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Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

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… Hemophilia A and B are prime examples of hematologic disorders caused by a deficiency in secreted acellular blood components. 283 The estimated prevalence for hemophilia A and B are ~12:100,000 and 4:100,000, respectively. 284 Hemophilia A and B are caused by factor VIII (FVIII) and factor XI (FXI) deficiency …

The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids.

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia

Balancing Innovation and Access: Insights from AIM's Fair Pricing Model and Its Current and Future Applications.

OBJECTIVE: Access to affordable medicines is a cornerstone of equitable healthcare, yet escalating drug prices increasingly strain national healthcare systems. Cost-based pricing can be a useful complement to value-based pricing, provided that relevant variables are considered. METHODS: We applied the International Association of Mutual Benefit Societies (AIM) Fair Pricing Model to ten market-protected medicines authorized by the European Medicines Agency between 2015 and 2018, covering oncology, rare diseases, and chronic conditions. Analyses were conducted across six European countries-Belg

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… Three medicines were for the treatment of a (ultra) rare disease: emicizumab (Hemlibra®) for preventing bleeding in patients with hemophilia A with factor VIII inhibitors (first indication) or without factor VIII inhibitors (second indication), selexipag (Uptravi®) for pulmonary hypertension, and mepolizumab … For Ocrevus ® and Hemlibra ® the fair price was taken into account for the second indications (RMS for Ocrevus ® and preventing bleeding in patients with hemophilia A without factor VIII inhibitors for Hemlibra ® ) to calculate the difference between fair price and real costs FP fair prices, AC actual …

Adding recombinant AAVs to the cancer therapeutics mix.

Gene therapy is a powerful biological tool that is reshaping therapeutic landscapes for several diseases. Researchers are using both non-viral and viral-based gene therapy methods with success in the lab and the clinic. In the cancer biology field, gene therapies are expanding treatment options and the possibility of favorable outcomes for patients. While cellular immunotherapies and oncolytic virotherapies have paved the way in cancer treatments based on genetic engineering, recombinant adeno-associated virus (rAAV), a viral-based module, is also emerging as a potential cancer therapeutic thr

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… Efficient production of dual recombinant adeno-associated viral vectors for factor VIII delivery. Hum. Gene Ther. Methods. 2014;25:261–268. doi: 10.1089/hgtb.2014.093. 169. … Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A. Haematologica. 2015;100:881–892. doi: 10.3324/haematol.2014.123117. 170. …

Cancer-Associated Thrombosis: A New Light on an Old Story.

Cancer-associated thrombosis (CAT) is a rising and significant phenomenon, becoming the second leading cause of death in cancer patients. Pathophysiology of CAT differs from thrombosis in the non-cancer population. There are additional risk factors for thrombosis specific to cancer including cancer type, histology, and treatment, such as chemotherapy. Recently developed scoring systems use these risk factors to stratify the degree of risk and encourage thromboprophylaxis in intermediate- to high-risk patients. Anticoagulation is safely used for prophylaxis and treatment of CAT. Both of these h

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… However, this may be due to higher levels of factor VIII, von Willebrand factor and D-dimer along with increased thrombophilias (especially sickle cell disease) in this patient population [ 40 ]. … Radiotherapy has been found to cause a pro-coagulant response and haemostasis through increasing D-dimer, activated factor VIII, TF and von Willebrand factor, the latter of which can also cause endothelial dysfunction and thrombosis [ 63 , 64 ]. 3.4. …

Gene therapy: principles, challenges and use in clinical practice.

INTRODUCTION: Gene therapy is an emerging topic in medicine. The first products have already been licensed in the European Union for the treatment of immune deficiency, spinal muscular atrophy, hemophilia, retinal dystrophy, a rare neurotransmitter disorder and some hematological cancers, while many more are being assessed in preclinical and clinical trials. OBJECTIVE: The purpose of this review is to provide an overview of the core principles of gene therapy along with information on challenges and risks. Benefits, adverse effects and potential risks are illustrated based on the examples of

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… Hemophilia a and b Hemophilia, an X‑linked recessive bleeding disorder, is caused by a deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B) due to mutations in the genes encoding for these factors. … Bioengineering of coagulation factor VIII for improved secretion. Blood. 2004;103(9):3412–9. 10.1182/blood-2003-10-3591. 89. Soucie JM, Monahan PE, Kulkarni R, Konkle BA, Mazepa MA; US Hemophilia Treatment Center Network. …

Oral Communication abstracts

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Prevention of venous thromboembolism in ambulatory patients with cancer.

