Emerging immunologic approaches as cancer anti-angiogenic therapies.

Targeting tumor angiogenesis, the formation of new blood vessels supporting cancer growth and spread, has been an intense focus for therapy development. However, benefits from anti-angiogenic drugs like bevacizumab have been limited by resistance stemming from activation of compensatory pathways. Recent immunotherapy advances have sparked interest in novel immunologic approaches that can induce more durable vascular pruning and overcome limitations of existing angiogenesis inhibitors. This review comprehensively examines these emerging strategies, including modulating tumor-associated macrophages, therapeutic cancer vaccines, engineered nanobodies and T cells, anti-angiogenic cytokines/chemokines, and immunomodulatory drugs like thalidomide analogs. For each approach, the molecular mechanisms, preclinical/clinical data, and potential advantages over conventional drugs are discussed. Innovative therapeutic platforms like nanoparticle delivery systems are explored. Moreover, the importance of combining agents with distinct mechanisms to prevent resistance is evaluated. As tumors hijack angiogenesis for growth, harnessing the immune system's specificity to disrupt this process represents a promising anti-cancer strategy covered by this review.

Umbilical cord mesenchymal stem cells: A powerful fighter against colon cancer?

Colon cancer (CC) stands as one of the most common malignancies related to the gastrointestinal system, whose increasing incidence and death rates have been reported all over the world. Standard treatments for fighting cancers like CC comprise surgical approaches, chemotherapy, and radiotherapy, which are suggested by clinicians according to patients' conditions and disease stages. However, patients who utilize these modalities may suffer from serious side effects and adverse outcomes, for example, toxicity and tumor recurrence, as well as a low 5-year survival rate. The present shreds of evidence showed that mesenchymal stem cells (MSCs) can have a suitable capacity for treating different health problems, especially neoplasms. These multipotent stem cells can be isolated from several sources, such as the umbilical cord, bone marrow, adipose tissue, and placenta. Among these mesenchymal sources, umbilical cord-MSCs have gathered much attention in scientific societies due to their advantages (e.g., low immunogenicity, lack of ethical problems, and easy collection). These days, the efficacy of umbilical cord-MSCs and umbilical cord-MSCs-based strategies, such as conditioned medium, extracellular vesicles, and exosomes, on CC have been explored, and promising findings have been stated. Therefore, in this review, we aimed to summarize and debate evidence regarding the effects of UC-MSCs and their related products on CC with a focus on molecular and cellular mechanisms involved in its treatment and pathogenesis of this malignant tumor.

Umbilical cord mesenchymal stem cells and lung cancer: We should be hopeful or hopeless?

Lung cancer (LC) is one of the leading causes of cancer-caused death that possesses a poor prognosis and low survival rate worldwide. In general, LC is classified into small-cell (SCLC) and non-small-cell carcinoma (NSCLC) (involving 80% of patients). Although chemotherapy, radiotherapy, surgery, and molecular-targeted therapy are considered standard approaches for LC treatment, these options have low success with detrimental effects on the life quality of patients. Ergo, recommending treatment with maximum effectiveness and minimum side effects for LC patients has been a substantial challenge for researchers and clinicians in the present era. Recently, mesenchymal stem cells (MSCs)-based strategies have sparked much interest in preventing or treating numerous illnesses. These multipotent stem cells can be isolated from diverse sources, such as umbilical cord, bone marrow, and adipose tissue. Among these sources, umbilical cord mesenchymal stem cells (UC-MSCs) have been in the spotlight of MSCs-based therapies thanks to their considerable advantages, such as high proliferation ability, low immune reactions and tumorigenesis, and easiness in collection and isolation. Some experimental studies have investigated the functionality of intact UC-MSCs and extracellular vesicles, exosomes, and conditioned medium derived from UC-MSCs, as well as genetically engineered UC-MSCs. In this review, we aimed to highlight the influences of these UMSCs-based methods in LC treatment with cellular and molecular insights.

