Inhibit Tumor Development Research Articles

WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway.

The proto-oncogene WWP1 is overexpressed in various cancers and contributes to tumor growth and poor prognosis. Recently, WWP1 inhibition was reported to suppress tumor development and cell proliferation by activating the PTEN function. However, the expression profiles and clinical significance of WWP1 in pancreatic ductal adenocarcinoma (PDAC) tissues remain undetermined. Therefore, this study aimed to evaluate the WWP1 expression in PDAC and investigate the therapeutic potential of WWP1 inhibition. Cellular proliferation assays were performed using a doxycycline-inducible shWWP1 expression system. Transcriptome analyses were conducted to identify the altered pathways in WWP1-depleted cells. PTEN ubiquitination by WWP1 was confirmed using immunoprecipitation assays. In vivo xenograft and drug screening assays were performed to evaluate the clinical significance of WWP1 inhibition. WWP1 was significantly upregulated in PDAC tissues and associated with poor prognosis. WWP1 depletion significantly reduced the proliferation of PDAC cell lines, correlating with the suppression of the PI3K-AKT pathway. Mechanistically, as reported in other cancer types, PTEN is a target of WWP1 in PDAC cells. PTEN silencing abrogated the growth-inhibitory effects in WWP1-depleted cells, suggesting that the anti-tumor effects of WWP1 inhibition are mediated through PTEN activation. In vivo xenograft studies confirmed that WWP1 depletion substantially inhibited tumor growth. Moreover, drug screening assays revealed that WWP1 depletion had an additive effect with the PI3K-AKT pathway inhibitors on hindering tumor growth. WWP1 inhibition enhances the anti-tumor effects of PI3K-AKT pathway inhibitors through PTEN activation. Thus, WWP1 could be a potential therapeutic target in PDAC.

PIWIL genes in hepatocellular carcinoma: a multi-omics approach uncovering dysregulated expression and ceRNA networks in mice

This multi-omics study delves into the expression patterns of PIWIL genes and their correlation with hepatocellular carcinoma (HCC) progression, utilizing whole transcriptome sequencing, bioinformatics, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) in mice. We identified differential expression levels of PIWIL genes between HCC and control tissues and analyzed their roles within the competing endogenous RNA (ceRNA) network related to regulatory non-coding RNA-mediated gene silencing (RNGS). Our findings showed that Piwil1 and Piwil4 were overexpressed while Piwil2 is underexpressed. As ceRNAs, specific lncRNAs, including Pvt1, Gas5, and BGIGI10090_38749, might sponge up miR-351-5p and miR-31-5p, promoting Piwil1 and Piwil4 expression, while miR-133b-3p, lacking ceRNA sponge absorption, continues to inhibit Piwil2. Through their interactions with PPI proteins encoded by RNGS genes, especially Dhx9, Drosha, Mov10, and Tdrd1, PIWI family members might play a multifaceted role in regulating gene expression and metabolic processes, thereby involving the development and progression of HCC. These interactions within the PPI network could influence the stability and activity of PIWIL proteins and contribute to the overall regulation of gene expression and HCC progression. In the RNGS, a diverse array of miRNAs, genes, lncRNAs, circRNAs, and pseudogenes have been observed, which are suggested to intricately interplay, potentially weaving a complex ceRNA regulatory network. Abnormally expressed miRNA-targeted genes in RNGS are associated with key biological processes, such as lipid metabolism and immune responses, crucial for tumor cell survival, and processes supporting tumor growth and invasion, like translation and cytoskeleton organization. This regulation is reflected in distinct KEGG pathways for downregulated and upregulated targets, highlighting the dualistic role of PIWIL genes in modulating HCC progression. The study concludes that PIWI family members have a correlation with HCC progression and play divergent roles in the pathogenesis, with overexpression of the Piwil1 and Piwil4 potentially promoting HCC progression and underexpression of Piwil2 likely suppressing tumor development. The ceRNA mechanism and PPI network are crucial in regulating the expression and function of PIWIL genes, respectively. The intricate ceRNA network potentially regulates the expression of miRNA-targeted genes in RNGS, which might be crucial for tumor survival and promotion, with impacts on immune responses and cell growth based on enriching results of dysregulated miRNA-targeted genes in HCC. By shedding light on the molecular intricacies of HCC, this multi-omics study underscores the pivotal roles of epigenetic regulations, especially the influence of PIWI family genes with other genes and ncRNAs in the RNGS process in HCC pathology. The findings offer valuable insights into the molecular mechanisms underpinning HCC, which may inform future research into potential targets for therapeutic intervention. The future research could benefit from integrating a diverse range of methodologies to further elucidate the roles of PIWIL genes in HCC progression, building upon the findings presented here.