Patients with cancer are at high risk of venous thromboembolic events, and this risk can be further increased in patients with certain cancer types and by cancer treatments. Guidelines on the prevention of cancer-associated thrombosis (CAT) recommend thromboprophylaxis for hospitalised patients; however, this is not routinely recommended for ambulatory patients receiving chemotherapy and is limited to specified high-risk patients. Identification of the ambulatory patients at risk of CAT who would most benefit from anticoagulant therapy is therefore critical to reduce the incidence of this comp

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… CCL3, chemokine (C-C motif) ligand 3; CRP, C reactive protein; FVIII, factor VIII; NET, neutrophil extracellular trap; sVEGF, soluble vascular endothelial growth factor; TF-MP, tissue factor bearing microparticles; VTE, venous thromboembolism. … High factor VIII levels independently predict venous thromboembolism in cancer patients: the Cancer and Thrombosis Study. Arterioscler Thromb Vasc Biol 2009;29:2176–81. 10.1161/ATVBAHA.109.190827 39. Watson HG, Keeling DM, Laffan M, et al. Guideline on aspects of cancer-related venous thrombosis. …

Contemporary Challenges in Venous Thromboembolism: Evolving Populations and Implications for Management and Risk Stratification.

Venous thromboembolism (VTE) remains a major cause of morbidity and mortality globally. The incidence of VTE continues to increase over time, contributed to by demographic shifts and emerging risk factors, such as novel cancer treatments and exposure to gender-affirming hormonal therapies. While the introduction of direct oral anticoagulants (DOACs) revolutionized VTE management, increasing complexity in select patient cohorts has driven the need for alternative treatment strategies, including pharmacological and interventional approaches. Concurrently, contemporary patient populations have ex

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… Notably, elevated factor VIII (FVIII) has been associated with VTE risk. The landmark Leiden Thrombophilia Study demonstrated FVIII activity levels > 150 IU/dL were associated with an approximately 5-fold increase in VTE (OR 4.8, 95% CI 2.3–10.0) [ 126 ]. … Association between elevated plasma levels of factor VIII and risk of recurrent venous thromboembolism: A systematic review and meta-analysis J. Thromb. Thrombolysis 2025 59 95 109 10.1007/s11239-025-03161-8 40745407 128. Bosch A. Uleryk E. Avila L. …

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools.

Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or

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… Association studies so far have hypothesized a role for increased vonWillenbrand factor (VWF), factor VIII, and tissue factor (TF), which mediate procoagulant effects on endothelial cells. … Extremely high levels of von Willebrand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. J. Thromb. …

Приобретенный изолированный фактор VII Недостаток в ячейке Плазмы: краткое представление Two Дела, связанные с Плазмой-Келл-Леукемией, и обзор литературы.

Приобретенный изолированный фактор VII (FVII) недостаток является редким, но важным открытием у пациентов с расстройствами плазменных клеток, имеющими значительные терапевтические и прогнозные последствия. Цель настоящего анализа и обзора случаев, о которых сообщается в литературе, состоит в том, чтобы высветить связанные с болезнями характеристики, связанные с этим редким свертываемым дефектом, клиническими проявлениями и результатами, а также потенциальными основополагающими механизмами и дать руководящие указания в отношении методов лечения этих пациентов с точки зрения профилактических и т

Calvarial Metastasis as the Initial Presentation in Hepatocellular Carcinoma: A Rare Entity.

Hepatocellular carcinoma (HCC) presenting as calvarial metastasis (CM) is a rare situation with limited reports in literature. We present a case of a 64-year-old gentleman, who presented with an 8-month history of swelling on the right forehead, associated with decreased vision and size of the right eye. Magnetic resonance imaging revealed a partially hemorrhagic lesion in the right frontal bone, extending into the scalp and causing a midline shift, with intra-orbital and intraconal extension. Positron emission tomography showed multiple bi-lobar liver metastases. The patient was diagnosed wit

P1574: EFFICACY AND SAFETY OF TIXAGEVIMAB AND CILGAVIMAB (EVUSHELD) IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

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… Patients with hemophilia А received a prophylactic dose of factor VIII before the administration of Evusheld. Results: Median follow up was 6 months (range 4-9). In group of patients who received prophylactic dose no obvious side effects were observed after administration of the moAb. …

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

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… Also, endothelial cells can produce factor VIII and express TF upon activation, while also generating FV, FX, and prothrombin (FII) for surface-bound thrombin generation. …

Occult cirrhosis presenting as progressive tremor: acquired hepatocerebral degeneration induced by traditional Chinese medicine and natural health products, aggravated by manganese supplements: A case report.