Noncoding RNAs and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high death rate in the world. The molecular mechanisms related to the pathogenesis of HCC have not been precisely defined so far. Hence, this review aimed to address the potential cross-talk between noncoding RNAs (ncRNAs) and programmed cell death in HCC. All related papers in the English language up to June 2023 were collected and screened. The searched keywords in scientific databases, including Scopus, PubMed, and Google Scholar, were HCC, ncRNAs, Epigenetic, Programmed cell death, Autophagy, Apoptosis, Ferroptosis, Chemoresistance, Tumor recurrence, Prognosis, and Prediction. According to the reports, ncRNAs, comprising long ncRNAs, microRNAs, circular RNAs, and small nucleolar RNAs can affect cell proliferation, migration, invasion, and metastasis, as well as cell death-related processes, such as autophagy, ferroptosis, necroptosis, and apoptosis in HCC by regulating cancer-associated genes and signaling pathways, for example, phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase/MAPK, and Wnt/ß-catenin signaling pathways. It seems that ncRNAs, as epigenetic regulators, can be utilized as biomarkers in diagnosis, prognosis, survival and recurrence rates prediction, chemoresistance, and evaluation of therapeutic response in HCC patients. However, more scientific evidence is suggested to be accomplished to confirm these results.

Does crocin create new hope for the treatment of oral problems? A focus on periodontitis.

According to the World Health Organization (WHO) reports, oral health has an indispensable role in the maintenance of human public health. However, oral problems, especially periodontitis, are known as bad players in this issue. Periodontitis, as the most prevalent oral disease, is a type of chronic illness mediated by bacterial pathogens and immune system reactions, which is linked with the destruction of tooth-protecting tissues, such as alveolar bone and periodontal ligament. Periodontitis has a high prevalence (over 40% in the United States) and can be associated with other systemic ailments, for instance, arthritis, osteoporosis, metabolic syndrome, cancer, respiratory diseases, chronic kidney disease, and Alzheimer's disease. The common treatments for periodontitis are classified into invasive (surgical) and noninvasive (antibiotic therapy, scaling, and root planning) methods; however, these therapies have not reflected enough effectiveness for related patients. New documents inform the beneficial effects of plant-based compounds in healing various disorders, like periodontitis. In conjunction with this subject, it has been revealed that crocin, as an active component of saffron, regulates the balance between osteoclasts and osteoblasts and has a stroking role in the accumulation of the most common collagen in teeth and bone (type 1 collagen). Besides, this carotenoid compound possesses anti-inflammatory and anti-oxidative effects, which can be associated with the therapeutic processes of crocin in this oral disease. Hence, this narrative review study was performed to reflect the reparative/regenerative aspects of crocin agonist periodontitis.

Harnessing function of EMT in cancer drug resistance: a metastasis regulator determines chemotherapy response.

Epithelial-mesenchymal transition (EMT) is a complicated molecular process that governs cellular shape and function changes throughout tissue development and embryogenesis. In addition, EMT contributes to the development and spread of tumors. Expanding and degrading the surrounding microenvironment, cells undergoing EMT move away from the main location. On the basis of the expression of fibroblast-specific protein-1 (FSP1), fibroblast growth factor (FGF), collagen, and smooth muscle actin (-SMA), the mesenchymal phenotype exhibited in fibroblasts is crucial for promoting EMT. While EMT is not entirely reliant on its regulators like ZEB1/2, Twist, and Snail proteins, investigation of upstream signaling (like EGF, TGF-ß, Wnt) is required to get a more thorough understanding of tumor EMT. Throughout numerous cancers, connections between tumor epithelial and fibroblast cells that influence tumor growth have been found. The significance of cellular crosstalk stems from the fact that these events affect therapeutic response and disease prognosis. This study examines how classical EMT signals emanating from various cancer cells interfere to tumor metastasis, treatment resistance, and tumor recurrence.

Effects of kisspeptin on the maturation of human ovarian primordial follicles in vitro.

At this time, with advances in medical science, many cancers and chronic diseases are treatable, but one of their side effects is infertility. Some women also want to delay pregnancy for personal reasons. There has been some evidence that kisspeptin activates broad signals by binding to its receptor, suggesting that the role of kisspeptin in direct control of ovarian function includes follicle growth and steroid production. In this study, the effect of kisspeptin on improving the quality and results for human ovarian follicles was investigated. A section of ovary was removed laparoscopically from women between 20 and 35 years of age (n = 12). Pieces were divided randomly into two groups, control and treatment (with 1 µM kisspeptin). Real-time PCR was performed for GDF9, BMP15 and mTOR gene expression assessments. Western blotting was carried out to measure AKT and FOXO3a protein expression. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test; means were considered significantly different at a P-value < 0.05. During treatment with the kisspeptin group, maturity genes are expressed. Therefore, kisspeptin is an effective substance to improve the quality of the human ovarian medium as it increases the maturity of follicles.

Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers.

Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.

Nano-scale delivery systems for siRNA delivery in cancer therapy: New era of gene therapy empowered by nanotechnology.

RNA interference (RNAi) is a unique treatment approach used to decrease a disease's excessive gene expression, including cancer. SiRNAs may find and destroy homologous mRNA sequences within the cell thanks to RNAi processes. However, difficulties such poor cellular uptake, off-target effects, and susceptibility to destruction by serum nucleases in the bloodstream restrict the therapeutic potential of siRNAs. Since some years ago, siRNA-based therapies have been in the process of being translated into the clinic. Therefore, the primary emphasis of this work is on sophisticated nanocarriers that aid in the transport of siRNA payloads, their administration in combination with anticancer medications, and their use in the treatment of cancer. The research looks into molecular manifestations, difficulties with siRNA transport, the design and development of siRNA-based delivery methods, and the benefits and drawbacks of various nanocarriers. The trapping of siRNA in endosomes is a challenge for the majority of delivery methods, which affects the therapeutic effectiveness. Numerous techniques for siRNA release, including as pH-responsive release, membrane fusion, the proton sponge effect, and photochemical disruption, have been studied to overcome this problem. The present state of siRNA treatments in clinical trials is also looked at in order to give a thorough and systematic evaluation of siRNA-based medicines for efficient cancer therapy.

The effect of kisspeptin on the maturation of human ovarian follicles in culture following vitrification-thawing processes.

OBJECTIVE: Ovarian cryopreservation is one of the effective methods to preserve fertility for cancer patients. Still, this approach has some problems, namely ROS, resulting in adverse effects on oocytes and ovarian follicles. Kisspeptin as an antioxidant to control ovarian function, directly or indirectly. In this study, the effect of kisspeptin on follicle maturation was evaluated in culture following ovarian cryopreservation. METHODS: Ovarian tissue samples of women between 20 and 35 years old (n=12) were laparoscopically collected. The samples were randomly divided into four groups: 1) control, 2) vitrification, 3) vitrified+1µM kisspeptin, and 4) vitrified+10µM kisspeptin. After vitrification and thawing processes, the tissues were cultured in DMEM medium for 7 days. H&E staining for histological evaluation, Real-Time PCR for GDF9 and BMP15 gene expression, and immunohistochemical staining for GDF9 and BMP15 protein expression were performed. RESULTS: In the vitrification group, ovarian tissue morphology was incoherent, and more primordial follicles than other follicle types were found. The expression of GDF9 and BMP15 genes and proteins were significantly decreased in this group compared with other groups (p<0.05). In the vitrification groups with kisspeptin (1 and 10 µM), the number of primary and secondary follicles was more than in the vitrification group. Besides, the expression of these genes and proteins was dramatically elevated in the vitrification groups with kisspeptin compared to the vitrification group alone (p<0.05). CONCLUSIONS: It seems that kisspeptin is an effective substance to improve the quality of the human ovarian cryopreservation medium by improving follicle maturation.

The endocannabinoid system, a new gatekeeper in the pharmacology of human hepatocellular carcinoma.

Despite numerous prevention methodologies and treatment options, hepatocellular carcinoma (HCC) still remains as the third leading life-threatening cancer. It is thus pertinent to develop new treatment modality to fight this devastating carcinoma. Ample recent studies have shown the anti-inflammatory and antitumor roles of the endocannabinoid system in various forms of cancers. Preclinical studies have also confirmed that cannabinoid therapy can be an optimal regimen for cancer treatments. The endocannabinoid system is involved in many cancer-related processes, including induction of endoplasmic reticulum (ER) stress-dependent apoptosis, autophagy, PITRK and ERK signaling pathways, cell invasion, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) phenotypes. Moreover, changes in signaling transduction of the endocannabinoid system can be a potential diagnostic and prognostic biomarker for HCC. Due to its pivotal role in lipid metabolism, the endocannabinoid system affects metabolic reprogramming as well as lipid content of exosomes. In addition, due to the importance of non-coding RNAs (ncRNAs), several studies have examined the relationship between microRNAs and the endocannabinoid system in HCC. However, HCC is a pathological condition with high heterogeneity, and therefore using the endocannabinoid system for treatment has faced many controversies. While some studies favored a role of the endocannabinoid system in carcinogenesis and tumor induction, others exhibited the anticancer potential of endocannabinoids in HCC. In this review, specific studies delineating the relationship between endocannabinoids and HCC are examined. Based on collected findings, detailed studies of the molecular mechanism of endocannabinoids as well as preclinical studies for investigating therapeutic or carcinogenic impacts in HCC cancer are strongly suggested.

