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Carfilzomib: a novel treatment in relapsed and refractory multiple myeloma.

Carfilzomib is a second-generation proteasome inhibitor with well-documented clinical activity as a single agent in patients with relapsed/refractory multiple myeloma. Carfilzomib can partially overcome resistance in bortezomib-refractory patients and has significant efficacy in bortezomib-naïve patients. Responses generally occur rapidly and are durable in the majority of cases. Carfilzomib can be safely administered in patients with renal failure and adverse cytogenetics do not seem to interfere with its activity. Moreover, carfilzomib has the advantage of a favorable safety profile, especia

Anticancer natural products from the Middle East and North Africa: biodiversity, mechanisms, and translational challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, imposing substantial clinical, societal, and economic burdens. Despite major advances in surgical oncology, systemic chemotherapy, radiation therapy, molecularly targeted therapeutics, and immune checkpoint inhibition, contemporary cancer treatment remains constrained by dose-limiting toxicities, intratumoral and intertumoral heterogeneity, and the inexorable emergence of multifaceted drug resistance mechanisms. These persistent therapeutic challenges have reinstated interest in natural products (NPs) as evolutionar

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… class | Cancer models | Key anticancer mechanisms | Reference(s) Jania rubens | Egypt, Lebanon | Methanolic extract | Phenolics; terpenoids | Colorectal cancer | ROS modulation; cell cycle arrest | ( 201 ) Aspergillus fumigatus (WA7S6) | Egypt (Red Sea sponge microbiome) | Fatty acids; dehydromevalonic lactone … | Fatty acids; lactones | Breast; cervical cancer | HO-1 inhibition; apoptosis induction | ( 203 ) Aspergillus niger | Egypt (Red Sea coast) | Organic acids (oxalic, citric acid derivatives) | Organic acids | Breast; liver; colon cancer | Oxidative stress modulation; cytotoxicity | ( 204 ) Sesamum indicum …

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles publ

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen s

Autophagic mechanisms in longevity intervention: role of natural active compounds.

The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m

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… ROS production | (Ref. 164 ) Polyphenols | Curcumin | Pancreatic cancer (PANC1, BxPC3) | Autophagy induction | Increases autophagosomes | (Ref. 165 ) Polyphenols | Curcumin | Prostate cancer (PC3, DU145, LNCaP) | Autophagy as epigenetic regulator | Inhibits DNMT1 and DNMT3B | (Ref. 166 ) Steroidal lactones … Withaferin A had a steroidal lactone structure and inhibited lysosomal activity to block autophagic flux in breast cancer cells (Ref. 167 ). Periplocin is a natural active steroid isolated from Periploca forrestii Schltr. (Apocynaceae). …

Bioinformatics-Guided Discovery of miRNAs Involved in Apoptosis Modulated by Parthenolide Combined with Vincristine in The NALM6 Cell Line.

ObjectiveAcute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the Tanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induce apoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone on the apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line.Materials and met

Predictive Modeling of Pharmacokinetic Drug-Drug and Herb-Drug Interactions in Oncology: Insights From PBPK Studies.

Physiologically based pharmacokinetic (PBPK) modeling is increasingly used to anticipate, quantify, and strategically manage drug-drug (DDI) and herb-drug (HDI) interactions that can alter the exposure of chemotherapy agents together with co-administered phytochemicals or nutraceuticals. To evaluate current knowledge, we performed a comprehensive Google Scholar search (2003-2024) and selected studies that employed PBPK platforms, reported quantitative validation, and focused on chemotherapy-related interactions. From these reports, key modeling parameters, validation metrics, and clinically re

Синергическое регенеративное, иммунодуляционное и антивоспалительное воздействие ваниллина и адипозы производных стволовых клеток в животной модели купризонного склероза.

ЦЕЛИ: Ваниллин как потенциальный терапевтический агент наряду с трансплантацией нейротрофических факторов, отделяющих клетки, считается перспективным средством лечения неврологических расстройств. В этом исследовании последствия ваниллина в сочетании с трансплантацией стволовых клеток, полученных человеком, были оценены с точки зрения дифференциации олигодендроцитов, повторного сглаживания и улучшения моторных функций. МАТЕРИАЛЫ И МЕТОДЫ: Женский C57BL/6 Мышей кормили кухонной зоной.400 мг/кг/сут.) 5 неделями, чтобы вызвать MS. Демилинированные мыши были разделены на группы MS, MS/vanillin, MS

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- a

Manifestations of systemic disease in the retina and fundus of cats and dogs.

The fundus is unique in that it is the only part of the body that allows for a noninvasive and uninterrupted view of vasculature and nervous tissue. Utilization of this can be a powerful tool in uncovering salient incidental findings which point to underlying systemic diseases, and for monitoring response to therapy. Retinal venules and arterioles allow the clinician to assess changes in vascular color, diameter, outline, and tortuosity. The retina and optic nerve may exhibit changes associated with increased or decreased thickness, inflammatory infiltrates, hemorrhages, and detachments. While

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… Cats and dogs with defects in the ABCB1 gene (formerly MDR1 ) may present with severe concurrent signs of neurotoxicity when exposed to macrocyclic lactones (e.g., avermectins and milbemycins) ( 171 , 172 , 175 ). …

Toxicology and Carcinogenesis Studies of 8-Methoxypsoralen (CAS No. 298-81-7) in F344/N Rats (Gavage Studies).