Combination therapy of Lapatinib/Letrozole-based protein-vitamin nanoparticles to enhance the therapeutic effectiveness in drug-resistant breast cancer

HER2-positive breast cancer constitutes 20% of reported cases, characterized by excessive expression of HER2 receptors, pivotal in cell signaling and growth. Immunotherapy, the established treatment, often leads to multidrug resistance and tumor recurrence. There's a critical need for an effective strategy delaying drug resistance onset and ensuring cancer cell eradication. This study aimed to develop nanoparticles using human serum albumin (HSA) coupled with vitamin E (α-tocopherol succinate), loaded with a tyrosine kinase inhibitor (TKI) or aromatase inhibitor (AI). Nanoparticles were formed via desolvation, where HSA(VE) conjugates self-organized into a nanoparticle structure, incorporating TKI/AI either through chemical conjugation or direct binding to HSA. Physico-chemical analyses—such as infrared spectroscopy (IR), gel permeation chromatography (GPC), UV, IR, and CD spectroscopy confirmed HSA(VE) binding and drug incorporation into nanoparticles, evaluating their drug entrapment, release efficiency. Cell viability assays and in-vitro experiments on resistant and sensitive cell lines demonstrated effective drug encapsulation and absorption over time. Both in vitro and in vivo studies demonstrated that a combination of Lapa@HSA(VE) NPs and Let@HSA(VE) NPs in the ratio 75:25 inhibited tumor development and enhanced apoptosis significantly compared to individual NP treatment and free drug. The combination NPs therapy exhibited significant efficacy even in Lapa-resistant cell lines.

CD49a targeting enhances NK cell function and antitumor immunity.

Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance. Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models, and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a- tumor-infiltrating NK cells. Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using a monoclonal antibody suppressed tumor development in mice and combination treatment with anti-PD-L1 further enhanced antitumor efficacy. Our research reveals CD49a on NK cells as an immunotherapeutic target, and highlights the potential clinical applications of CD49a-targeted therapies.

β-carboline compound-10830733 suppresses the progression of non-small cell lung cancer by inhibiting the PI3K/Akt/GSK 3β signaling pathway

Lung cancer is one of the most commonly diagnosed cancers worldwide, with non-small cell lung cancer (NSCLC) accounting for 80–85% of cases. To clarify the mechanisms underlying its onset and development, and to identify small molecule compounds that target related pathways effectively inhibiting tumor development and transformation. Small molecular compounds with a β-carboline nucleus exhibit a range of biological activities, with significant anti-tumor effects. A series of small molecule β-carboline compounds were synthesized and the dominant structure 1- (3-chlorophenyl) - 9H -pyridino - [3,4-b] indole - 3 -carboxylic acid methyl ester (10830733) was initially screened out. However, the effect of 10830733 on NSCLC is unclear. In this study, we investigated the anti-NSCLC activity of 10830733 and explored its potential mechanisms of action. First, we found that 10830733 decreased proliferation and invasion and promoted apoptosis, as well as S and G2 phase cell cycle arrest in NSCLC cells. Furthermore, network pharmacological analysis and Western blot confirmed that 10830733 inhibits the PI3K/Akt/GSK 3β pathway, and that the PI3K inhibitor LY294002 enhances the effects of 10830733 on proliferation, invasion, apoptosis, S and G2 phase arrest, and the expression of PI3K/Akt/GSK 3β related proteins. In conclusion, our data demonstrate that 10830733 reduces proliferation and invasion, promotes S and G2 phase arrest and apoptotic cell death in NSCLC cells by suppressing the PI3K/Akt/GSK 3β signaling pathway, suggesting that 10830733 could be a promising new candidate for NSCLC therapy.

