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Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells by NEO214, Perillyl Alcohol Conjugated to Rolipram.

Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of

A Comparison of the Efficacy and Safety of Denosumab and Zoledronic Acid in Patients with Bone Metastatic Breast Cancer Receiving CDK4/6 Inhibitor Therapy.

Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cord compression, or hypercalcemia. Bone-modifying agents (BMAs), such as denosumab and zoledronic acid, are crucial in reducing the frequency and severity of SREs. The inhibition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has emerged as the standard treatment for hormone receptor-positive metastatic breast cancer, demonstrating significant im

miR-708-5p: a microRNA with emerging roles in cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression post-transcriptionally. They are crucial for normal development and maintaining homeostasis. Researchers have discovered that dysregulated miRNA expression contributes to many pathological conditions, including cancer. miRNAs can augment or suppress tumorigenesis based on their expression and transcribed targetome in various cell types. In recent years, researchers have begun to identify miRNAs commonly dysregulated in cancer. One recently identified miRNA, miR-708-5p, has been shown to have profound roles in

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… CDKN2B is a tumor suppressor that forms a complex with cyclin-dependent kinase4/6 (CDK4/6) to prevent cell cycle progression through cyclin D activation of CDK4/6 [ 100 , 101 ]. CDKN2B is highly expressed in normal colon tissues but is suppressed in almost all colon tumors [ 102 ]. …

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… | - | ↓ | IGFBP-5, Wnt/β-catenin | [ 170 ] HCT116 | ↓ | ↑ | ↓ | - | MMP-2, EMT | [ 171 ] Cervical cancer | SiHa | ↓ | ↑ | ↓ | ↓ | Caspase, MMP-2, MMP-9 | [ 172 ] Gallbladder cancer | SGC-996 | ↓ | ↑ | - | - | Caspase, PARP, mitochondria | [ 173 ] Pancreatic cancer | PaCa | ↓ | - | - | ↓ | P21, p27, cyclin … D | [ 174 ] Ovarian cancer | OVCAR-3, A2780 | ↓ | ↑ | - | ↓ | Wnt, E-cadherin, cyclin D, c-myc | [ 175 ] Ned-19 | | | | | | | Bladder cancer | T24 | - | - | ↓ | - | Endocytic recycling | [ 51 ] Hepatic carcinoma | Huh7 | - | - | ↓ | - | Endocytic recycling | [ 51 ] Breast cancer | 4T1 | - | - …

Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence.

Chemoprevention is referred to as a strategy to inhibit, suppress, or reverse tumor development and progression in healthy people along with high-risk subjects and oncologic patients through using pharmacological or natural substances. Numerous phytochemicals have been widely described in the literature to possess chemopreventive properties, although their clinical usefulness remains to be defined. Among them, caryophyllane sesquiterpenes are natural compounds widely occurring in nature kingdoms, especially in plants, fungi, and marine environments. Several structures, characterized by a commo

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

Тематический анализ прогноза, диагностики и терапии циркулирующих биомаркеров миРНА в борцезомибно-стойких миеломах.

ЦЕЛЬ: Растущий спрос на точную медицину стимулировал молекулярные диагностические исследования, с тем чтобы подчеркнуть полезность микроРНК в качестве важных биомаркеров. В недавних исследованиях подчеркивается роль МИРНА как перспективных, диагностических и терапевтических биомаркеров в управлении и мониторинге нескольких пациентов, страдающих миеломой. Цель этого обзора заключается в том, чтобы представить последние сведения о потенциале распространения миРНА в качестве прогнозирующих, диагностических и терапевтических биомаркеров в нескольких миеломах, устойчивых к бортезомибу. МЕТОДЫ: С эт

MM-129 as a Novel Inhibitor Targeting PI3K/AKT/mTOR and PD-L1 in Colorectal Cancer.

Background and aimsThe purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer.MethodsMM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis.ResultsThe results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29

Множественная миелома высокого риска: от молекулярной классификации к новаторскому лечению с помощью Моноклональных антител и режиссёрской терапии Т-Келл.

Большие генетические миеломы по-прежнему являются серьезной терапевтической проблемой, поскольку пациенты, имеющие неблагоприятные генетические аномалии, такие, как дель(17p), TP53 мутации и biallelic del(1p32), по-прежнему сталкиваются с плохими результатами, несмотря на недавние терапевтические достижения. В рамках этого обзора изучаются меняющиеся определения и молекулярные характеристики HRMM с уделением особого внимания последним обновленным данным о стратегиях стратификации и лечения рисков. Новая генетическая классификация, предложенная на 2025 Совещание ЕММА обеспечивает более высокую

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… In particular, CDKN2A, together with CDKN2B, CDKN2C, and CDKN2D, regulates cell proliferation by inhibiting the activity of cyclin D–CDK complexes [ 49 ]. …

Repurposed Drugs in Gastric Cancer.

