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Research progress in inducing immunogenic cell death of tumor cells.

Immunogenic cell death (ICD) is a regulated cell death (RCD) pathway. In response to physical and chemical signals, tumor cells activate specific signaling pathways that stimulate stress responses in the endoplasmic reticulum (ER) and expose damage-associated molecular patterns (DAMPs), which promote antitumor immune responses. As a result, the tumor microenvironment is altered, and many tumor cells are killed. The ICD response in tumor cells requires inducers. These inducers can be from different sources and contribute to the development of the ICD either indirectly or directly. The combinati

Shilajit mitigates chemotherapeutic drug-induced testicular toxicity: Study on testicular germ cell dynamics, steroidogenesis modulation, and Nrf-2/Keap-1 signaling.

BACKGROUND: Medications, including chemotherapeutic drugs, contribute to male infertility as external factors by inducing oxidative stress in testicular cells. Shilajit is a naturally occurring bioactive antioxidant used in Ayurvedic medicine to treat a variety of ailments. OBJECTIVE: This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics. MATERIAL AND METHODS: Male Parkes mice received single intraperitoneal CPA injection (200 mg/kg BW) on day one, followed by daily supplementation

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… Cyclophosphamide induced oxidative stress, lipid per oxidation, apoptosis and histopathological changes in rats: protective role of boron J Trace Elem Med Biol 62 2020 126574 10.1016/j.jtemb.2020.126574 32516632 23 Pant K Gupta P Damania P Yadav AK Gupta A Ashraf A. …

Multiple myeloma: the (r)evolution of current therapy and a glance into future.

Over the past 20 years, the regulatory approval of several novel agents to treat multiple myeloma (MM) has prolonged median patient survival from 3 to 8-10 years. Increased understanding of MM biology has translated to advances in diagnosis, prognosis, and response assessment, as well as informed the development of targeted and immune agents. Here we provide an overview of the recent progress in MM, and highlight research areas of greatest promise to further improve patient outcome in the future.

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… The irreversible covalent epoxyketone PI carfilzomib, either alone or in combination with lenalidomide, has been approved to treat RRMM. 39 Ixazomib, the first oral boronic acid-based PI, has been approved, alone and in combination with lenalidomide, to treat RRMM; 40 this all-oral regimen showed low …

Feasibility of Long-term Proteasome Inhibition in Multiple Myeloma by in-class Transition From Bortezomib to Ixazomib.

BACKGROUND: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral IRd (ixazomib-lenalidomide-dexamethasone) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence and duration while maintaining patients' health-related quality of life (HRQoL) and improving outcomes. PATIENTS AND METHODS: US community sites are enrolling non-transplant-eligible patients with newly diagnosed multiple myeloma (MM) with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive IRd (up to 39

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… The i CT is made possible by the availability of ixazomib, an oral, once-weekly, boron-based, reversible PI, 16 which has been approved for use in combination with Rd (lenalidomide, dexamethasone) for treatment of patients with MM who have received ≥ 1 prior therapy. 17 The feasibility of long-term ixazomib-Rd …

Evolving Paradigms in the Management of Multiple Myeloma: Novel Agents and Targeted Therapies.

Multiple myeloma (MM) is a clonal plasma cell disorder defined by bone marrow infiltration and osteolytic bone lesions and is the second most common hematologic malignancy after non-Hodgkin lymphoma. The landscape of MM treatment was transformed at the dawn of the twenty-first century by the introduction of novel agents including proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide), which have prolonged the survival of MM patients. The recently revised International Myeloma Working Group diagnostic criteria for MM added validated biomarkers (clonal bone mar

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… Bortezomib is a dipeptide boronic acid and reversible inhibitor of the 20S proteasome primarily at the chymotrypsin-like and caspase-like active sites [ 67 ]. …

Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma.