Oral administration of 8-methoxypsoralen followed by exposure to longwave ultraviolet light (primarily ultraviolet A, 320-400 nm) is used in the treatment of vitiligo and psoriasis. 8-Methoxypsoralen also occurs naturally in a variety of vegetables. Toxicology and carcinogenesis studies of 8-methoxypsoralen without ultraviolet A were conducted by administering USP-grade 8-methoxypsoralen (99% pure) in corn oil by gavage to groups of F344/N rats once or for 16 days, 13 weeks, or 2 years. In vitro genetic toxicology tests were performed with bacteria and mammalian cells. Single-Administration, S

Oxidized Lipids in Persistent Pain States.

Chemotherapy, nerve injuries, or diseases like multiple sclerosis can cause pathophysiological processes of persistent and neuropathic pain. Thereby, the activation threshold of ion channels is reduced in peripheral sensory neurons to normally noxious stimuli like heat, cold, acid, or mechanical due to sensitization processes. This leads to enhanced neuronal activity, which can result in mechanical allodynia, cold allodynia, thermal hyperalgesia, spontaneous pain, and may initiate persistent and neuropathic pain. The treatment options for persistent and neuropathic pain patients are limited; f

Progress on new drug treatments for hepatic echinococcosis.

Echinococcosis: is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus tapeworms. At present, the standardized treatment regimen for this disease consists of radical lesion resection combined with albendazole. For patients who are inoperable or experience postoperative recurrence, the treatment with anti-echinococcosis drugs is particularly crucial. To date, albendazole remains the primary drug clinically used for anti-echinococcosis treatment. However, it has inherent drawbacks such as low bioavailability, poor solubility, long treatment course, and multiple adver

HMGB1 enhances chemotherapy resistance in multiple myeloma cells by activating the nuclear factor-κB pathway.

Chemotherapy resistance is a main obstacle in the clinical chemotherapeutic treatment of multiple myeloma (MM). High-mobility group box 1 (HMGB1) has been revealed to be associated with the sensitivity of MM cells to chemotherapy, but how HMGB1 regulates chemotherapy resistance in MM has yet to be fully elucidated. In the present study, the exact molecular mechanism underlying HMGB1-mediated drug resistance in MM was explored using three chemotherapy-resistant MM cells (RPMI8226/ADR, RPMI8226/BOR and RPMI8226/DEX) that were successfully established. Reverse transcription-quantitative polymeras

Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid leukemia.

Drug resistance and human leukocyte antigen (HLA) matching limit conventional treatment of acute myeloid leukemia (AML). Although several small molecule drugs are clinically used, single drug administration is not sufficient to cure AML, which has a high molecular diversity. Metabolic homeostasis plays a key role in determining cellular fate. Appropriate levels of reactive oxygen species (ROS) maintain the redox system balance, and excessive amounts of ROS cause oxidative damage, thus providing a strategy to eliminate cancer cells. CPPTL is a novel analogue of parthenolide that exhibited signi

Bortezomib treatment causes long-term testicular dysfunction in young male mice.

BackgroundWith increased long-term survivors of childhood cancer patients, therapy-associated infertility has become one of the most common late side-effects and significantly affects their life-quality. Therefore, evaluation of anti-cancer agents on male reproduction and infertility prevention are urgently demanding. The proteasome inhibitor bortezomib has been launched in clinical trials for childhood cancers, however, its potential side effects on reproduction have so far been neither investigated experimentally nor reported in treated children. Thus the present study is designed to explore

Promising Activities of Marine Natural Products against Hematopoietic Malignancies.

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially avai

Immediate and delayed VEGF-mediated NO synthesis in endothelial cells: role of PI3K, PKC and PLC pathways.

1. The mechanism(s) by which vascular endothelial growth factor (VEGF) induces endothelial nitric oxide synthase (eNOS) activation remain(s) unclear up to a certain extent. Therefore, we sought to evaluate the contribution of numerous pathways in VEGF-induced nitric oxide (NO) synthesis by measuring cGMP production. In addition, as VEGF induces the synthesis of NO and platelet-activating factor (PAF), we wanted to assess if the induction of PAF and NO is contributing to the synthesis of each other. 2. Herein, we show that a treatment of endothelial cells with a phospholipase C (PLC) inhibitor

Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.

Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and

Role of phytoconstituents in the management of COVID-19.

BackgroundCOVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas.Scope and approachThis review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry

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… somnifera binds with NSP3 [ 35 ] Anthraquinones Microcarpin Image 125 binds with TMPRSS2 [ 174 ] Anthocyanins Chry-santhemin Image 126 Black grapes RdRp and hACE-2 [ 55 ] Stilbenes δ-Viniferin Image 127 Grapevine leaves M Pro , RdRp and hACE-2 [ 55 ] Iso-gemichalcone Image 128 binds with TMPRSS2 [ 174 ] Lactones … Anthraquinones Microcarpin | Image 125 | | binds with TMPRSS2 | [ 174 ] Anthocyanins Chry-santhemin | Image 126 | Black grapes | RdRp and hACE-2 | [ 55 ] Stilbenes δ-Viniferin | Image 127 | Grapevine leaves | M Pro , RdRp and hACE-2 | [ 55 ] Iso-gemichalcone | Image 128 | | binds with TMPRSS2 | [ 174 ] Lactones …