Mechanistic insights into traditional Chinese medicine for digestive tract cancers: implications for gastric, hepatic, esophageal, intestinal, and pancreatic tumors

Abstract The increasing incidence of cancer-related deaths highlights the pressing need for effective treatment modalities, particularly in the context of digestive tract cancers, such as gastric, hepatic, esophageal, intestinal, and pancreatic tumors. While conventional drug therapies play a critical role in managing these malignancies, their associated side effects often pose significant challenges to patient quality of life. Thus, there is a growing focus on traditional Chinese medicine (TCM) and its compounds, which are safe, non-toxic, and reliable. During anti-tumor therapy, TCM compounds, based on their multi-target, multi-pathway, and multi-level regulatory effects, fully mobilize multiple mechanisms of the body, presenting significant advantages in inhibiting tumor development, boosting patient welfare, and increasing their lifespan. This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell death, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM.

NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs protumor polarization. Our study explored the unique positive feedback loop between inflammasome and complement in TAMs. The present study identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed positive feedback with C1qA and drove TAMs protumor polarization via the LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed in TAMs and was associated with poorer prognosis in lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited TAMs protumor polarization. NLRP12-overexpressing TAMs promoted tumor cells’ malignant progression and inhibited T cells’ proliferation and cytotoxic function. Lastly, NLRP12 knockout (NLRP12−/−) reversed macrophage polarization, enhanced T-cell anti-tumor immunity, and suppressed tumor growth. Our findings highlighted the essential role of NLRP12/C1qA positive feedback loop and the LILRB4/NF-κB pathway in promoting TAMs protumor polarization. Inhibition of NLRP12 suppressed tumor development and promoted immune response. NLRP12 may be a promising target for LUAD immunotherapy.

Expression of myoglobin by tumor cells and its role in progression of malignancy

The review examines available literature data on the expression of myoglobin in various tumors and tumor cell lines of non-muscle nature, and the effect of hypoxia, reactive oxygen and nitrogen species, hormones, growth factors, gender and age on this process. The influence of tumor myoglobin on processes occurring in cells – oxidative stress, inhibition of mitochondrial respiration by nitric oxide and fatty acid metabolism is also analyzed, both in the case of intrinsic endogenous (ectopic) expression of small amounts (~1 µM) of myoglobin and overexpression of the protein (~150 µM) via the myoglobin gene embedded in the tumour cell genome. It is concluded that hypoxia-induced intrinsic expression of low concentrations of myoglobin, due to its ability to utilise reactive oxygen and nitrogen species that can damage tumour cells, ensures their better survival, promoting tumour progression and metastasis. Accordingly, this myoglobin expression is generally associated with a more aggressive tumour type and poor prognosis for the course and outcome of the disease, and may thus serve as a “marker” of an aggressive malignancy. In contrast, artificial overexpression of myoglobin can significantly inhibit tumour development and improve disease course by switching cancer cell metabolism from tumour-specific glycolysis to oxidative phosphorylation inherent in healthy tissue. Myoglobin overexpression may thus be an effective therapeutic tool in oncology.

L-Securinine Induces ROS-Dependent Apoptosis on Pancreatic Cancer Cells via the PI3K/AKT/mTOR Signaling Pathway.

Accumulating evidence has shown that l-securinine can, in certain circumstances, suppress tumor development by elevating reactive oxygen species (ROS) levels. The current work set out to examine l-securinine's apoptotic effects on HuP-T3 cells as well as any potential underlying molecular mechanism(s) that could explain its action as an anticancer agent. In this study, we used 1.2B4 cells as a control human cell line to verify our findings. Hup-T3 and 1.2B4 cells were cultured with a medium containing the following dilutions of l-securinine: 1-10 μΜ for up to 72 h. We examined the viability and proliferation levels of cells in both cell lines. Then, we measured only 1.2B4 insulin levels and content. We also quantified cell apoptosis, cell cycle levels, and the intracellular reactive oxygen species on HuP-T3 and 1.2B4. Afterwards, we performed a real-time quantitative polymerase chain reaction and western blot analysis. Our results demonstrated that l-securinine inhibited both proliferation and growth of Hup-T3 cells, showing inhibitory and antiproliferative activity in comparison with the control group. In addition, l-securinine had no impact on the proliferation and growth of 1.2B4 cells, nor on their insulin levels and content. By boosting ROS production, and inhibiting the PI3K/AKT/mTOR signaling pathway, l-securinine induced apoptosis on HuP-T3 cells. Pancreatic cancer was successfully inhibited by l-securinine in vitro. l-securinine triggers ROS-dependent apoptosis on pancreatic cancer cells while inhibiting the PI3K/AKT/mTOR signaling pathway. These findings suggest that l-securinine holds promise as a potential lead for future drug development in the fight against pancreatic adenocarcinoma.

