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Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su

ISEV2021 Abstract Book

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Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen rece

Nanomedicine Meets Immunotherapy: Advancing Adoptive Cell Therapy with Nanoparticles in the Treatment of Cancer with Sustainability Perspectives.

Immunotherapy has achieved remarkable clinical success in certain cancers, particularly through adoptive cell therapy (ACT), where T cell engineering with chimeric antigen receptor (CAR) has driven major clinical breakthroughs in the treatment of hematologic malignancies. However, efficacy against solid tumors remains limited due to multiple barriers, including the scarcity of tumor-specific antigens, antigen heterogeneity, immunosuppressive tumor microenvironment, and physical obstruction of T cell infiltration by dense extracellular matrix. Nanoparticle (NP)-based approaches can overcome the

Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.

Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the paradigm in hematological malignancies. However, its efficacy in treating solid tumors remains limited because the immunosuppressive tumor microenvironment (ITME) seriously blocks T cell activation, infiltration, and proliferation. Cytokines, driving potent assisted function by enhanced T cell expansion, persistence, and direct tumor cell killing, have long been acknowledged as promising candidates combined with CAR-T cells to improve treatment outcomes. Despite their preclinical success, significant toxicity occurs in

Delivery of miR-34a by chitosan/PLGA nanoplexes for the anticancer treatment of multiple myeloma.

The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant

Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group.

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (E

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… Non-hematologic toxicity was usually mild, the most common AE being fatigue (39 %), gastrointestinal (38 %), unspecified pain (30 %), and injection site reactions (22 %). Infectious complications of any grade were documented in 63 %, febrile neutropenia in 19 % (Table 3 ). … site reaction | G1-2 | 64 (21.2) | 123 G3-4 | 2 (0.7) | 2 Fatigue | Relieved by rest | 46 (15.2) | 89 Not relieved by rest | 36 (11.9) | 63 Limiting self care | 37 (12.3) | 42 Pain | Mild | 43 (14.2) | 82 Moderate | 39 (12.9) | 51 Severe | 9 (3.0) | 9 Surgery | Elective | 19 (6.3) | 23 Emergency | 10 …

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications.

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-r

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.

Pharmaceutical companies keep producing novel drugs and drug treatments for improving the life of every sick individual, most often following a pattern; a specific drug for a specific condition. Evidence suggests that different medications can have a positive effect on different pathological conditions. The full potential of existing therapies can be revealed through drug repurposing-also referred to as drug repositioning, reprofiling, or re-tasking-which involves identifying new therapeutic uses for approved or investigational drugs beyond their original indications. One significant target in

Non-Curcuminoids from Turmeric and Their Potential in Cancer Therapy and Anticancer Drug Delivery Formulations.

Over the past decades curcuminoids have been extensively studied for their biological activities such as antiulcer, antifibrotic, antiviral, antibacterial, antiprotozoal, antimutagenic, antifertility, antidiabetic, anticoagulant, antivenom, antioxidant, antihypotensive, antihypocholesteremic, and anticancer activities. With the perception of limited toxicity and cost, these compounds forms an integral part of cancer research and is well established as a potential anticancer agent. However, only few studies have focused on the other bioactive molecules of turmeric, known as non-curcuminoids, wh

Emerging agents and regimens for multiple myeloma.

The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for R

Review of Potential Barriers to Effective Hemostatic Management of Acquired Hemophilia A by Non-Hemophilia Experts in the United States.

Acquired hemophilia A (AHA) is an ultra-rare autoimmune disorder caused by autoantibodies against factor VIII. It often presents with life-threatening bleeding to non-hemophilia experts, who have limited awareness of this condition. This review evaluated hemostatic management and identified barriers to optimal management of AHA by non-hemophilia experts in the United States through a literature review. AHA case reports published by non-hemophilia experts from January 2016 through November 2021 in non-hematology journals were critically reviewed for a chronology of clinical course and managemen

Time to evolve: predicting engineered T cell-associated toxicity with next-generation models.

Despite promising clinical results in a small subset of malignancies, therapies based on engineered chimeric antigen receptor and T-cell receptor T cells are associated with serious adverse events, including cytokine release syndrome and neurotoxicity. These toxicities are sometimes so severe that they significantly hinder the implementation of this therapeutic strategy. For a long time, existing preclinical models failed to predict severe toxicities seen in human clinical trials after engineered T-cell infusion. However, in recent years, there has been a concerted effort to develop models, in

Увязка патогенеза с падением риска при множественном склерозе.

Множественный склероз — это хроническое неврологическое расстройство, характеризующееся постепенной инвалидностью, при этом падение является значительным следствием его физических и когнитивных расстройств. В настоящем обзоре рассматриваются основные вкладчики, с тем чтобы снизить риск для лиц с множественным склерозом, и анализируются более широкие последствия этих факторов, такие, как боязнь падения. К основным факторам, связанным с падением риска, относятся аномалии, когнитивная дисфункция и усталость. Эти факторы часто взаимодействуют друг с другом, что приводит к ограничению мобильности и

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… It also can cause side effects, including flu-like symptoms and injection site reactions [ 106 ]. Early initiation of DMTs before an MS diagnosis has been shown to lower the risk of a first clinical episode, emphasizing the importance of timely diagnosis and intervention [ 107 ]. …

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Chronic pruritus: a narrative review.

Chronic pruritus encompasses a manifestation of several cutaneous, allergic, infectious, neurological, psychological, and systemic conditions, whose etiological investigation and therapeutic strategy can be challenging. This comprehensive review aims to enhance the understanding of pruritus by highlighting important elements in its pathogenesis, including keratinocytes, Merkel cells and mast cells, nerve fibers, histaminergic and nonhistaminergic pathways, and the interaction of itch signals with the central nervous system. Diagnostic evaluation of chronic pruritus may require a meticulous app

Guidelines for the management of osteoporosis and fragility fractures.

The purpose of this document, a result of the harmonisation and revision of Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT associations, is to provide practical indications based on specific levels of evidence and various grades of recommendations, drawn from available literature, for the management of osteoporosis and for the diagnosis, prevention, and treatment of fragility fractures. These indications were discussed and formally approved by the delegates of the Italian Scientific Associations involved in the project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIO

Абстрактный сборник ISEV2022.

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Spinal metastasis: narrative reviews of the current evidence and treatment modalities.

The treatment for spinal metastasis has evolved significantly during the past decade. An advancement in systemic therapy has led to a prolonged overall survival in cancer patients, thus increasing the incidence of spinal metastasis. In addition, with the improved treatment armamentarium, the prediction of patient survival using traditional prognostic models may have limitations and these require the incorporation of some novel parameters to improve their prognostic accuracy. The development of minimally-invasive spinal procedures and minimal access surgical techniques have facilitated a quicke