Receptor tyrosine kinase inhibitors in cancer.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.

Human umbilical cord mesenchymal stem cells: Heralding an effective treatment against esophageal cancer?

Esophageal cancer (EC), as one of the leading causes of cancer-associated mortality, influences a remarkable population of subjects globally and is histologically divided into two types, comprising esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Although several therapeutic approaches are present for EC, such as radiotherapy, chemotherapy, and surgery, these options have low success with serious side effects, for example, gastrointestinal toxicity, esophagitis, and pulmonary complications. Thus, utilizing an effective tool with low side effects is urgent. Newly, mesenchymal stem cells (MSCs) have received special interest for treating diverse diseases, such as cancer. Among different sources of MSCs, human umbilical cord MSCs have notable benefits, and reports expressed that they may be effective in EC treatment. For this purpose, in this review study, we aimed to summarize evidence regarding the effects of human umbilical cord MSCs on EC with a mechanistic insight.

Cancer stem cells in colorectal cancer: Signaling pathways involved in stemness and therapy resistance.

Colorectal cancer (CRC) is the third cause of cancer death worldwide. Although, in some cases, treatment can increase patient survival and reduce cancer recurrence, in many cases, tumors can develop resistance to therapy leading to recurrence. One of the main reasons for recurrence and therapy resistance is the presence of cancer stem cells (CSCs). CSCs possess a self-renewal ability, and their stemness properties lead to the avoidance of apoptosis, and allow a new clone of cancer cells to emerge. Numerous investigations inidicated the involvment of cellular signaling pathways in embryonic development, and growth, repair, and maintenance of tissue homeostasis, also participate in the generation and maintenance of stemness in colorectal CSCs. This review discusses the role of Wnt, NF-κB, PI3K/AKT/mTOR, Sonic hedgehog, and Notch signaling pathways in colorectal CSCs, and the possible modulating drugs that could be used in treatment for resistant CRC.

Tumor-derived exosomal non-coding RNAs as diagnostic biomarkers in cancer.

Almost all clinical oncologists agree that the discovery of reliable, accessible, and non-invasive biomarkers is necessary to decrease cancer mortality. It is possible to employ reliable biomarkers to diagnose cancer in the early stages, predict the patient prognosis, follow up the response to treatment, and estimate the risk of disease recurrence with high sensitivity and specificity. Extracellular vesicles (EVs), especially exosomes, have been the focus of translational research to develop such biomarkers over the past decade. The abundance and distribution of exosomes in bodily fluids, including serum, saliva, and urine, as well as their ability to transport various biomolecules (nucleic acids, proteins, and lipids) derived from their parent cells, make exosomes reliable, accessible, and potent biomarkers for diagnosis and follow-up of solid and hematopoietic tumors. In addition, exosomes play a vital role in various cellular processes, including tumor progression, by participating in intercellular communication. Although these advantages underline the high potential of tumor-derived exosomes as diagnostic biomarkers, the lack of standardized effective methods for their isolation, identification, and precise characterization makes their application challenging in clinical settings. We discuss the importance of non-coding RNAs (ncRNAs) in cellular processes, and the role of tumor-derived exosomes containing ncRNAs as potential biomarkers in several types of cancer. In addition, the advantages and challenges of these studies for translation into clinical applications are covered.

Umbilical cord mesenchymal stem cells and breast cancer: a good therapeutic candidate or not? A minireview.