Mitochondria in tumor immune surveillance and tumor therapies targeting mitochondria.

Mitochondria play a central role in cellular energy production and metabolic regulation, and their function has been identified as a key factor influencing tumor immune responses. This review provides a comprehensive overview of the latest advancements in understanding the role of mitochondria in tumor immune surveillance, covering both innate and adaptive immune responses. Specifically, it outlines how mitochondria influence the function of the tumor immune system, underscoring their crucial role in modulating immune cell behavior to either promote or inhibit tumor development and progression. Additionally, this review highlights emerging drug interventions targeting mitochondria, including novel small molecules with significant potential in cancer therapy. Through an in-depth analysis, it explores how these innovative strategies could improve the efficacy and outlook of tumor treatment.

Assessment <b></b>of Serum P53 Protein Level in Adult Patients with Acute Myeloid Leukemia in Correlation with Response to Treatment

Background: Acute myeloid leukemia (AML) is an adult leukemia characterized by rapid proliferation of undifferentiated myeloid precursors, leading to bone marrow (BM) failure and impaired erythropoiesis. The p53 tumor suppressor protein regulates cell division and inhibits tumor development by preventing cell proliferation of altered or damaged DNA. It orchestrates various cellular reactions, including cell cycle arrest, DNA repair, and antioxidant properties. Objectives: To investigate the relationship of P53 serum level with hematological findings, remission, and survival status in de novo AML patients. Methods: This is a cross-sectional study that enrolled 63 newly diagnosed de novo AML patients, and 15 sex- and age-matched healthy persons as a control group. Serum P53 levels were assessed using the enzyme-linked immunosorbent assay (ELISA) technique before initiating induction chemotherapy. The study was performed between November 2022 and May 2023 at the Hematology and Bone Marrow Transplant Center of the Medical City Complex in Baghdad. Results: There were significantly lower P53 serum levels in AML patients before starting chemotherapy compared to the control group. However, no substantial difference in P53 levels was identified between AML patients achieving complete remission and those exhibiting no response, nor between alive and deceased individuals. Furthermore, there was a positive yet statistically non-significant correlation between serum P53 levels and age, and no significant relationship between P53 levels and sex or various hematological parameters. Conclusion: P53 levels are low in AML patients. They are not associated with remission status or survival after six months and are not correlated with hematological values.

Alginate-functionalized and 4T1 cell membrane-coated multi-tasking nanoparticulate system for near-infrared-triggered photodynamic therapy on breast cancer: In vitro cellular and in vivo mice models

Recently, combination treatment of chemo-dynamic therapy (CDT) and photodynamic therapies (PDT) is well-known and prominent therapeutic strategy for breast tumor. Importantly, tailored nanomedicines with unique personalized properties including nanocarrier suitability and effective targeting ability that requires the exhaustive understanding of tumor microenvironment. Recently, researchers have designed a smart upconversion nanoparticles (UCNPs) that have unique characteristics to achieve targeting for respond tumor microenvironment. In the present study, we first time fabricated a novel combination of oxidized sodium alginate-enveloped and 4T1 cancer cell membrane-coated up-conversion nanoparticles (4TUCNP@SMZ) were engineered for breast cancer-targeted therapy. The nanoparticles could be formed via electrostatic interaction, which showed excellent biocompatibility, increased cellular uptake with normal and cancer cells. The fabricated Alginate and 4T1-membrane functionalized up-conversion nanoparticles significantly benefitted to targeted delivery system for local breast cancer and prominently inhibit tumor development via chemo-dynamic therapy (CDT) and PDT. The greater susceptibility of tumor cells to oxidative stress may also result from the depletion of intracellular GSH by the 4TUCNP@SMZ nanoparticles. The in vitro cell models (4T1 and MCF-7), in vivo tumor model and histological observation demonstrated that 4TUCNP@SMZ nanoparticles effectively targeted to breast tumor microenvironment and inhibit breast cancer cells. This report suggested that multifunctional Alginate-functionalized nanoparticles are a versatile agent for phototherapy for breast cancer treatment.

Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels

BAP1, BRCA1-Associated Protein 1, serves as a novel tumor suppressor through the deubiquitination of monoubiquitination of H2A and subsequent gene transcriptional regulation. Regulated cell death like apoptosis or ferroptosis is considered an essential mechanism mediating tumor suppression. Previous reports, including ours, have demonstrated that BAP1 could promote apoptosis and ferroptosis to inhibit tumor development. Whether BAP1 regulated additional types of cell death remains unclear. Disulfidptosis is a recently identified novel cell death mode characterized by aberrant accumulation of intracellular disulfide (e.g., cystine) and depletion of NADPH. In this study, we first demonstrated that BAP1 could significantly protect disulfidptosis induced by glucose starvation, which is validated by various cell death inhibitors and the accumulation of disulfide bonds in the cytoskeleton proteins. BAP1 is known to inhibit SLC7A11 expression. We found that the protective effect of BAP1 against disulfidptosis was counteracted when overexpressing SLC7A11 or adding additional cystine. Conversely, BAP1-mediated suppression of disulfidptosis was largely abrogated when SLC7A11-mediated cystine uptake was inhibited by the knockout of SLC7A11 or erastin treatment. Besides, high BAP1 expression showed lower NADP+/NADPH levels, which might confer resistance to disulfidptosis. Consistent with these observations, the expression level of BAP1 was also positively correlated with NADPH-related genes in KIRC patients, though the underlying mechanism mediating NADPH regulation remains further investigation. In summary, our results revealed the role of BAP1 in the regulation disulfidptosis and provided new insights into the understanding of disulfidptosis in tumor development.

Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression.

Cholangiocarcinoma (CCA) is a rare but highly invasive cancer, with its incidence rising in recent years. Currently, surgery remains the most definitive therapeutic option for CCA. However, similar to other malignancies, most CCA patients are not eligible for surgical intervention at the time of diagnosis. The chemotherapeutic regimen of gemcitabine combined with cisplatin is the standard treatment for advanced CCA, but its effectiveness is often hampered by therapeutic resistance. Recent research highlights the remarkable plasticity of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME). TAMs play a crucial dual role in either promoting or suppressing tumor development, depending on the factors that polarize them toward pro-tumorigenic or anti-tumorigenic phenotypes, as well as their interactions with cancer cells and other stromal components. In this review, we critically examine recent studies on TAMs in CCA, detailing the expression patterns and prognostic significance of different TAM subtypes in CCA, the mechanisms by which TAMs influence CCA progression and immune evasion, and the potential for reprogramming TAMs to enhance anticancer therapies. This review aims to provide a framework for deeper future research.

The natural compound periplogenin suppresses the growth of prostate carcinoma cells by directly targeting ATP1A1

Natural compounds constitute a major resource for the development of medicines for multiple diseases. While many natural compounds show strong biological activity, the mechanisms that confer clinical benefits are often elusive and have been attributed to multiple pathways. Periplogenin (PPG), a natural compound isolated from Cortex periplocae, exhibits strong anti-tumor activities in several human cancer cell lines. However, its molecular mode of action remained unclear. In this study, we leveraged a forward genetic screening approach in DU145 prostate cancer cells to uncover the molecular target of PPG using chemical mutagenesis. Next generation sequencing revealed that a single amino acid substitution at amino acid 804 in ATP1A1 (ATPase Na + /K + Transporting Subunit Alpha 1) confers resistance to the cytotoxic activity of PPG. Mechanistically, ATP1A1 T804 forms a hydrogen bond with PPG which is abolished by the T804A substitution in ATP1A1, resulting in resistance to PPG treatment in vitro. Importantly, in vivo, PPG strongly suppressed tumor development in a DU145 xenograft model whereas DU145 xenograft tumors carrying a ATP1A1-T804A mutation were largely unaffected by the treatment. These findings demonstrate that PPG suppresses the growth of DU145 prostate cancer cells in vitro and in vivo by directly binding to ATP1A1 and highlight the power of our unbiased forward genetic screening approach to uncover direct drug target structures at single amino acid resolution.

Overcoming cisplatin resistance in ovarian cancer: A novel approach via mitochondrial targeting peptide Pal-pHK-pKV

