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ANCA-Associated Glomerulonephritis: Diagnosis and Therapy Proceedings of the Henry Shavelle Lectureship.

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently affects the kidney. Glomerulonephritis (GN) in AAV, ANCA-GN, not only dictates therapeutic decisions but is also of relevance for overall survival influencing the risk of cardiovascular disease and serious infections.SummaryA diagnosis of ANCA-GN includes laboratory investigations including urinalysis and a thorough assessment of potential organ involvement. A kidney biopsy can be performed to ascertain the diagnosis but has an additional prognostic relevance and tools have been established to predict

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… Examples are the co-occurrence of anti-GBM antibodies [ 15 ] or comorbidity by other kidney diseases such as diabetes with kidney disease, multiple myeloma, or tubulo-interstitial nephritis. …

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

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… The first experience with the therapeutic use of anti-IL-6 antibodies dates back to 1988, when mouse anti-IL-6 was tested in patients with multiple myeloma [ 149 ]. … Autocrine Generation and Requirement of BSF-2/IL-6 for Human Multiple Myelomas Nature 1988 332 83 85 10.1038/332083a0 3258060 150. Beck J.T. Hsu S.-M. Wijdenes J. Bataille R. Klein B. Vesole D. Hayden K. Jagannath S. Barlogie B. …

Immunotherapy in Multiple Myeloma.

Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.

The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management.

Antibody deficiency or hypogammaglobulinemia can have primary or secondary etiologies. Primary antibody deficiency (PAD) is the result of intrinsic genetic defects, whereas secondary antibody deficiency may arise as a consequence of underlying conditions or medication use. On a global level, malnutrition, HIV, and malaria are major causes of secondary immunodeficiency. In this review we consider secondary antibody deficiency, for which common causes include hematological malignancies, such as chronic lymphocytic leukemia or multiple myeloma, and their treatment, protein-losing states, and side…

Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology.

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides a comprehensive review of methodologies for evaluating skeletal muscle biomechanics, including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, and single-fiber experiments to assess muscle quality and performance. Furthermore, it elucidates the mechanisms, applications, and limitations of various immunotherapy modalities, including immune checkpoint inhibitors, adoptive ce

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… In untreated smoldering multiple myeloma patients, a high CD8+/Treg ratio is associated with early disease progression ( 56 ). In patients with newly diagnosed multiple myeloma patients undergoing Len/Dex treatment, this ratio was correlated with early relapse ( 57 ). … In ICB-resistant multiple myeloma models, increasing CD8+ T-cell cytotoxicity or depleting Tregs reverses immune therapy resistance and prolongs disease control ( 58 ). …

Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation.

A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironmen

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… Multiple myeloma cells stimulate mesenchymal stromal cells to produce ATX [ 161 ]. In renal cell carcinomas, LPA activates Afr6-regulated mesenchymal pathways via LPA 2 that promote cancer cell plasticity, metastasis and drug resistance [ 162 ]. … A lysophosphatidic acid receptors 1 and 3 axis governs cellular senescence of mesenchymal stromal cells and promotes growth and vascularization of multiple myeloma Stem Cells 2017 35 739 753 10.1002/stem.2499 27641212 162. Hashimoto S. Mikami S. Sugino H. Yoshikawa A. Hashimoto A. Onodera Y. …

Innovations in cancer treatment as novel potential and the myth of personalized vaccines, immunotherapy, CRISPR/Cas9, and bacteriotherapy as promising therapeutic strategies.

Recent advancements in cancer treatment, including targeted therapy, tailored vaccines, immunotherapy, and bacteriotherapy, have demonstrated remarkable potential in addressing various types of cancer. However, the pursuit of novel therapeutic strategies remains challenged by significant obstacles, including toxicity to healthy tissues, limited penetration into malignant tissues, and the potential for tumor cell resistance to pharmacological agents. This study explored the potential of tailored vaccinations, immunotherapy, CRISPR/Cas9, and bacteriotherapy for cancer treatment. Randomized and n

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… Vaccine to Nab-Paclitaxel, Durvalumab and Tremelimumab NCT03606967 | breast carcinoma, | Subcutaneous injection | Evaluate PFS Smoldering Multiple Myeloma NCT06574126 | Multiple myeloma | Subcutaneous injection | Assess the feasibility, intensity and longevity Neo-antigen Vaccine (NeoPepVac) NCT03715985 … Brexucabtagene autoleucel (Tecartus) is licensed for mantle cell lymphoma and B-cell precursor ALL, whereas Idecabtagene vicleucel (Abecma) and Lisocabtagene maraleucel (Breyanzi) were licensed for large B-cell lymphoma and multiple myeloma, respectively [ 65 ]. …

YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?

YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet

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… Prognosis, Treatment Response, and Monitoring Plasma YKL-40 is elevated in some patients with acute myeloid leukemia [ 99 ], multiple myeloma [ 96 , 100 , 101 ], and Hodgkin lymphoma [ 102 ], and high pre-treatment plasma YKL-40 is associated with short survival [ 96 , 99 , 100 ]. … Serum YKL-40 and bone marrow angiogenesis in multiple myeloma Int. J. Cancer 2009 124 1492 1494 10.1002/ijc.24110 19089918 102. Biggar R,J. Johansen J.S. Smedby K.E. Rostgaard K. Chang E.T. Adami H-O. Glimelius B. Molin D. Hamilton-Dutoit S. Melbye M. Hjalgrim H. …

A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.

OBJECTIVES: Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases. METHODS: A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and obse

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… myeloma | San-Miguel et al 75 (2014) phase II | IL-6 | Untreated MM and no candidate for stem cell transplantation | SIL+VMP vs VMP | Complete response rate† Brighton et al 76 (2019) phase II | High-risk smouldering multiple myeloma | SIL vs PBO | 1-year progression-free survival rate Systemic sclerosis … myeloma (MM) did not show improved outcomes such as complete response, progression-free or overall survival in patients with untreated MM ineligible for high dose chemotherapy. 75 SIL further failed to delay the transition from high-risk smouldering multiple myeloma to MM according to the prespecified …

Therapies for Chronic Allograft Rejection.

Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused

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… In the study by Krejcik et al., daratumumab activated and expanded cytotoxic T-cells and decreased CD38-expressing immunosuppressive regulatory T and B cells in patients with multiple myeloma ( Krejcik et al., 2016 ). … Viola et al. demonstrated that daratumumab therapy decreased the count of total NK cells, but it activated CD38-negative NK cells and enhanced expression of CD80/CD86 T-cell costimulatory molecules on monocytes in patients with multiple myeloma. …

Spinal lesions: a comprehensive radiologic overview.

Spinal lesions encompass a diverse range of pathologies, including primary and secondary tumors, infectious processes, vascular malformations, traumatic injuries, and degenerative conditions, each with distinct imaging characteristics crucial for accurate diagnosis and management. Imaging plays vital roles in assessing lesion morphology, anatomical localization, and neurological impact, guiding clinical decision-making and therapeutic planning. This review systematically explores spinal lesions based on their anatomical compartments, highlighting key radiological features and providing a compr

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… Multiple myeloma Multiple myeloma (MM) is the third most common blood cancer in adults. The prevalence of MM is 4.3 cases per 100,000 individuals and is more common in males under the age of 30 with vertebral involvement in 65% of cases ( 131 ). … Figure 24 Multiple myeloma. Sagittal T1 (A) , sagittal T2 (B) , sagittal T1 + C (C) , and sagittal STIR (D) MRI of the lumbar spine demonstrating diffuse T1 hypointense, heterogenous T2 hyperintense, and T1 + C enhancing lesions representing vertebral manifestations of multiple myeloma. …

Rapid Progress in Immunotherapies for Multiple Myeloma: An Updated Comprehensive Review.

Despite rapid advances in treatment approaches of multiple myeloma (MM) over the last two decades via proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), their efficacies are limited. MM still remains incurable, and the majority of patients shortly relapse and eventually become refractory to existing therapies due to the genetic heterogeneity and clonal evolution. Therefore, the development of novel therapeutic strategies with different mechanisms of action represents an unmet need to achieve a deep and highly durable response as well as to improve pa…

Cardiac Cachexia: Unaddressed Aspect in Cancer Patients.

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are au

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… However, certain types of cancers are more prone to develop heart failure, such as multiple myeloma (14.4%), leukemia (10.4%), lymphoma (9.7%), and lung cancer (8.5%). …

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achi

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… As evidenced in related studies, patients with HDM, above all those with acute lymphoblastic leukemia (ALL), essential thrombocytopenia (ET), multiple myeloma (MM), and chronic myeloid leukemia (CML), compared to people without such conditions, have experienced a higher chance of infection with COVID … Multiple myeloma Another type of HDM is multiple myeloma (MM), which affects plasma cells in the bone marrow [ 192 ]. In cases with MM, the immune system is often compromised by various factors making people with this malignancy susceptible to infection [ 193 ]. …

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

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… Clinical development is underway for breast cancer, multiple myeloma, T-cell leukemia, and T-cell lymphoma in several countries. … Clinical development is underway for breast cancer, multiple myeloma, T-cell leukemia, and T-cell lymphoma in several countries. …

Piperine: From Green Extraction to Clinical Translation-A Review.

BACKGROUND: Piperine has diverse pharmacological and bioenhancing activities, but poor aqueous solubility, variable exposure, interaction liability, and discontinuity across production, formulation, and clinical evaluation limit translation. This review integrates these frequently separated stages. METHODS: A structured narrative PubMed search covered English-language studies published from 1 January 2021 to 27 April 2026, supplemented by ClinicalTrials.gov records checked through 13 June 2026, backward citation searching, and selected earlier seminal studies. Evidence was synthesized by expe

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment.

Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers cur

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… SAE 2/3 (66.67%) at dose level 2 | Leukemia, Myeloid, Acute | Drug: G-CSF|Drug: Plerixafor|Drug: Mitoxantrone|Drug: Etoposide|Drug: Cytarabine | Phase 1|Phase 2 | 39 13 | NCT00903968 | Combination Plerixafor (AMD3100)and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma | Completed | SD … This drug was initially developed for treatment and prevention of HIV, but has now also been approved for treatment of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) ( 167 , 168 ). …

Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?

Despite significant progress in cancer prevention, screening, and treatment, the still limited number of therapeutic options is an obstacle towards increasing the cancer cure rate. In recent years, many efforts were put forth to develop therapeutics that selectively target different components of the oncogenic Wnt/β-catenin signaling pathway. These include small molecule inhibitors, antibodies, and more recently, gene-based approaches. Although some of them showed promising outcomes in clinical trials, the Wnt/β-catenin pathway is still not targeted in routine clinical practice for cancer mana

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… In a phase II clinical trial evaluating disease response in patients with smoldering multiple myeloma ( NCT01302886 ), intravenous administration of BHQ880 was well tolerated and associated with stable disease in most patients. … Anti-DKK1 mAb (BHQ880) as a Potential Therapeutic Agent for Multiple Myeloma Blood 2009 114 371 379 10.1182/blood-2008-11-191577 19417213 PMC2714212 112. Iyer S.P. Beck J.T. Stewart A.K. Shah J. Kelly K.R. Isaacs R. Bilic S. Sen S. Munshi N.C. …

Exosomes: innovative biomarkers leading the charge in non-invasive cancer diagnostics.

Exosomes, nanoscale extracellular vesicles secreted by diverse cell types, have emerged as promising biomarkers for non-invasive tumor diagnostics, offering significant advantages over traditional methods. These vesicles, typically ranging from 30 to 150 nanometers in size, carry a diverse cargo of proteins, lipids, RNA, and microRNAs, which reflect the molecular alterations occurring within their parent cells. Notably, exosomes can be isolated from easily accessible biofluids such as blood, urine, and saliva, making them ideal candidates for liquid biopsy applications. This review explores th

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… Multiple myeloma (MM) is a malignancy of plasma cell disorder characterized by the clonal proliferation of abnormal plasma cells in the bone marrow. …

Antibodies to watch in 2021.

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed an

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… , EU/US Orphan Tafasitamab | MONJUVI | CD19; Humanized IgG1 | Diffuse large B-cell lymphoma | In review | 31–07-2020 | BT, FT, EU/US Orphan Belantamab mafodotin | BLENREP | BCMA; Humanized IgG1 ADC | Multiple myeloma | 25–08-2020 | 05–08-2020 | BT, PRIME, EU/US Orphan Satralizumab | ENSPRYNG | IL-6 R … Isatuximab (Sanofi) Isatuximab (Sarclisa®, isatuximab-irfc) is a chimeric IgG1k that targets CD38 overexpressed on plasma cells in multiple myeloma (MM). Ixatuximab was granted Orphan Drug designations by the European Medicines Agency (EMA) and the FDA in 2014 and 2016, respectively. …