Breast cancer (BC), as the most common cancer among women, affects a great number of subjects around the world. This heterogenic disease is divided into several types and subtypes, and each subtype has various phenotypes and genotypes. Against BC, several options have been proposed, such as surgery, radiotherapy, and chemotherapeutic agents. However, these approaches may have detrimental effects on health and life quality of patients. Hence, harnessing a therapeutic tool with high effectiveness and low side effects is required. Recently, mesenchymal stem cells (MSCs) have created a new window to treat various disorders, like cancer, and among these, umbilical cord (UC)-derived MSCs have acquired much interest due to their advantages. Therefore, in this narrative review, the influences of UC-derived MSCs on BC were reviewed and summarized with a focus on the molecular mechanisms involved in its pathogenesis and treatment.

Quercetin and Osteoarthritis: A Mechanistic Review on the Present Documents.

BACKGROUND: Osteoarthritis (OA), as one of the chronic debilitating conditions, affects 15% of people globally and is linked with serious problems, such as cardiovascular diseases, metabolic syndrome, and autoimmune inflammatory disorders. The current therapeutic options for this disease include nonsteroidal anti-inflammatory drugs, surgery, gene therapy, intrasynovial gel injection, and warm needle penetration. However, these approaches may be accompanied by considerable side effects, high costs, and some limitations for patients. Thus, using an alternative way is needed. SUMMARY: Presently, natural compounds based-therapies, like flavonoids, have acquired much attention in the current era. One of the compounds belonging to the flavonoid family is quercetin, and its therapeutic effects on disorders related to joints and cartilage have been addressed in vivo and in vitro studies. KEY MESSAGES: In this review, we summarized evidence indicating its curative capacity against OA with a mechanistic insight.

Can mesenchymal stem cells derived from adipose tissue and their conditioned medium improve ovarian functions? A mini-review.

Stable ovarian function is a key factor in the performance of the reproductive system. In contrast, some ovarian function-related diseases, such as polycystic ovarian syndrome, premature ovarian failure (POF), and ovarian cancer, are the main cause of infertility and death of women around the world. Despite multiple attempts, there are no effective tools against these conditions; however, mesenchymal stem cell-based therapy, especially using adipose tissue, has attracted much attention in medicine in light of its advantages such as easy isolation and accessibility. Conversely, it has been suggested that MSC-conditioned medium (CM) can restore injured tissues and has high immunocompatibility. So, here, we will summarize the effects of administration of MSCs and CM derived from adipose tissue on ovarian functions and related diseases.

Crosstalk between ferroptosis and the epithelial-mesenchymal transition: Implications for inflammation and cancer therapy.

Both genomic instability and the presence of chronic inflammation are involved in carcinogenesis and tumor progression. These alterations predispose the cancer cells to undergo metabolic reprogramming as well as the epithelial-mesenchymal transition (EMT). These pathways allow cancer cells to avoid apoptosis and stimulate tumor progression. EMT is an important early event in tumor cell invasion, which can be regulated through inflammatory signaling pathways. Cancer cells undergoing EMT are vulnerable to cell death by the process of ferroptosis. Ferroptosis is a form of regulated cell death involving iron-dependent lipid peroxidation, designed to maintain cellular homeostasis. Several reports have linked ferroptosis, inflammation, and cancer. Ferroptosis inhibitors and EMT inducers have been used to understand the anti-inflammatory and anticancer effects in experimental models. A better understanding of the crosstalk between ferroptosis and EMT, and the involvment of inflammatory mediators may accelerate the discovery of therapeutic strategies to eradicate cancer cells and overcome drug-resistance.

The Therapeutic Potential of Common Herbal and Nano-Based Herbal Formulations against Ovarian Cancer: New Insight into the Current Evidence.

Ovarian cancer (OCa) is characterized as one of the common reasons for cancer-associated death in women globally. This gynecological disorder is chiefly named the "silent killer" due to lacking an association between disease manifestations in the early stages and OCa. Because of the disease recurrence and resistance to common therapies, discovering an effective therapeutic way against the disease is a challenge. According to documents, some popular herbal formulations, such as curcumin, quercetin, and resveratrol, can serve as an anti-cancer agent through different mechanisms. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the contrary, using nano-based material, e.g., nanoparticles (NPs), micelles, liposomes, can significantly solve these limitations. Therefore, in the present study, we will summarize the anti-cancer aspects of these herbal and-nano-based herbal formulations with a focus on their mechanisms against OCa.