A CD38-directed, single-chain T-cell engager targets leukemia stem cells through IFN-γ-induced CD38 expression.

Treatment resistance of leukemia stem cells (LSCs) and suppression of the autologous immune system represent major challenges to achieve a cure in acute myeloid leukemia (AML). Although AML blasts generally retain high levels of surface CD38 (CD38pos), LSCs are frequently enriched in the CD34posCD38neg blast fraction. Here, we report that interferon gamma (IFN-γ) reduces LSCs clonogenic activity and induces CD38 upregulation in both CD38pos and CD38neg LSC-enriched blasts.

Cancer-associated immune cells and their modulation by melatonin.

Objectives: Rapidly growing evidence suggests that immune cells play a key role in determining tumor progression. Tumor cells are surrounded by a microenvironment composed of different cell populations including immune cells. The cross talk between tumor cells and the neighboring microenvironment is an important factor to take into account while designing tumor therapies.

Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2022 ASH annual meeting.

Venetoclax (VEN), the first selective Bcl-2 inhibitor, has shown efficacy and safety both as monotherapy and in combination with other agents in the treatment of newly diagnosed acute myeloid leukemia (AML), while its role in relapsed or refractory (R/R) disease is not well defined. Here, we reviewed the latest advances of VEN-based therapy for R/R AML from the 2022 American Society of Hematology (ASH) Annual Meeting, including some novel and encouraging regimes, such as VCA, VAH, and HAM regimes, etc. Further research is still needed to fully understand the optimal use of these agents in R/R AML treatment.

Virtual screening reveals aprepitant to be a potent inhibitor of neutral sphingomyelinase 2: implications in blockade of exosome release in cancer therapy.

Purpose: Exosomes are membrane-derived nano-vesicles upregulated in pathological conditions like cancer. Therefore, inhibiting their release is a potential strategy for the development of more efficient combination therapies. Neutral sphingomyelinase 2 (nSMase2) is a key component in exosome release; however, a clinically safe yet efficient nSMase2 inhibitor remains to be used discovered.

The prognostic role of miR-31 in colorectal cancer: the results of a meta-analysis of 4720 patients.

To study the association between miR-31 expression and clinical outcomes in colorectal cancer. A systematic search was performed and 16 studies were found eligible. To calculate the combined hazard ratio (HR), the DerSimonian and Laird random-effects model was used.

The therapeutic triad of extracellular vesicles: As drug targets, as drugs, and as drug carriers.

Rapidly growing interest in the study of extracellular vesicles (EVs) has led to the accumulation of evidence on their critical roles in various pathologies, as well as opportunities to design novel therapeutic EV-based applications. Efficiently exploiting the constantly expanding knowledge of the biology and function of EVs requires a deep understanding of the various possible strategies of using EVs for therapeutic purposes. Accordingly, in the present work, we have narrowed the broad therapeutic potential of EVs and consider the similarities and differences of various strategies as we articulate three major aspects (i.

Inhibition of Exosome Release Sensitizes U937 Cells to PEGylated Liposomal Doxorubicin.

Aims: Acute myeloblastic leukemia (AML) is the most common type of acute leukemia in adults. Despite numerous treatment strategies including chemotherapy and radiotherapy, a large number of patients do not respond to treatment and experience relapse. The main problem of these patients is the development of resistance to anti-cancer drugs.

Exosomal microRNA panels as biomarkers for hematological malignancies.

Hematological malignancies are classified as a heterogeneous category of cancers with various degrees of incidence and prognosis and different etiologies. Due to their aggressive essence they should be diagnosed as early as possible to improve prognosis, treatment outcome and survival. Bases on the limitations of previously identified biomarkers in terms of sensitivity, specificity and predictability, it is necessary to develop new diagnostic tools and biomarkers for the early diagnosis of hematological malignancies.

Therapeutic targets of cancer drugs: Modulation by melatonin.

The biological functions of melatonin range beyond the regulation of the circadian rhythm. With regard to cancer, melatonin's potential to suppress cancer initiation, progression, angiogenesis and metastasis as well as sensitizing malignant cells to conventional chemo- and radiotherapy are among its most interesting effects. The targets at which melatonin initiates its anti-cancer effects are in common with those of a majority of existing anti-cancer agents, giving rise to the notion that this molecule is a pleiotropic agent sharing many features with other antineoplastic drugs in terms of their mechanisms of action.

Long-chain polyunsaturated omega-3 fatty acids reduce multiple myeloma exosome-mediated suppression of NK cell cytotoxicity.

Background: Despite the advances in the treatment of multiple myeloma (MM), complete remission is usually challenging. The interactions between tumor and host cells, in which exosomes (EXs) play critical roles, have been shown to be among the major deteriorative tumor-promoting factors herein. Therefore, any endeavor to beneficially target these EX-mediated interactions could be of high importance.

The mechanisms of cellular crosstalk between mesenchymal stem cells and natural killer cells: Therapeutic implications.

Mesenchymal stem cells (MSCs) are mesenchymal precursors of various origins, with well-known immunomodulatory effects. Natural killer (NK) cells, the major cells of the innate immune system, are critical for the antitumor and antiviral defenses; however, in certain cases, they may be the main culprits in the pathogenesis of some NK-related conditions such as autoimmunities and hematological malignancies. On the other hand, these cells seem to be the major responders in beneficial phenomena like graft versus leukemia.

Targeting Hippo signaling pathway by phytochemicals in cancer therapy.

The current era of cancer research has been continuously advancing upon identifying novel aspects of tumorigenesis and the principal mechanisms behind the unleashed proliferation, invasion, drug resistance and immortality of cancer cells in hopes of exploiting these findings to achieve a more effective treatment for cancer. In pursuit of this goal, the identification of the first components of an extremely important regulatory pathway in Drosophila melanogaster that largely determines cell fate during the developmental stages, ended up in the discovery of the highly sophisticated Hippo signaling cascade. Soon after, it was revealed that deregulation of the components of this pathway either via mutations or through epigenetic alterations can be observed in a vast variety of tumors and these alterations greatly contribute to the neoplastic transformation of cells, their survival, growth and resistance to therapy.

EPA and DHA have selective toxicity for PBMCs from multiple myeloma patients in a partly caspase-dependent manner.

Poly-unsaturated fatty acids (PUFAs) have been shown to have cytotoxic effects in both solid and non-solid tumors. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among the most studied PUFAs. The aim of the present study was to evaluate the cytotoxic effects of these two fatty acids (FAs) in the peripheral blood mononuclear cells (PBMCs) obtained from untreated patients (new cases) with confirmed symptomatic multiple myeloma (MM).

The emerging role of exosomes in multiple myeloma.

Multiple myeloma (MM), one of the most prevalent hematological malignancies, accounts for approximately 10% of all blood cancers. In spite of the recent advancements in MM therapy, this malignancy of terminally differentiated plasma cells (PCs) continues to remain a hard-to-cure disease due to the emergence of drug resistance and frequent relapses. It is now well-established that the tumor-supportive involvement of the bone marrow microenvironment (BMM) including the cellular and non-cellular elements are the major causes behind treatment failures of MM as well as its main complications such as osteolytic bone loss.

Inhibiting exosomal MIC-A and MIC-B shedding of cancer cells to overcome immune escape: new insight of approved drugs.

Our knowledge of the role of innate immunity in protecting against cancers has expanded greatly in recent years. An early focus was on the adoptive transfer of natural killer (NK) cells and, although this approach has demonstrated promising results in many patients, a few limitations including immune escape of tumors from cytotoxic killing by NK cells have caused treatment failures. Downregulation of the expression of activating ligands on the surface of cancer cells and prevention of the activity of soluble factors are among the mechanisms employed by cancer cells to overcome NK-mediated immunity.

Doxorubicin and liposomal doxorubicin induce senescence by enhancing nuclear factor kappa B and mitochondrial membrane potential.

Aims: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency.

Immunoregulatory role of melatonin in cancer.

Melatonin is a ubiquitous indole amine that plays a fundamental role in the regulation of the biological rhythm. Disrupted circadian rhythm alters the expression of clock genes and deregulates oncogenes, which finally promote tumor development and progression. An evidence supporting this notion is the higher risk of developing malignancies among night shift workers.

NLRP inflammasome as a key role player in the pathogenesis of environmental toxicants.

Exposure to environmental toxicants (ET) results in specific organ damage and auto-immune diseases, mostly mediated by inflammatory responses. The NLRP3 inflammasome has been found to be the major initiator of the associated pathologic inflammation. It has been found that ETs can trigger all the signals required for an NLRP3-mediated response.

Reduction of marginal mass required for successful islet transplantation in a diabetic rat model using adipose tissue-derived mesenchymal stromal cells.

Background Aims: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs), widely known as multipotent progenitors, release several cytokines that support cell survival and repair. There are in vitro and in vivo studies reporting the regenerative role of AT-MSCs possibly mediated by their protective effects on functional islet cells as well as their capacity to differentiate into insulin-producing cells (IPCs).

Methods: On such a basis, our goal in the present study was to use three different models including direct and indirect co-cultures and islet-derived conditioned medium (CM) to differentiate AT-MSCs into IPCs and to illuminate the molecular mechanisms of the beneficial impact of AT-MSCs on pancreatic islet functionality.

Modifying exosome release in cancer therapy: How can it help?

The reciprocal interactions of cancer cells with their microenvironment constitute an inevitable aspect of tumor development, progression and response to treatment in all cancers. Such bilateral transactions also serve as the key scenario underlying the development of drug resistance in many cases finally determining the fate of the disease and survival. In this view, a class of extracellular vesicles (EV) known as exosomes (EX) have been shown in the past few years to be important mediators of local and remote cell-to-cell contact changing the activity of their target cells by introducing their content of proteins, non-coding RNAs, and membrane-associated small molecules.

What Immunological Defects Predispose to Non-tuberculosis Mycobacterial Infections?

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations.

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both and , following a partially selective manner.

Does the use of melatonin overcome drug resistance in cancer chemotherapy?

Our knowledge regarding the implications of melatonin in the therapy of numerous medical conditions, including cancer is constantly expanding. Melatonin can variably affect cancer pathology via targeting several key aspects of any neoplastic condition, including the very onset of carcinogenesis as well as tumor growth, differentiation, and dissemination. Numerous studies have examined the effects of melatonin in the context of various cancers reporting the enhanced efficacy of chemo/radiotherapy in combination with this compound.