RATIONALE: Acquired hepatocerebral degeneration (AHD) is a rare neurological complication of chronic liver disease or portosystemic shunting, typically characterized by extrapyramidal symptoms and manganese accumulation in the basal ganglia. Its diagnosis is particularly challenging in patients with occult cirrhosis and complex exposure histories, especially when traditional Chinese medicines (TCM) and natural health products (NHPs) contribute to hepatotoxicity. PATIENT CONCERNS: A 66-year-old woman presented with a 2-year history of progressive postural and intention tremor, with marked wors

Combination with third-generation bisphosphonate (YM529) and interferon-alpha can inhibit the progression of established bone renal cell carcinoma.

The aim of this study was to investigate whether the third-generation nitrogen-containing bisphosphonate (YM529) can inhibit the progression of established bone renal cell carcinoma (RCC) and to elucidate its mechanism. Antiproliferative effect and apoptosis induction of RCC cells and mouse osteoclasts by YM529 and/or interferon-alpha (IFN-α) were evaluated in vitro using cell counting and in vivo using soft X-ray, the TUNEL method and tartrate-resistant acid phosphatase stain. For the in vivo study, male athymic BALB/cA Jc1-nu nude mice bearing human RCC cell line RBM1-IT4 cells were treated

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… We used an antihuman factor VIII protein polyclonal antibody (dilution 1:200; DAKO, Kyoto, Japan). … Micro-vessel density quantification Micro-vessel density (MVD) was determined by microscopy immediately after immunostaining of the section with anti-Factor VIII antibody according to the procedure used in a previous study. …

Comparison of 24-hour versus random urine samples for determination and quantification of Bence Jones protein in a South African population.

BackgroundThe International Myeloma Working Group and College of American Pathologists recommend a 24-h urine collection to determine the Bence Jones protein (BJP) excretion level for monitoring treatment response in patients with multiple myeloma (MM). There are several issues related to sample collection and the method is prone to inaccuracy.ObjectiveThis study compared measured 24-h to random urine collections for the quantitation of BJP in a South African population.MethodsSixty-six patients with MM submitted random urine samples with their routine 24-h urine collection from April 2016 - M

A narrative review of the epidemiological and mechanistic associations between ABO blood groups and diseases: focusing on cardiovascular diseases, cancers, diabetes, malaria, COVID-19 and rheumatic diseases.

BACKGROUND: The ABO blood group system is one of the most clinically significant human blood group systems and is closely associated with pathogenesis, progression, and prognosis of numerous diseases. This narrative review synthesizes recent epidemiological evidence and explores potential mechanisms linking ABO to cardiovascular diseases, malignancies, diabetes, Plasmodium falciparum malaria, COVID‑19, and rheumatic diseases. METHODS: We searched PubMed and CNKI up to September 2025. RESULTS: Epidemiological studies consistently show non‑O blood groups have significantly elevated cardiovascu

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… One well-characterized mechanism involves ABO genetic variants regulating glycosyltransferase activity, which subsequently modulates plasma levels of von Willebrand factor (VWF) and factor VIII, as well as the expression of endothelial cell adhesion molecules. … Non-O individuals exhibit 25%– 30 % higher VWF and factor VIII concentrations than type O individuals [ 67–70 ]. …

The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor.

BackgroundMultiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefor

Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria. Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high-output heart failure. Families with the same mutatio

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… The low serum iron levels in HHT patients have been associated with elevated factor VIII levels, along with a 2.5-fold increased risk of VTE events. 67 In those patients who develop a VTE, therapeutic anticoagulation can be administered. … Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia. Thorax. 2012;67(4):328–333. 68. Peng HL, Yi YF, Zhou SK, Xie SS, Zhang GS. …