Gastric cancer (GC) is one of the major causes of death worldwide, ranking as the fifth most incident cancer in 2020 and the fourth leading cause of cancer mortality. The majority of GC patients are in an advanced stage at the time of diagnosis, presenting a poor prognosis and outcome. Current GC treatment approaches involve endoscopic detection, gastrectomy and chemotherapy or chemoradiotherapy in an adjuvant or neoadjuvant setting. Drug development approaches demand extreme effort to identify molecular mechanisms of action of new drug candidates. Drug repurposing is based on the research of

Biological and clinical aspects of HPV-related cancers.

Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly

Transcriptome Meta-Analysis of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with varying responses to neoadjuvant chemotherapy (NAC). The identification of biomarkers to predict NAC response and inform personalized treatment strategies is essential. In this study, we conducted large-scale gene expression meta-analyses to identify genes associated with NAC response and survival outcomes. The results showed that immune, cell cycle/mitotic, and RNA splicing-related pathways were significantly associated with favorable clinical outcomes. Furthermore, we integrated and divided the gene association results from

Clinicopathological Features and Prognostic Differences Between Primary and Relapsed or Refractory Extramedullary Multiple Myeloma.

PURPOSE: This study aims to explore the clinicopathological features related to extramedullary multiple myeloma (EMM) occurrence and evaluate prognosis differences between patients with primary EMM (PEMM) and those with relapsed or refractory EMM (R/REMM). PATIENTS AND METHODS: The laboratory test results, clinical, histopathological and immunophenotypic characteristics, cytogenetic changes and prognosis of 203 patients with MM were obtained. The patients were categorized into EMM+ and EMM- groups. Patients in the EMM+ group were further categorized into the PEMM and R/REMM groups based on th

Cancer-Related Alopecia Risk and Treatment.

Opinion statementCancer-related alopecia (CRA) presents a significant challenge for many patients undergoing cancer treatment, often affecting their psychological well-being and sense of identity. In my opinion, the optimal management of CRA requires a proactive, personalized approach that prioritizes both prevention and regrowth, while taking into account the type of cancer therapy, patient goals, and overall clinical context. For patients receiving chemotherapy, especially taxane- or anthracycline-based regimens, scalp cooling should be offered as a first-line preventative option whenever fe

Nature-Inspired Strategies in Cancer Management: The Potential of Plant Extracts in Modulating Tumour Biology.

Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer p

Репрессии на цикле синергии со стороны HDAC/EZH2 H3K27-altered диффузная средняя глиома.

Diffuse midline glioma (DMG) — агрессивная хитрость под воздействием H3K27M онкохистоуна, приводящая к глобальному эпигенетическому регулированию и ограниченной эффективности одноагентной эпигенетической терапии. Ранее мы наблюдали клиническую выгоду от ингибитора HDAC/EZH2, но механистическая основа была неясной. Для принятия ответных мер в связи с наркотиками и проведения функциональных анализов использовалась группа культур ДИМ-глиомы стволовых клеток (ГНК) от опухолей головного мозга и спинного мозга, при этом репрезентативные модели были дополнительно проанализированы на предмет транскрип

E2112: randomized phase iii trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer.

Endocrine therapies are effective in the treatment of hormone receptor (HR)-positive breast cancer, however, de novo or acquired treatment resistance is a significant clinical problem. A potential mechanism of resistance involves changes in gene expression secondary to epigenetic modifications, which might be reversed with the use of histone deacetylase (HDAC) inhibitors such as entinostat. The ENCORE 301 phase II randomized, placebo-controlled study demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS), with the addition of entinostat to exemestan

Multiple myeloma with presentation in the oral cavity.

Plasma cell neoplasms may present in the bone as monoclonal gammopathy of undetermined significance, solitary plasmacytoma of bone, multifocal plasma cell neoplasm of bones known as multiple myeloma (MM) and in soft tissues as extramedullary plasmacytoma. MM is a malignant disease of atypical plasma cells characterized by their multifocal proliferation and production of monoclonal immunoglobulins. Often, the initial clinical feature of this disease is subtle and requires trained primary health-care providers to identify this illness and put together a suitable treatment plan. This case report

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… These are called Bence-Jones proteins, which have a characteristic property of coagulating when heated to 50°C but redissolve at 70°C.[ 7 ] Some of the molecular alterations associated with progression and unfavorable prognosis of disease are activation of one of the three cyclin D genes, translocations …

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

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… Soprano et al. reported slight accumulation of breast cancer cells in the G1 phase following treatment with nelfinavir for 24 h, associated with a clear reduction in cell cycle regulatory proteins cyclin D, E, A, B and phospho-Rb, and with an increase in the cell cycle inhibitory protein p21; strikingly …

Biological Roles and Mechanisms of Circular RNA in Human Cancers.

Circular RNA (circRNA) is an intriguing class of RNA with covalently closed-loop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated a