Search

ObjectivesDoxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene.Materials and methodsIn the current study, different sequences of cell-penetrating peptides (CPPs) containing tryptophan, lysine, and arginine and their nano-complexes were synthesized and their impact on the expression and activity of the ABCB1 gene was evaluated in the A549 lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A549 cell line was assessed.ResultsThe designed peptides, including [W4K4], [WR]3-QGR, R10, and K10 increased Dox cytotoxicity after 48 hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin123 accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB1 gene expression, of which, [W4K4] resulted in the lowest expression ratio.Conclusion[W4K4], [WR]3-QGR, R10, and K10 could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.

Background and Aims: One of the main vital needs for self‐care in patients with advanced cancer is information need. Meeting this need has significant positive effects on improving their treatment and care. This study was conducted to identify the unmet information needs of patients with advanced cancer in Iran. Methods: This exploratory study was performed from July to February 2021 in the Kerman University of Medical Sciences cancer treatment centers. Oncologists selected eligible patients by purposeful sampling method. Semistructured and in‐depth interviews were conducted with selected patients to collect data. Interviews continued until data saturation. Each interview was audio‐recorded and transcribed verbatim. Results: In the interviews, 15 patients with advanced cancer ranging in age from 43 to 65 years participated. The most common type of cancer in women was breast (71.4%) and prostate (50%) in men. The two main categories of "types of unmet information needs" and "reasons for not meeting information needs" were extracted from the analysis of patient interviews, with six and four subcategories, respectively. Conclusion: Cancer patients had a large number of unmet information needs. At the time of identifying the unmet information needs of cancer patients, the basic reasons for not meeting these needs should also be considered because cultural differences and social gaps in societies are inevitable. [ABSTRACT FROM AUTHOR]

Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix (ECM) protein belonging to the fibrinogen-related domain superfamily. MFAP4 is highly expressed in elastin-rich tissues such as lung, blood vessels and skin. MFAP4 is involved in organization of the ECM, regulating proper elastic fiber assembly. On the other hand, during pathology MFAP4 actively contributes to disease development and progression due to its interactions with RGD-dependent integrin receptors. Both tissue expression and circulating MFAP4 levels are associated with various disorders, including liver fibrosis and cancer. In other experimental models, such as teleost fish, MFAP4 appears to participate in host defense as a macrophage-specific innate immune molecule. The aim of this review is to summarize the accumulating evidence that indicates the importance of MFAP4 in homeostasis as well as pathological conditions, discuss its known biological functions with special focus on elastic fiber assembly, integrin signaling and cancer, as well as describe the reported functions of non-mammalian MFAP4 in fish. Overall, our work provides a comprehensive overview on the role of MFAP4 in health and disease. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has made improvements due to the advances in chimaeric antigen receptor (CAR) T cell development, offering a promising treatment option for patients who have failed to respond to traditional treatments. In light of the successful use of adoptive CAR T cell therapy for cancer, researchers have been inspired to develop CARs for the treatment of other diseases beyond cancers such as viral infectious diseases. Nonetheless, various obstacles limit the efficacy of CAR T cell therapies and prevent their widespread usage. Severe toxicities, poor in vivo persistence, antigen escape, and heterogeneity, as well as off‐target effect, are key challenges that must all be addressed to broaden the application of CAR T cells to a wider spectrum of diseases. The key advances in CAR T cell treatment for cancer and viral infections are reviewed in this article. We will also discuss revolutionary CAR T cell products developed to improve and enhance the therapeutic advantages of these treatments. [ABSTRACT FROM AUTHOR]

Purpose: Sepantronium bromide (YM155) is a Survivin inhibitor which recently advanced as an anticancer agent in phase II clinical trials. Survivin belongs to IAP (inhibitor of apoptosis) gene family and is a pivotal target for treatment due to its over expression and oncogenic function in many malignancies, including acute lymphoblastic leukemia (ALL). Although survivin is a specific target for YM155, recent reports have shown that it has many other crucial targets that regulate its anti-apoptotic effects. The aim of this study was to investigate whether YM155 could have an effect on cell death-inducing genes as well as inducing apoptosis in T-ALL MOLT4-cell line. Methods: We treated MOLT-4 cells with increasing concentrations of YM155 and then cell viability was determined using MTT (methyl thiazolyl tetrazolium) assay. Also, the rate of induction of apoptosis in MOLT-4 cells and the target genes expression levels were evaluated by Annexin V/PI and real-time PCR, respectively. Results: YM155 inhibited cell growth in MOLT-4 cells. This outcome is achieved by inducing apoptosis and a significant increase in the expression level of P53, MiR-9, caspase 3 and decreasing the mRNA expression levels of survivin, Sirtuin1(SIRT1), member of anti-apoptotic proteins family (Bcl-2), and epithelial-to-mesenchymal transition (EMT) initiating factors Snail1and Zeb2. Conclusion: The results showed that use of YM155 can be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction. [ABSTRACT FROM AUTHOR]

During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators high mobility group A2 (HMGA2) and BTB and CNC homology 1 (Bach‐1) are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach‐1 promote cancer development has been limited. We found that HMGA2 and Bach‐1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach‐1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach‐1 knockdown additively decrease cell proliferation, migration, epithelial‐to‐mesenchymal transition, and colony formation, while promoting apoptotic cell death via upregulation of caspase‐3 and caspase‐9. First the first time, we show that HMGA2 and Bach‐1 overexpression in tumors correlate positively and that the proteins cooperatively suppress a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity, and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer. [ABSTRACT FROM AUTHOR]

Malignant neoplasms are regarded as the main cause of death around the world; hence, many research studies were conducted to further perceive molecular mechanisms, treatment, and cancer prognosis. Cancer is known as a major factor for health‐related problems in the world. The main challenges associated with these diseases are prompt diagnosis, disease remission classification and treatment status forecast. Therefore, progressing in such areas by developing new and optimized methods with the help of minimally invasive biological markers such as circular microRNAs (miRNAs) can be considered important. miRNA interactions with target genes have specified their role in development, apoptosis, differentiation, and proliferation and also, confirm direct miRNA function in cancer. Different miRNAs expression levels in various types of malignant neoplasms have been observed to be associated with prognosis of various carcinomas. miR‐9 seems to implement opposite practices in different tissues or under various cancer incidences by influencing different genes. Aberrant miR‐9 levels have been observed in many cancer types. Therefore, we intended to investigate the precise role of miR‐9 in patients with malignant neoplasms. To this end, in this study, we attempted to examine different studies to clarify the overall role of miR‐9 as a prognostic marker in several human tumors. The presented data in this study can help us to find the novel therapeutic avenues for treatment of human cancers. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self‐renewal capacity, low proliferation rate, and tumor‐initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. The molecular mechanisms underlying CSC biology are now beginning to be understood. In this context, microRNAs (miRNAs) occupy a prominent place. These endogenous, small noncoding RNA molecules control gene expression at the posttranscriptional level. This study reviews our current understanding of how the misexpression of tumor suppressor and oncogenic miRNAs in CSCs sustain their abundance and malignant properties. We discuss how they partly do so by acting on major CSC signaling pathways, including the Wnt, Notch, Hedgehog, and BMI‐1 pathways. Our current knowledge of miRNA functions in CSCs may now be used for cancer diagnostic and prognostic purposes. In addition, when combined with recent technical advances in the in vivo delivery of miRNAs, we are now in an excellent position to develop strategies that harness miRNA interference and replacement technologies for the therapeutic targeting of CSCs. Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. In this review article, we will discuss the involvement of specific microRNAs (miRNAs) in controlling the CSC phenotype. We will focus on how miRNAs influence the main CSC signaling pathways. Finally, we will consider the recent therapeutic strategies that target miRNAs for CSC therapeutic purpose. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of Tetraphenylporphyrin and H2T(4-SO2Cl)PP. • Conjugation of functionalized porphyrin to albumin-metronidazole nanoparticles. • In vitro radiation/photodynamic therapy. Breast cancer is the second leading cause of cancer death in women after lung cancer. In the context of cancer therapy, chemotherapy regarded as the most common method of treatment, but besides this beneficial modality, radiation therapy (RT) is used as a supplementary or palliative treatments. In this regard, we aimed at preparing albumin- Tetraphenylporphyrin -metronidazole nanosystem (BSA-Met- H2T(4-SO2)PP NPs) as an effective photo/radiosensitizer along with RT to tackle breast cancer. Accordingly, the synthesized nanosystems were analyzed by various characterization techniques such as dynamic light scattering (DLS), fourier transform infrared spectroscopy (FT-IR), UV–vis, and proton nuclear magnetic resonance (1HNMR), also transmission electron microscopy (TEM) technique was used to determine the morphology and size of fabricated nanosystems. Moreover, the biosafety of developed nanosystems were ascertained using LD 50 and hemolysis assay. Based on DLS measurements the average size and polydispersity index of fabricated nanosystems were about 190 nm and 0.36, respectively. The BSA-Met-H2T(4-SO2)PP NPs showed pH-dependent drug release behavior. The results showed that the drug loading (DL) for metronidazole and Tetraphenylporphyrin were 3.406% and 13.586%, respectively. Both hemolysis and LD 50 confirmed the biosafety of the BSA-Met-H2T(4-SO2)PP NPs. Finally, MTT assay revealed that the prepared nanoparticles exhibited great anti-cancer activity upon radiation and light against 4 T1 cancer cells. Overall, our findings suggest that PPHN-MET NPs may be promising candidates for the effective radiation/or light-induced cancer therapy. [ABSTRACT FROM AUTHOR]

Immune cells are recruited into the tumor microenvironment and regulate anti- and pro-tumor signals. MicroRNAs (miRNAs) markedly control the immune system responses in cancer development. miRNAs that affect the immune system could be interesting targets for immunomodulation against cancer, either through the activation of effector cells or through the down-regulation of regulatory cells. Bioinformatic calculations can predict the immune system and miRNA interactions. In this review, we discuss the most recent studies about miRNA as the main regulator of recruitment and the activation of the immune system in the tumor microenvironment and finally we propose several miRNAs that could serve as therapeutic molecules in the immunotherapy of cancer. [ABSTRACT FROM AUTHOR]

Anticancer drugs resistance is a complex process that arises from altering in the drug targets. Advances in the DNA microarray, proteomics technology and the development of targeted therapies provide the new strategies to overcome the drug resistance. Although a design of the new chemotherapy agents is growing quickly, effective chemotherapy agent has not been discovered against the advanced stage of cancer (such as invasion and metastasis). The cancer cell resistance against the anticancer agents can be due to many factors such as the individual's genetic differences, especially in tumoral somatic cells. Also, the cancer drug resistance is acquired, the drug resistance can be occurred by different mechanisms, including multi-drug resistance, cell death inhibiting (apoptosis suppression), altering in the drug metabolism, epigenetic and drug targets, enhancing DNA repair and gene amplification. In this review, we outlined the mechanisms of cancer drug resistance and in following, the treatment failures by common chemotherapy agents in the different type of cancers. [ABSTRACT FROM AUTHOR]

The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of development and in adulthood. Importantly, HMGA2 is re-expressed in nearly all human malignancies, where it promotes tumorigenesis by multiple mechanisms. HMGA2 increases cancer cell proliferation by promoting cell cycle entry and inhibition of apoptosis. In addition, HMGA2 influences different DNA repair mechanisms and promotes epithelial-to-mesenchymal transition by activating signaling via the MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFkB, and STAT3 pathways. Moreover, HMGA2 supports a cancer stem cell phenotype and renders cancer cells resistant to chemotherapeutic agents. In this review, we discuss these oncogenic roles of HMGA2 in different types of cancers and propose that HMGA2 may be used for cancer diagnostic, prognostic, and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Abstract MicroRNAs are post-transcriptional mediators of gene expression and regulation, which play influential roles in tumorigenesis and cancer metastasis. The expression of tumor suppressor miR-145 is reduced in various cancer cell lines, containing both solid tumors and blood malignancies. However, the responsible mechanisms of its down-regulation are a complicated network. miR-145 is potentially able to inhbit tumor cell metastasis by targeting of multiple oncogenes, including MUC1, FSCN1, Vimentin, Cadherin, Fibronectin, Metadherin, GOLM1, ARF6, SMAD3, MMP11, Snail1, ZEB1/2, HIF-1α and Rock-1. This distinctive role of miR-145 in the regulation of metastasis-related gene expression may introduce miR-145 as an ideal candidate for controlling of cancer metastasis by miRNA replacement therapy. The present review aims to discuss the current understanding of the different aspects of molecular mechanisms of miR-145 regulation as well as its role in r metastasis regulation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome. MiRNA-143 is defined as an important tumor suppressor in a variety of neoplasms including solid tumors and B-cell malignancies. MiRNA-143 is involved in the pathogenesis of cancers by directly targeting several mRNAs such as Bcl-2 , KRAS , HK2 , DNMT3A , TP53 and MMP-13 . In this study, an overview of the miRNA-143 function in different signaling pathways in cancer will be provided. [ABSTRACT FROM AUTHOR]