Cisplatin (DDP) resistance in advanced stages of ovarian cancer significantly reduces survival rates. Mitochondria may serve as a potential therapeutic target for ovarian cancer. Pal-pHK-pKV is a mitochondrial targeting peptide synthesized by supramolecular assembly. Our study aims to investigate whether Pal-pHK-pKV serves as a useful strategy to reverse DDP resistance in ovarian cancer. Subcutaneous tumor implantation of the DDP-resistant ovarian cancer cell line A2780CP was conducted in nude mice, and drugs were administered intraperitoneally to compare the inhibitory effects of Pal-pHK-pKV and DDP on A2780CP cells in vivo. Combination index values were calculated for various concentrations of DDP and Pal-pHK-pKV to determine the optimal combination concentration. Mitochondrial membrane potential, cytochrome C distribution and immunofluorescence were also measured. Our studies demonstrated that Pal-pHK-pKV treatment reduced the proliferation, invasion and metastasis of ovarian cancer cells and impaired mitochondrial function. Furthermore, the combination of Pal-pHK-pKV and DDP exhibited a synergistic effect. Mechanistically, Pal-pHK-pKV can impair mitochondrial function, reduce mitochondrial membrane potential and release ROS. On the other hand, Pal-pHK-pKV can affect ERK pathway activation and inhibit tumor development. In conclusion, the mitochondria-specific amphiphilic peptide Pal-pHK-pKV provides a novel approach for treating ovarian cancer and may potentially overcome DDP drug resistance.

Neoplastic ICAM-1 protects lung carcinoma from apoptosis through ligation of fibrinogen

Intercellular cell adhesion molecule-1 (ICAM-1) is frequently overexpressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the mechanism underlying the negative effects of neoplastic ICAM-1 remains obscure. Herein, we demonstrate that the survival of NSCLC cells but not normal human bronchial epithelial cells requires an anti-apoptosis signal triggered by fibrinogen γ chain (FGG)–ICAM-1 interaction. ICAM-1–FGG ligation preserves the tyrosine phosphorylation of ICAM-1 cytoplasmic domain and its association with SHP-2, and subsequently promotes Akt and ERK1/2 activation but suppresses JNK and p38 activation. Abolishing ICAM-1–FGG interaction induces NSCLC cell death by activating caspase-9/3 and significantly inhibits tumor development in a mouse xenograft model. Finally, we developed a monoclonal antibody against ICAM-1–FGG binding motif, which blocks ICAM-1‒FGG interaction and effectively suppresses NSCLC cell survival in vitro and tumor growth in vivo. Thus, suppressing ICAM-1–FGG axis provides a potential strategy for NSCLC targeted therapy.

Tumour growth inhibitory effect of Ibervillea sonorae phytopreparations in cervical cancer xenografts

Cucurbitacin IIb, a triterpene obtained from the Ibervillea sonorae plant, reduces tumour development in a preclinical model of cervical cancer. Acetison and Etanison, phytopreparations made from I. sonorae, present biological activity analogous to CIIb in HeLa. This research evaluated the tumour growth inhibitory effect of these phytopreparations in a HeLa xenograft tumour model in BALB/c nude mice. Tumours in mice were treated every 3 days for 12 days with cisplatin (2 mg/kg), CIIb (5 mg/kg), Acetison (20 mg/kg), Etanison (30 mg/kg), and DMSO at 2%. For histological observations, tumours were stained with H&E. Fingerprinting of both phytopreparations was performed using HPLC-UV and UHPLC-APCI-IT-MS. Both phytopreparations and CIIb inhibit tumour development as well as Cisplatin (75.5%); Etanison (77.7%), Acetison (73.6%), and CIIb (73.0%). Furthermore, only tumours treated with cisplatin showed invasion of bone tissue. The results show the potential use of I. sonorae phytopreparations in the treatment of cervical cancer.

Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development.

Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11chi DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11chi DCs. Constitutive loss of CD11chi DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11chi DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11chi DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors.

CLINICAL APPLICATIONS OF STEM CELL THERAPY IN THE FIGHT AGAINST CANCER

Stem cell therapy is emerging as a novel approach in the fight against cancer, with over 300 clinical trials exploring various stem cell types, including embryonic, adult, fetal, amniotic fluid, and human embryonic-like stem cells. These trials aim to treat a range of diseases, notably cancer, by leveraging the regenerative capabilities of stem cells. Cancer stem cells (CSCs), a subpopulation within tumors, are integral to tumor growth and resistance to conventional treatments due to their self-renewal properties. Innovative strategies, such as suicide gene therapy using genes like Cytosine Deaminase (CD), show promise in targeting these CSCs and enhancing treatment outcomes. This review discusses the dual role of stem cells in cancer therapy, highlighting their potential to both promote and inhibit tumor development, and underscores the need for well-characterized therapeutic stem cell banks equipped with anti-tumor genes. Future research directions and the potential of stem cell-based therapies to revolutionize cancer treatment are also explored.