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Allograft for Myeloma: Examining Pieces of the Jigsaw Puzzle.

Multiple myeloma (MM) cure remains elusive despite the availability of newer anti-myeloma agents. Patients with high-risk disease often suffer from early relapse and short survival. Allogeneic hematopoietic cell transplantation (allo-HCT) is an "immune-based" therapy that has the potential to offer long-term remission in a subgroup of patients, at the expense of high rates of transplant-related morbidity and mortality. Donor lymphocyte infusion (DLI) upon disease relapse after allo-HCT is able to generate an anti-myeloma response suggestive of a graft-versus-myeloma effect. Allo-HCT provides a

Early precursor T-cell acute lymphoblastic leukemia: current paradigms and evolving concepts.

Early precursor T cell-acute lymphoblastic leukemia (ETP-ALL) is a rare entity characterized by chemo-resistance and a paucity of data regarding optimal management. We review here the literature regarding the management of ETP-ALL and focus on the recent, emerging data, regarding the potential role of molecularly targeted approaches with a focus on venetoclax.

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

Myeloid Cell-Derived Arginase in Cancer Immune Response.

Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid

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… Moreover, silencing of cyclin D3 in Jurkat cells reproduces effects induced by L-arg starvation ( 232 ). Cyclin D3 was shown to be regulated by L-arg through transcriptional, posttranscriptional, and translational mechanisms ( 232 ). …

Proceedings of the CIMAGO Meeting - Challenges in Oncobiology Coimbra, 31st january 2020.

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Sp3 улучшила экспериментальный аутоиммунный энцефаломиэлит, спровоцировав Socs3 в клетках Th17.

ВВЕДЕНИЕ: Хотя считается, что хронические подстрекательские и дегенеративные заболевания центральной нервной системы поддерживаются аутоиммунными клетками ТТ17, основополагающие механизмы остаются в основном неисследованными. Недавние исследования и наши исследования показали, что Sp3 был заблокирован в нескольких склерозах (MS) и экспериментальном аутоиммунном энцефаломиелите (EAE). Вместе с тем остается неясным, почему в нем ничего не говорится и как он регулирует дифференциацию клеток TH17 в MS. ЦЕЛИ: Данное исследование было направлено на изучение воздействия Сп3 на ТХ17 в клетках EAE и ле

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… Additionally, the expression of IL-17A was downregulated in human Jurkat cells transfected with LV-anti-miR-223 ( Fig. S3 b, p  < 0.05). Classical theory suggests that the IL-6/Stat3 and TGF-β/Smad2 signaling pathways play a role in the control of Th17 cell polarization. …

The roles of osteoprotegerin in cancer, far beyond a bone player.

Osteoprotegerin (OPG), also known as tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), is a member of the tumor necrosis factor (TNF) receptor superfamily. Characterized by its ability to bind to receptor activator of nuclear factor kappa B ligand (RANKL), OPG is critically involved in bone remodeling. Emerging evidence implies that OPG is far beyond a bone-specific modulator, and is involved in multiple physiological and pathological processes, such as immunoregulation, vascular function, and fibrosis. Notably, numerous preclinical and clinical studies have been conducted to

Evidence-Based Review of BioBran/MGN-3 Arabinoxylan Compound as a Complementary Therapy for Conventional Cancer Treatment.

IntroductionConventional cancer treatment, including surgery, chemotherapy, and radiotherapy, may not be sufficient to eradicate all malignant cells and prevent recurrence. Intensive treatment often leads to a depressed immune system, drug resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3 Arabinoxylan is a standardized arabinoxylan concentrate which has been proposed as a plant-based immunomodulator that can restore the tumor-induced disturbance of the natural immune system, including natural killer cell activity to fight cancer, complementing conventional therapies.Obj

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.

The rapid emergence of resistance limits the application of proteasome inhibitors against solid tumors, despite their effectiveness in the treatment of hematological malignancies. Resistant phenotypes are complex and multifaceted, and, thus, the mechanisms involved have not been adequately described. In this study, a Bortezomib-resistant prostate cancer cell line is created by using the PC-3 cell as a prostate carcinoma model of high metastatic potential. The main biochemical differences and adaptations exhibited by the resistant cells revolve around apoptosis evasion, autophagy induction (fun

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers.

Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present sig

Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with part

Krill oil extract suppresses the proliferation of colorectal cancer cells through activation of caspase 3/9.