Lung diseases, including COVID-19 and lung cancers, is a huge threat to human health. However, for the treatment and diagnosis of various lung diseases, such as pneumonia, asthma, cancer, and pulmonary tuberculosis, are becoming increasingly challenging. Currently, several types of treatments and/or diagnostic methods are used to treat lung diseases; however, the occurrence of adverse reactions to chemotherapy, drug-resistant bacteria, side effects that can be significantly toxic, and poor drug delivery necessitates the development of more promising treatments. Nanotechnology, as an emerging t

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… Design of boronic acid-attributed carbon dots on inhibits HIV-1 entry. RSC Adv. 2016;6:92996–93002. doi: 10.1039/C6RA21062G. [199] Łoczechin A, Séron K, Barras A, Giovanelli E, Belouzard S, Chen Y T, Metzler-Nolte N, Boukherroub R, Dubuisson J, Szunerits S. …

Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in the

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… Introduction Bortezomib (BTZ), a dipeptidyl boronic acid, is an anticancer drug mostly used in the treatment of multiple myeloma [ 1 – 4 ] and also in solid tumor treatment [ 5 – 7 ]. …

Cancer Therapy-Induced Encephalitis.

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy-particularly immune checkpoint inhibitors-has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as im

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… Widemann B.C., Balis F.M., Shalabi A., Boron M., O’Brien M., Cole D.E., Jayaprakash N., Ivy P., Castle V., Muraszko K., et al. Treatment of Accidental Intrathecal Methotrexate Overdose With Intrathecal Carboxypeptidase G2. JNCI J. Natl. Cancer Inst. 2004;96:1557–1559. doi: 10.1093/jnci/djh270. 82. …

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.

Protein quality control allows eukaryotes to maintain proteostasis under the stress of constantly changing conditions. In this review, we discuss the current literature on PQC, highlighting flaws that must exist for malignancy to occur. At the nidus of PQC, the expression of BAG1-6 reflects the cell environment; each isoform directs proteins toward different, parallel branches of the quality control cascade. The sum of these branches creates a net shift toward either homeostasis or apoptosis. With an established role in ALP, Bag3 is necessary for cell survival in stress conditions including th

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… Boronates, bortezumib, and ixazomib reversibly obstruct the 20S core, while epoxyketones, carfilzomib, and oprozomib irreversibly bind and disable the active site. …

Molecular Delivery of Cytotoxic Agents via Integrin Activation.

Integrins are cell adhesion receptors overexpressed in tumor cells. A direct inhibition of integrins was investigated, but the best inhibitors performed poorly in clinical trials. A gained attention towards these receptors arouse because they could be target for a selective transport of cytotoxic agents. Several active-targeting systems have been developed to use integrins as a selective cell entrance for some antitumor agents. The aim of this review paper is to report on the most recent results on covalent conjugates between integrin ligands and antitumor drugs. Cytotoxic drugs thus conjugate

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… An oxidized dextran (Dex- CHO) was functionalized by Schiff base and boronic esterification reactions with cyclo-(Arg-Gly-Asp-D-Phe-Lys) (c(RGDfK)), doxorubicin, and bortezomib. …

Emerging Strategies Targeting Catabolic Muscle Stress Relief.

Skeletal muscle wasting represents a common trait in many conditions, including aging, cancer, heart failure, immobilization, and critical illness. Loss of muscle mass leads to impaired functional mobility and severely impedes the quality of life. At present, exercise training remains the only proven treatment for muscle atrophy, yet many patients are too ill, frail, bedridden, or neurologically impaired to perform physical exertion. The development of novel therapeutic strategies that can be applied to an in vivo context and attenuate secondary myopathies represents an unmet medical need. Thi

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… Bortezomib (otherwise termed Velcade TM or PS-341) is a selective boronic acid proteasome inhibitor approved by the United States Food and Drug Administration and used as a third-line treatment of multiple myeloma and mantle cell lymphoma [ 73 ]. …

Cancer treatment using peptides: current therapies and future prospects.

This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or

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… The drug is an N-protected dipeptide and can be written as Pyz-Phe-boroLeu, which stands for pyrazinoic acid, phenylalanine, and leucine with a boronic acid instead of a carboxylic acid. Mifamurtide (Mepact) is a drug against osteosarcoma, which is lethal in about a third of cases [ 147 ]. …

Ферроптоз в множестве миеломы: молекулярные механизмы и терапевтические возможности.

Множественная миелома (ММ) — гематологическая порча, вызванная распространением клональных плазменных клеток, и остается в значительной степени неизлечимой из-за рецидива заболеваний и приобретенной лекарственной устойчивости. Ферроптоз, основанная на железной зависимости форма регулируемой клеточной смертности, характеризующейся чрезмерным липидным пероксидацией, стала потенциальной терапевтической целью в раке и все чаще причастна к биологии MM. В отличие от апоптоза и других классических путей смерти клеток, ферроптоз тесно связан с дисрегулируемым метаболизмом железа, окислительным стрессо

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… Preclinical studies suggest that ascorbic acid may antagonize the antitumor activity of bortezomib in vivo , potentially through direct interactions with boronic-acid-containing proteasome inhibitors. …

Targeted Hybrid Nanocarriers as Co-Delivery Systems for Enhanced Cancer Therapy.

Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects i

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… Combining magnetic nanoparticles and icosahedral boron clusters in biocompatible inorganic nanohybrids for cancer therapy. Nanomedicine. 2019;20:101986. doi: 10.1016/j.nano.2019.03.008. 80. Hameed S, Bhattarai P, Dai Z. …

Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells.

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In thi

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… Boron neutron capture therapy: Moving toward targeted cancer therapy. J Cancer Res Ther. 2016;12(2):520‐525. 3. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941‐1953. 4. Sun Y. …

Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma.

Carfilzomib, a selective proteasome inhibitor (PI), is approved for the treatment of patients with relapsed or refractory multiple myeloma (MM). Combination regimens incorporating a PI and immunomodulatory drug (IMiD) have been associated with deep responses and extended survival in patients with newly diagnosed MM (NDMM). Carfilzomib-based combinations with immunomodulators are being extensively studied in the frontline setting. The objective of this review was to describe efficacy and safety data for carfilzomib-based, PI/immunomodulatory combinations in NDMM. Information sources were articl

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… Carfilzomib has a structure (tetrapeptide epoxyketone) differentiated from the first-generation PI bortezomib (dipeptide boronate) [ 8 ]. …

Интеграция нанотехнологий в онкологию для передовых стратегий наночастиц в целевую диагностику и лечение рака.

Рак остается одной из основных глобальных проблем в области здравоохранения. Обычная терапия часто ограничивается низкой избирательностью опухолей, системной токсичностью, резистентностью к многочисленным лекарствам и неоптимальными фармакокинетиками. Нанотехнология предлагает преобразующий подход в онкологии. Она позволяет осуществлять целенаправленные поставки наркотиков, контролировать или стимулировать их высвобождение и использовать многофункциональные платформы, сочетающие в себе терапию и диагностику. Нанопчасти повышают растворимость наркотиков, продлевают циркуляцию и повышают внутрик

Clinically proven natural products against breast cancer, with mechanistic insights.

BackgroundBreast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14% of all female cancer-related deaths worldwide. This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.MethodologyRequired data for this review article was retrieved employing several readily obtainable search databases, including Web of Science® (Thomson Reuters, USA), PubMed® (U.S. National Library of Medicine, USA), and SciVerse Scopus® (Elsevier Properties S.A., USA), takin

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… Impact of inadequate concentration of boron in seed storage proteins content in oilseed crops. In: Grain and seed proteins functionality. London: IntechOpen; 2021. doi: 10.5772/intechopen.95873. 135. Shahada C, Morya S, Awuchi CG. …

Компьютерный подход к разработке лекарственных средств для множественного склероза с помощью модели QSPR, теории химических графиков и анализа решений по нескольким критериям.

Множественный склероз (MS) — сложное аутоиммунное заболевание центральной нервной системы с неизвестной этиологией. Несмотря на то, что медикаментозная терапия может замедлить прогресс, существует необходимость в более эффективном лечении. Модель количественного соотношения структуры и активности (QSAR) с использованием топографических индексов, полученных на основе теории химических графиков, является многообещающим подходом к рациональному проектированию новых лекарств для MS. Используя подход линейной регрессии, мы создаём модели количественного соотношения структуры и производительности (Q

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… Correlation between the Estrada index and π-electronic energies for benzenoid hydrocarbons with applications to boron nanotubes. Int J Quantum Chem, 119(23), e26016. 20. Parveen S, Farooq FB, Awan NUH, Fanja R, Choudhary MF. (2022). …

Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.

BackgroundLoss of P-glycoprotein (P-gp) at the blood-brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer's disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin-proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor

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… BTZ is a boronic acid dipeptide derivative with C max of 106.2 ± 46.7 ngh/ml and a half-life (t ½ ) of 78.9 ± 50.9 h [ 65 ]. Treatment is by intravenous injection, with recommendation to not use any other route. …