Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Edible bird's nest improves hemorheology and immune function in mice with transplanted uterine leiomyomas.

OBJECTIVE: To investigate the effect of edible bird's nest (EBN) on tumor growth, hemorheology and immune function of mice with transplanted uterine myomas. METHODS: A subcutaneous tumor model of human uterus myoma was established in mice, and the mice were randomly divided into a model group, EBN group, estradiol receptor (ER) group and ER+EBN group. Body weight and tumor volume were measured at 2 weeks, 4 weeks and 8 weeks after the uterus myoma transplantation. Eight weeks after transplantation, the tumor weight was assessed, the morphology of different organs was observed, and the pathological changes of the uterus myoma was observed. Besides, the levels of ER and progesterone receptor (PR), various hemorheological parameters (including hematocrit, plasma viscosity and whole blood viscosity under different shearing conditions), and immune functions (CD3 +, CD4 + and CD8 + cells) were also measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), nitricoxidesynthase (NOS) and vascular endothelial growth factor (VEGF) in each group. RESULTS: There were no statistical differences in body weight, tumor weight, tumor volume, uterus myoma pathology or the levels of ER and PR between the model group and EBN group, nor between the ER group and ER+EBN group (all P>0.05). Similarly, no notable morphological differences were observed in the heart, liver, spleen, lung, kidney, stomach, intestines and uterus among different groups (all P>0.05). However, in contrast to the model group, the EBN group exhibited significant reductions in hemorheology indicators, the proportion of CD8 + cells, as well as the levels of TNF-α, NOS and VEGF (all P<0.05). Conversely, the proportion of CD3 + and CD4 + cells, the CD4 +/CD8 + ratio and the level of IL-2 in the EBN group were obviously increased (all P<0.05). Compared with the ER group, the proportion of CD8 + cells, the levels of TNF-α, NOS and VEGF in the ER+EBN group were significantly decreased while the proportion of CD3 + and CD4 + cells, the CD4 +/CD8 + ratio and the level of IL-2 in the ER+EBN group were obviously increased. CONCLUSION: For mice with uterine myoma transplantation, EBN does not influence tumor growth but significantly regulates hemorheology and enhances immune function.

Tumor Growth Pattern and Intra- and Peritumoral Radiomics Combined for Prediction of Initial TACE Outcome in Patients with Primary Hepatocellular Carcinoma.

Purpose: Non-invasive methods are urgently needed to assess the efficacy of transarterial chemoembolization (TACE) and to identify patients with hepatocellular carcinoma (HCC) who may benefit from this procedure. This study, therefore, aimed to investigate the predictive ability of tumor growth patterns and radiomics features from contrast-enhanced magnetic resonance imaging (CE-MRI) in predicting tumor response to TACE among patients with HCC. Patients and Methods: A retrospective study was conducted on 133 patients with HCC who underwent TACE at three centers between January 2015 and April 2023. Enrolled patients were divided into training, testing, and validation cohorts. Rim arterial phase hyperenhancement (Rim APHE), tumor growth patterns, nonperipheral washout, markedly low apparent diffusion coefficient (ADC) value, intratumoral arteries, and clinical baseline features were documented for all patients. Radiomics features were extracted from the intratumoral and peritumoral regions across the three phases of CE-MRI. Seven prediction models were developed, and their performances were evaluated using receiver operating characteristic (ROC) and decision curve analysis (DCA). Results: Tumor growth patterns and albumin-bilirubin (ALBI) score were significantly correlated with tumor response. Tumor growth patterns also showed a positive correlation with tumor burden (r = 0.634, P = 0.000). The Peritumor (AUC = 0.85, 0.71, and 0.77), Clinics_Peritumor (AUC = 0.86, 0.77, and 0.81), and Tumor_Peritumor (AUC = 0.87, 0.77, and 0.80) models significantly outperformed the Clinics and Tumor models (P < 0.05), while the Clinics_Tumor_Peritumor model (AUC = 0.88, 0.81, and 0.81) outperformed the Clinics (AUC = 0.67, 0.77, and 0.75), Tumor (AUC = 0.78, 0.72, and 0.68), and Clinics_Tumor (AUC = 0.82, 0.83, and 0.78) models (P < 0.05 or 0.053, respectively). The DCA curve demonstrated better predictive performance within a specific threshold probability range for Clinics_Tumor_Peritumor. Conclusion: Combining tumor growth patterns, intra- and peri-tumoral radiomics features, and ALBI score could be a robust tool for non-invasive and personalized prediction of treatment response to TACE in patients with HCC.

Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice.

This study evaluates the efficacy of [131I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [131I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [131I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [131I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity.

Acetate-producing bacterium Paenibacillus odorifer hampers lung cancer growth in lower respiratory tract: an in vitro study.

Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

Harnessing Flex Point Symmetry to Estimate Logistic Tumor Population Growth.

The observed time evolution of a population is well approximated by a logistic growth function in many research fields, including oncology, ecology, chemistry, demography, economy, linguistics, and artificial neural networks. Initial growth is exponential, then decelerates as the population approaches its limit size, i.e., the carrying capacity. In mathematical oncology, the tumor carrying capacity has been postulated to be dynamically evolving as the tumor overcomes several evolutionary bottlenecks and, thus, to be patient specific. As the relative tumor-over-carrying capacity ratio may be predictive and prognostic for tumor growth and treatment response dynamics, it is paramount to estimate it from limited clinical data. We show that exploiting the logistic function's rotation symmetry can help estimate the population's growth rate and carry capacity from fewer data points than conventional regression approaches. We test this novel approach against published pan-cancer animal and human breast cancer data, achieving a 30% to 40% reduction in the time at which subsequent data collection is necessary to estimate the logistic growth rate and carrying capacity correctly. These results could improve tumor dynamics forecasting and augment the clinical decision-making process.

PULSAR Effect: Revealing potential synergies in combined radiation therapy and immunotherapy via differential equations.

PULSAR (personalized ultrafractionated stereotactic adaptive radiotherapy) is a form of radiotherapy method where a patient is given a large dose or "pulse" of radiation a couple of weeks apart rather than daily small doses. The tumor response is then monitored to determine when the subsequent pulse should be given. Pre-clinical trials have shown better tumor response in mice that received immunotherapy along with pulses spaced 10 days apart. However, this was not the case when the pulses were 1 or 4 days apart. Therefore, a synergistic effect between immunotherapy and PULSAR is observed when the pulses are spaced out by a certain number of days. In our study, we aimed to develop a mathematical model that can capture the synergistic effect by considering a time-dependent weight function that takes into account the spacing between pulses. We determined feasible parameters by fitting murine tumor volume data of six treatment groups via simulated annealing algorithm. Applying these parameters to the model we simulated 4000 trials with varying sequencing of pulses. These simulations indicated that if pulses were spaced apart by at least 9 days the tumor volume was about 200 mm3 to 250 mm3 smaller when treated with PULSAR combined with immunotherapy. We successfully demonstrate that our model is simple to implement and can generate tumor volume data that is consistent with the pre-clinical trial data. Our model has the potential to aid in the development of clinical trials of PULSAR therapy.

RNA methyltransferase NSUN2-mediated m5C methylation promotes Cr(VI)-induced malignant transformation and lung cancer by accelerating metabolism reprogramming.

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyltransferase NSUN2 was significantly upregulated in Cr(VI)-transformed cells and lung tissues of Cr(VI)-exposed mice. Inhibition of NSUN2 reduced cell proliferation, migration, colony formation and tube formation abilities. We found NSUN2-mediated m5C modification induced metabolic reprogramming and cell cycle by promoting the mRNA stabilities of ME1, GLUT3 and CDK2. In addition, knockdown of NSUN2 attenuated tumorigenesis and angiogenesis in vivo. RNA m5C reader ALYREF was identified to be involved in NSUN2-mediated m5C modification in Cr (VI)-induced carcinogenesis. Further study showed that EP300 induced NSUN2 upregulation through transcriptional activation by inducing histone modification at H3K27ac site for regulating Cr(VI) carcinogenesis. Our findings demonstrated novel role and mechanism of NSUN2 and epigenetic changes by increasing the RNA m5C modification that are important for Cr (VI)-induced carcinogenesis through NSUN2/ALYREF pathway. NSUN2, ALYREF, ME1, GLUT3 or/and CDK2 may be used as potential new biomarkers or/and therapeutic target(s) in the future.

Exploring the Impact of Exercise-Derived Extracellular Vesicles in Cancer Biology.

Cancer remains a major challenge in medicine, prompting exploration of innovative therapies. Recent studies suggest that exercise-derived extracellular vesicles (EVs) may offer potential anti-cancer benefits. These small, membrane-bound particles, including exosomes, carry bioactive molecules such as proteins and RNA that mediate intercellular communication. Exercise has been shown to increase EV secretion, influencing physiological processes like tissue repair, inflammation, and metabolism. Notably, preclinical studies have demonstrated that exercise-derived EVs can inhibit tumor growth, reduce metastasis, and enhance treatment response. For instance, in a study using animal models, exercise-derived EVs were shown to suppress tumor proliferation in breast and colon cancers. Another study reported that these EVs reduced metastatic potential by decreasing the migration and invasion of cancer cells. Additionally, exercise-induced EVs have been found to enhance the effectiveness of chemotherapy by sensitizing tumor cells to treatment. This review highlights the emerging role of exercise-derived circulating biomolecules, particularly EVs, in cancer biology. It discusses the mechanisms through which EVs impact cancer progression, the challenges in translating preclinical findings to clinical practice, and future research directions. Although research in this area is still limited, current findings suggest that EVs could play a crucial role in spreading molecules that promote better health in cancer patients. Understanding these EV profiles could lead to future therapies, such as exercise mimetics or targeted drugs, to treat cancer.

The crossroad between tumor and endothelial cells.

Endothelial cells are critical in tumor development, and the specific targeting of endothelial cells offers a potent means to effectively impede angiogenesis and suppress the growth of tumors. Tumor endothelial cells are responsible for the loss of anticancer immunity, the so-called endothelial anergy, i.e., the unresponsiveness of tumor endothelial cells to pro-inflammatory stimulation, not allowing adhesion of immune cells to the endothelium. Endothelial cells downregulate antigen presentation and recruitment of immune cells, contributing to immunosuppression. Targeting endothelial cells may assist in improving the immune effect of immune cells in tumor microenvironment.

Survival benefit of sequential curative treatment for TACE suitable BCLC stage B HCC patients.

To clarify the survival benefit of sequential curative treatment post transcatheter arterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), we retrospectively analyzed HCC patients at a hospital. From July 2017 to July 2020, 787 treatment-naïve HCC patients underwent initial treatment; 77 (9.8%) meeting inclusion criteria were enrolled. Their initial treatments were TACE only (n = 68, 88.3%) or TACE with other treatments (n = 9, 11.7%). Median survival of the TACE-only group was 30 months. Treatment response was evaluated after 2 or 3 consecutive TACEs for patients (54/68, 79.4%) with available pre-/post-TACE computerized tomography (CT) or magnetic resonance imaging (MRI). Treatment responses was divided into 4 groups: complete (n = 14, 26%, group (Gr) 1), incomplete without new tumor growth (n = 28, 52.0%, Gr2), incomplete with new growth (n = 6, 11%, Gr3), and progression (n = 6, 11%, Gr4). Of Gr2, further treatment after TACE were had radiofrequency ablation (n = 13, Gr2a), TACE (n = 9, Gr2b), other modalities (n = 6, Gr2c. Gr2a's median survival was longer than Gr2b's (> 60 vs. 20 months, p = 0.007). Nine patients in Gr2a (69%, 9/13) achieved a complete response, but none in Gr2b (p = 0.001). Conclusively, in TACE-suitable BCLC stage B HCC patients, a partial response without new tumor growth can serve as an indicator of treatment effectiveness following initial TACE treatment. This can facilitate the selection of appropriate candidates to receive RFA, potentially resulting in improved patient survival.

The up-regulation of SYNCRIP promotes the proliferation and tumorigenesis via DNMT3A/p16 in colorectal cancer.

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a group of proteins that control gene expression, have been implicated in many post-transcriptional processes. SYNCRIP (also known as hnRNP Q), a subtype of hnRNPs, has been reported to be involved in mRNA splicing and translation. In addition, the deregulation of SYNCRIP was found in colorectal cancer (CRC). However, the role of SYNCRIP in regulating CRC growth remains largely unknown. Here, we found that SYNCRIP was highly expressed in colorectal cancer by analyzing TCGA and GEPIA database. Furthermore, we confirmed the expression of SYNCRIP expression in CRC tumor and CRC cell lines. Functionally, SYNCRIP depletion using shRNA in CRC cell lines (SW480 and HCT 116) resulted in increased caspase3/7 activity and decreased cell proliferation, as well as migration. Meanwhile, overexpression of SYNCRIP showed opposite results. Mechanistically, SYNCRIP regulated the expression of DNA methyltransferases (DNMT) 3A, but not DNMT1 or DNMT3B, which affected the expression of tumor suppressor, p16. More importantly, our in vivo experiments showed that SYNCRIP depletion significantly inhibited colorectal tumor growth. Taken all together, our results suggest SYNCRIP as a potent therapeutic target in colorectal cancer.

Transcriptional Regulation of De Novo Lipogenesis by SIX1 in Liver Cancer Cells.

De novo lipogenesis (DNL), a hallmark of cancer, facilitates tumor growth and metastasis. Therapeutic drugs targeting DNL are being developed. However, how DNL is directly regulated in cancer remains largely unknown. Here, transcription factor sine oculis homeobox 1 (SIX1) is shown to directly increase the expression of DNL-related genes, including ATP citrate lyase (ACLY), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1), via histone acetyltransferases amplified in breast cancer 1 (AIB1) and lysine acetyltransferase 7 （HBO1/KAT7）, thus promoting lipogenesis. SIX1 expression is regulated by insulin/lncRNA DGUOK-AS1/microRNA-145-5p axis, which also modulates DNL-related gene expression as well as DNL. The DGUOK-AS1/microRNA-145-5p/SIX1 axis regulates liver cancer cell proliferation, invasion, and metastasis in vitro and in vivo. In patients with liver cancer, SIX1 expression is positively correlated with DGUOK-AS1 and SCD1 expression and is negatively correlated with microRNA-145-5p expression. DGUOK-AS1 is a good predictor of prognosis. Thus, the DGUOK-AS1/microRNA-145-5p/SIX1 axis strongly links DNL to tumor growth and metastasis and may become an avenue for liver cancer therapeutic intervention.

CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition.

EGFR-TKIs have been used as frontline treatment in patients with advanced non-small cell lung cancer (NSCLC) suffering from the EGFR mutation. Gefitinib, the first-generation EGFR-TKI, has greatly improved survival rates in lung cancer patients, whereas acquired gefitinib resistance is still a critical issue that needs to be overcome. In our research, high expression levels of CIB2 were found in gefitinib-resistant lung cancer cells. CIB2 knockout rendered gefitinib-resistant cells more sensitive to gefitinib, and overexpression of CIB2 in parental cells was sufficient to induce more resistance to gefitinib. Inhibition of CIB2 in gefitinib-resistant lung cancer cells significantly induced cell apoptosis. To clarify the major molecular mechanism by which CIB2 increases gefitinib resistance, we demonstrated that raised CIB2 in lung cancer cells promoted epithelial-to-mesenchymal transition (EMT) through upregulation of ZEB1. Moreover, FOSL1 transcriptionally regulated CIB2 expression. Finally, CIB2 rendered tumors resistant to gefitinib treatment in vivo. Our results explored a new mechanism: upregulated CIB2 promoted EMT through ZEB1 to regulate gefitinib resistance, which could be a candidate therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.

Dendrobine Suppresses Tumor Growth by Regulating the PD-1/PD-L1 Checkpoint Pathway in Lung Cancer.

BACKGROUND: Dendrobine is a bioactive alkaloid isolated from Dendrobium nobile. Studies have evaluated the anti-tumor effect of dendrobine in cancers, including lung cancer. However, the mechanism of dendrobine inhibiting tumors requires further study. METHODS: Bioinformatics was performed to screen the potential targets of dendrobine. The in-tersection of dendrobine and lung cancer targets was performed for KEGG analysis. CCK-8 was used to detect cell viability after dendrobine treatment. A xenograft mouse model was es-tablished to explore the effect of dendrobine on lung cancer. The percentages of PD-L1+, CD4+, CD8+, CD11b+, CD25+FOXP3+ cells, the expression of Ki-67 and caspase-3, the ex-pression of pathway-related proteins, the levels of IL-2, IFN-γ, and TGF-ß, and the changes of indicators of liver and renal function were measured. RESULTS: Dendrobine regulated the PD1/PD-L1 checkpoint signaling pathway and affected the occurrence and development of lung cancer. Dendrobine decreased the cell viability of lung cancer. Dendrobine and anti-PD-L1 decreased tumor growth, increased caspase-3 expression, and reduced Ki-67 expression in tumor tissues. Dendrobine and anti-PD-L1 suppressed pro-tein expression of PD-L1, p-JAK1/JAK1, and p-JAK2/JAK2 in tumor tissues. Greatly, den-drobine and anti-PD-L1 decreased the percentages of PD-L1+, CD11b+, and CD25+FOXP3+ cells, increased the percentages of CD4+ and CD8+cells, and enhanced the levels of IL-2, IFN-γ, and TGF-ß in tumor tissues. Dendrobine demonstrated no hepatorenal toxicity to the tumor mice. The combination of dendrobine and anti-PD-L1 greatly strengthened the effects of dendrobine on tumors. CONCLUSION: Dendrobine inhibited tumor immune escape by suppressing the PD-1/PD-L1 checkpoint pathway, thus restricting tumor growth of lung cancer.

Prognostic Impact of Tumor Growth Rate During Second-line Chemotherapy in Patients With Gastric Cancer.

Background/Aim: Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. Patients and Methods: We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. Results: The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Conclusion: Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR.

CXCL10 promotes melanoma angiogenesis and tumor growth.

Upregulation of CXC motif chemokine 10 (CXCL10) in melanoma patients has been found to be associated with melanoma progression. However, the role of endogenous CXCL10 from the host in melanoma tumor growth remains unclear. In the present study, we found that host-derived endogenous CXCL10 production was dramatically augmented during subcutaneous B16F10 melanoma tumor growth and that host ablation of CXCL10 in Cxcl10-/- mice showed a decrease in both angiogenesis and tumor growth of B16F10 melanoma in vivo. Several signaling pathways involved in production of pro-angiogenic factors and tumor growth were activated by CXCL10 in B16F10 melanoma cells. CXCL10 increased expression of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor subunit-B (PDGF-B), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and angiopoietin 2 (Angpt2), in B16F10 melanoma cells, resulting in enhanced tube formation and proliferation of human umbilical vein endothelial cells in vitro. In addition, CXCL10 directly enhanced B16F10 melanoma tumor growth in an in vitro three-dimensional cell culture system. Together, our findings reveal that amplified host-derived endogenous CXCL10 is critical for B16F10 melanoma angiogenesis and tumor growth. Therefore, CXCL10 might represent a therapeutic target for melanoma.

Up-regulated SLC25A39 promotes cell growth and metastasis via regulating ROS production in colorectal cancer.

Background: The mitochondrial transporter SLC25A39 has been implicated in the import of mitochondrial glutathione (mGSH) from the cytoplasm, crucial for mitigating oxidative stress and preserving mitochondrial function. Despite the well-established involvement of mitochondria in cancer, the functional impact of SLC25A39 on CRC progression remains elusive. Methods: The mRNA and protein expressions were detected by PCR, immunohistochemistry, and Western blot, respectively. Cell activity, cell proliferation, colony formation, and apoptosis were measured by CCK8 assay, EdU incorporation assay, plated colony formation assay, and flow cytometry, respectively. Cell migration was detected by wound healing and transwell chamber assay. The tumor microenvironment (TME), immune checkpoint molecules, and drug sensitivity of CRC patients were investigated using R language, GraphPad Prism 8 and online databases. Results: Here, we report a significant upregulation of SLC25A39 expression in CRC. Functional assays revealed that overexpression of SLC25A39 promoted CRC cell proliferation and migration while inhibiting apoptosis. Conversely, SLC25A39 knockdown suppressed cell growth and migration while enhancing apoptosis in vitro. Additionally, reduced SLC25A39 expression attenuated tumor growth in xenograft models. Mechanistically, elevated SLC25A39 levels correlated with reduced reactive oxygen species (ROS) accumulation in CRC. Furthermore, bioinformatic analyses unveiled the high SLC25A39 levels was associated with decreased expression of immune checkpoints and reduced responsiveness to immunotherapy. Single-cell transcriptomic profiling identified diverse cellular expression patterns of SLC25A39 and related immune regulators. Lastly, drug sensitivity analysis indicated potential therapeutic avenues targeting SLC25A39 in CRC. Conclusion Our findings underscore the pivotal role of SLC25A39 in CRC progression and suggest its candidacy as a therapeutic target in CRC management.

MISP-mediated enhancement of pancreatic cancer growth through the Wnt/ß-catenin signaling pathway is suppressed by Fisetin.

Pancreatic cancer is a highly malignant tumor characterized by high mortality and low survival rates. The mitotic interactor and substrate of Plk1 (MISP) is a cancer-associated protein that regulates mitotic spindle localization and is highly expressed in several malignant tumors, contributing to tumor development. However, the function and regulatory mechanisms of MISP in pancreatic cancer remain unclear. In this study, we analyzed RNA sequencing data related to pancreatic cancer from the TCGA and GEO databases, identifying MISP as a potential prognostic marker for the disease. MISP was significantly upregulated in pancreatic cancer cells and tissues compared to normal pancreatic cells and tissues. Notably, in pancreatic cancer cells, high MISP protein expression promoted cell proliferation and growth. Mechanistically, the upregulation of MISP facilitated the nuclear accumulation of ß-catenin, thereby activating the Wnt/ß-catenin signaling pathway and promoting pancreatic cancer growth. In search of effective inhibitors of MISP expression, we screened an FDA-approved drug library and identified Fisetin as a potential suppressor of MISP expression. Fisetin was found to downregulate the transcription factor MYB, thereby reducing MISP expression. Further experiments demonstrated that Fisetin effectively inhibited the in vitro and in vivo growth of pancreatic cancer by suppressing the MISP/Wnt/ß-catenin signaling axis. In summary, our research has identified MISP as a novel therapeutic target in pancreatic cancer and uncovered its associated regulatory mechanisms.

Honey and Aloe vera Solution Increases Survival and Modulates the Tumor Size In Vivo.

SCOPE: The combination of honey and Aloe vera is used as a popular complementary treatment for cancer due to their nutraceutical properties. This study aims to investigate the anticancer activity of honey and A. vera solution and its ethanolic extraction through in vitro and in vivo approaches. METHODS AND RESULTS: After comparisons of honey and A. vera (HA) solution and its ethanolic extraction solution (E) samples by UPLC-ESI-MS/MS, the study verifies HA-treatment affected only Walker tumor cells viability at the highest dose, and E-treatment has a more cytotoxic/antiproliferative effect in MCF-7 and Walker-256 cells. The in vivo results show a higher survival rate in Walker-256 tumor-bearing rats (WHA), with higher NK cell infiltration in tumor tissue and a tendency in the WE group. These results are possible due to decreased mannose-based immunomodulatory polysaccharides and aloin-A contents in the ethanolic extract solution compared to HA solution. CONCLUSION: The current study provides compelling evidence of selectively cytotoxic against tumor cells under honey and A. vera solution and ethanolic extraction solution treatment, due to the cytotoxic/antiproliferative compounds. Therefore, the use of honey and A. vera solution could be used as a basis for coadjuvant therapy in cancer treatment.