BackgroundCurrently available treatments for colorectal cancer (CRC) associate with numerous side-effects that reduce patients' quality of life. The effective nutraceuticals with high anti-proliferative efficacy and low side-effects are desirable. Our previous study has reported that free fatty acids extract (FFAE) of krill oil induced apoptosis of CRC cells, possibly associated with changes in mitochondrial membrane potential (MMP). The aims of this study were to compare the anti-proliferative efficacy of FFAE from krill oil on CRC cells with commonly used chemotherapeutic drug, Oxaliplatin,

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… Sanchez-Alcazar JA Ault JG Khodjakov A Schneider E Increased mitochondrial cytochrome c levels and mitochondrial hyperpolarization precede camptothecin-induced apoptosis in Jurkat cells Cell Death Differ 2000 7 11 1090 1100 11139283 10.1038/sj.cdd.4400740 60. …

Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting side effect of several antineoplastic drugs which significantly reduces patients' quality of life. Although different molecular mechanisms have been investigated, CIPN pathobiology has not been clarified yet. It has largely been recognized that Dorsal Root Ganglia are the main targets of chemotherapy and that the longest nerves are the most damaged, together with fast axonal transport. Indeed, this bidirectional cargo-specific transport has a pivotal role in neuronal function and its impairment is involved in several neurodeg

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and objectiveAnnexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help ad

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… ANXA1 has differential effects on the apoptosis of cells treated with different doses of FR235222 , a novel histone deacetylase inhibitor in human promyelocytic leukemia U937 cells, human chronic myelogenous leukemia K562 cells and human T-cell leukemia Jurkat cells ( 70 ). …

Redox Remodeling by Nutraceuticals for Prevention and Treatment of Acute and Chronic Inflammation.

Antioxidant-rich dietary regimens are considered the best practice to maintain health, control inflammation, and prevent inflammatory diseases. Yet, nutraceuticals as food supplements are self-prescribed and purchasable over the counter by healthy individuals for the purpose of beneficial effects on fitness and aging. Hence, the effectiveness, safety, and correct intake of these compounds need to be better explored. Since redox-modulating activity of these compounds appears to be involved in activation and or suppression of immune cells, the preventive use of nutraceuticals is very attractive

Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences.

Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast the

Нанотехнология в области гематологии: усиление терапевтической эффективности с помощью нанопчастей.

Фон и цели Гематологические заболевания, такие, как лейкемия, лимфома и множественная миелома, вносят значительный вклад в глобальный диагноз рака. Несмотря на прогресс в традиционных методах лечения, таких, как химиотерапия и иммунотерапия, эти методы лечения сталкиваются с ограничениями, включая неконкретную адресность, побочные эффекты и резистентность к лекарствам. Цель этого обзора заключается в изучении потенциала нанотехнологии, в частности наночастиц (НФ), для улучшения терапевтических последствий для этих раковых заболеваний путем расширения поставок наркотиков и снижения токсичности.

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… Q., “Microfluidic Assisted Nanoprecipitation of PLGA Nanoparticles for Curcumin Delivery to Leukemia Jurkat Cells,” Langmuir 34, no. 13 (April 2018): 3961–3970. 142. …

Direct Intercellular Communications and Cancer: A Snapshot of the Biological Roles of Connexins in Prostate Cancer.

Tissue homeostasis is the result of a complex intercellular network controlling the behavior of every cell for the survival of the whole organism. In mammalian tissues, cells do communicate via diverse long- and short-range communication mechanisms. While long-range communication involves hormones through blood circulation and neural transmission, short-range communication mechanisms include either paracrine diffusible factors or direct interactions (e.g., gap junctions, intercellular bridges and tunneling nanotubes) or a mixture of both (e.g., exosomes). Tumor growth represents an alteration

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… Interestingly, when the mitochondrial transfer is decreased between mesenchymal stem cells and Jurkat cells, it increases chemotherapy-induced cell death [ 39 ]. Mitochondrial transfer between bone marrow microenvironment and leukemic cells thus appears as a new mechanism of drug resistance [ 40 ]. …

Growth factor independence 1 expression in myeloma cells enhances their growth, survival, and osteoclastogenesis.

BACKGROUND: In spite of major advances in treatment, multiple myeloma (MM) is currently an incurable malignancy due to the emergence of drug-resistant clones. We previously showed that MM cells upregulate the transcriptional repressor, growth factor independence 1 (Gfi1), in bone marrow stromal cells (BMSCs) that induces prolonged inhibition of osteoblast differentiation. However, the role of Gfi1 in MM cells is unknown. METHODS: Human primary CD138+ and BMSC were purified from normal donors and MM patients' bone marrow aspirates. Gfi1 knockdown and overexpressing cells were generated by lent