• Accumulation of DNA damage leads to the progression of cancer in more metastatic and invasive forms. • DNA damage response (DDR) plays a central role in maintaining genome integrity. • Autophagy, which is a physiological self-eating, has been demonstrated to be involved in DNA damage. • The interplay between DDR and autophagy may have a critical role in the pathogenesis of various malignancies. The subjection of DNA to numerous lethal damages is threatening for the stability and integrity of the whole body genome. DNA damage response (DDR) is a critical phosphorylation-based signaling pathway developed for the maintaining of the genome against these threatens. Recent studies showed that various targets of DDR are involved in the activation of autophagy, as one of the important effectors of this signaling. The interplay between DDR and autophagy may have a critical role in the pathogenesis of various malignancies such as colorectal cancer, which can be a basement for the designing novel therapeutic strategies for combating this cancer type. On the other hand, autophagy is also demonstrated to be contributed to the regulation of DDR components. Therefore, in this review article, we will discuss the crosstalk between DDR and autophagy and their exact function in the pathogenesis of various human cancer types, with special attention on colorectal cancer. [ABSTRACT FROM AUTHOR]

To protect tissues and the organism from disease, potentially harmful cells are removed through programmed cell death processes, including apoptosis and necroptosis. These types of cell death are critically controlled by microRNAs (miRNAs). MiRNAs are short RNA molecules that target and inhibit expression of many cellular regulators, including those controlling programmed cell death via the intrinsic (Bcl-2 and Mcl-1), extrinsic (TRAIL and Fas), p53-and endoplasmic reticulum (ER) stress-induced apoptotic pathways, as well as the necroptosis cell death pathway. In this review, we discuss the current knowledge of apoptosis and necroptosis pathways and how these are impaired in cancer cells. We focus on how miRNAs disrupt apoptosis and necroptosis, thereby critically contributing to malignancy. Understanding which and how miRNAs and their targets affect cell death pathways could open up novel therapeutic opportunities for cancer patients. Indeed, restoration of pro-apoptotic tumor suppressor miRNAs (apoptomiRs) or inhibition of oncogenic miRNAs (oncomiRs) represent strategies that are currently being trialed or are already applied as miRNA-based cancer therapies. Therefore, better understanding the cancer type-specific expression of apoptomiRs and oncomiRs and their underlying mechanisms in cell death pathways will not only advance our knowledge, but also continue to provide new opportunities to treat cancer. Image 1 • MicroRNA as regulatory molecules in the intrinsic and extrinsic apoptosis pathway. • MicroRNAs as regulatory molecules in apoptosis by targeting p53. • MicroRNA regulate ER stress-induced apoptosis. • MicroRNA regulate programmed necrotic cell death. [ABSTRACT FROM AUTHOR]

Background Metastasis to distant organs is a hallmark of many tumor cells. BACH1 (BTB and CNC homology 1) is a transcriptional factor which promotes the migration and invasion of breast cancer cells. BACH1 expression and its target genes are intimately associated with the metastasis possibility of clinical samples, and BACH1 reduction leads to meaningful depletion in metastasis. The evaluation of BACH1 role in colon cancer remains elusive. This study seeks to further investigate the role of BACH1 in colon cancer cells. Methods Quantitative RT-PCR (qRT-PCR) was used to detect BACH1 expression and other related metastatic genes following siRNA knockdown in colon cancer HT-29 cells. And the protein level assessed by Western blot. MTT assay was to measure the changed cell viability after BACH1 siRNA transfection. Scratch-wound motility assays measured capacity of tumor cell migration of HT-29 cells after BACH1 silencing. Results The inhibitory effect of BACH1 was performed by siRNA knockdown using highly metastatic HT-29 colon cell lines. Quantitative RT-PCR and Western blot analysis revealed that the expression levels of BACH1 mRNA and protein in HT29 cells were significantly suppressed after transfection. Conversely, the BACH1 expression increased migration. Also the CXCR4 and MMP1 expression levels decreased following BACH1 knockdown in HT-29 cells. Conclusion Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment. [ABSTRACT FROM AUTHOR]