Patient concernsWe report a case of a female patient who was diagnosed with MM in 2000 at the age of 49. She received 9 cycles of multiple chemotherapeutic regimens mainly based on

Acute Myeloid Leukaemia in Its Niche: the Bone Marrow Microenvironment in Acute Myeloid Leukaemia.

Purpose of reviewAcute myeloid leukaemia (AML) is a heterogeneous malignancy for which treatment options remain suboptimal. It is clear that a greater understanding of the biology of the AML niche will enable new therapeutic strategies to be developed in order to improve treatment outcomes for patients.Recent findingsRecent evidence has highlighted the importance of the bone marrow microenvironment in protecting leukaemia cells, and in particular leukaemic stem cells from chemotherapy-induced cell death. This includes mesenchymal stem cells supporting growth and preventing apoptosis, and alter

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

Preventing and Repairing Myeloma Bone Disease by Combining Conventional Antiresorptive Treatment With a Bone Anabolic Agent in Murine Models.

Multiple myeloma is a plasma cell malignancy, which develops in the bone marrow and frequently leads to severe bone destruction. Current antiresorptive therapies to treat the bone disease do little to repair damaged bone; therefore, new treatment strategies incorporating bone anabolic therapies are urgently required. We hypothesized that combination therapy using the standard of care antiresorptive zoledronic acid (Zol) with a bone anabolic (anti-TGFβ/1D11) would be more effective at treating myeloma-induced bone disease than Zol therapy alone. JJN3 myeloma-bearing mice (n = 8/group) treated w

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

Complete Blood Count Parameters and Bone Health: Clinical and Experimental Evidence.

Osteoporotic fractures pose a significant burden in aging populations, yet current assessment strategies may overlook systemic factors influencing bone health. Emerging evidence suggests that complete blood count (CBC) parameters, including red blood cell indices, white blood cell (WBC) counts and subtypes, and platelet counts, are associated with skeletal fragility and fracture risk. Anemia has been consistently linked to reduced bone mineral density and increased fracture susceptibility, potentially due to impaired oxygen delivery and osteoblast dysfunction. Elevated red cell distribution wi

Update on cutaneous calciphylaxis.

Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently

Induction and Regulation of the Immunoproteasome Subunit β5i (PSMB8) in Laryngeal and Hypopharyngeal Carcinoma Cells.

BACKGROUND The ubiquitin-proteasome pathway (UPP) is closely associated with the occurrence and progression of cancer, and the 5i immunoproteasome subunit is an important antitumor target in UPP. This study aimed to characterize the regulation of the immunoproteasome subunit ß5i (PSMB8) in JHU-011 laryngeal carcinoma cells and FaDu hypopharyngeal carcinoma cells to explore a new target for the treatment of laryngeal and hypopharyngeal carcinomas. MATERIAL AND METHODS JHU-011 and FaDu cells were used as effector cells in this study. By means of ⁶⁰Co γ-irradiation, the construction of stable cel

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

LncRNA NORAD promotes bone marrow stem cell differentiation and proliferation by targeting miR-26a-5p in steroid-induced osteonecrosis of the femoral head.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a devastating orthopedic disease, which seriously affects the quality of life of patients. The study aims to investigate the effects of LncRNA NORAD on SONFH. METHODS: Human bone marrow-derived mesenchymal stem cells (hBMSCs) were isolated from the proximal femur of patients during routine orthopedic surgery and then cultured with dexamethasone (Dex) and transfected with NORAD overexpression vector, siRNA-NORAD and miR-26a-5p mimics. The mRNA expression of NORAD, miR-26a-5p, OPG, RANK, and RANKL was detected by RT-qPCR.

Genes predisposing tunneled catheter thrombosis in hemodialysis patients.

BackgroundThis study aims to investigate the association of genes predisposing thrombophilia with tunneled catheter thrombosis in hemodialysis patients.MethodsBetween October 2018 and December 2020, we compared the frequencies of genetic polymorphisms causing thrombophilia, including prothrombin G20210A, factor V Leiden, methylene tetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, plasminogen activator inhibitor (PAI), factor XIII V34L and clinical characteristics of 52 patients with a history of 2 tunneled2 tunneled catheter thrombosis occlusions within a year (Group 1; 24 males, 28 fema