Tumor Research Articles

Myeloid activation clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer.

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.

Simultaneous targeting and suppression of heat shock protein 60 to overcome heat resistance and induce mitochondrial death of tumor cells in photothermal immunotherapy

As the most aggressive and metastatic subtype of breast cancer, clinical demands of triple negative breast cancer (TNBC) have far not been met. Heat shock protein 60 (HSP60) is over expressed in tumor cells and impair the efficacy of photothermal therapy. In this work, a conjugate composed of self-designed peptide targeting HSP60 and gold nanorods was constructed, referred to as AuNR-P17. Results showed that AuNR-P17 was able to simultaneously down regulate the level of HSP60 and locate in the mitochondria where HSP60 is enriched in the tumor cells of TNBC, which also impeded the interaction between HSP60 and integrin α3, thereby reducing the tumor cells' heat tolerance and metastatic capabilities. At the same time, AuNR-P17 induced remarkable mitochondrial apoptosis when exposed to the laser irradiation of 808 nm. The dual functions of AuNR-P17 led to the decrement of BCL-2 and the activation of p53 and cleaved caspase-3. The danger associated molecular patterns (DAMPs) generated from the mitochondrial apoptosis elicited strong and long-term specific immune responses against TNBC in vivo and ultimately inhibited the tumor metastasis and recurrence with significantly prolonged survival (>100 days) on TNBC mice. In conclusion, this study demonstrated HSP60 a promising potential therapeutic target for triple negative breast cancer and exhibited powerful capacity of AuNR-P17 in photothermal immune therapy.

Dual-targeting of tumor cells and tumor-associated macrophages by hyaluronic acid-modified MnO2 for enhanced sonodynamic therapy

In addition to tumor cells, M2-like tumor-associated macrophages (TAMs) also promote tumor progression. Accordingly, the strategy of targeted depletion or repolarization of M2-like TAMs becomes attractive. Here, we report a dual-targeting nanoagent SAMMH to tumor cells and M2-like TAMs for combinatorial tumor treatment. After co-loading the sonosensitizer spafloxacin (SPX) and oxidative phosphorylation inhibitor atavaquone (ATO) into hollow MnO2, the addition of Fe3+ and tannic acid-immobilized hyaluronic acid (HA) caused the formation of SAMMH through generating metal-polyphenol networks (MPNs) coatings outside. In vitro endocytosis assays demonstrated the efficient internalization of SAMMH by both tumor cells and M2-like TAMs through the specific CD44-HA interactions. The GSH-sensitive degradation of SAMMH results in the continuous release of SPX and ATO. Meanwhile, SAMMH could catalyze the endogenous H2O2 to extra O2, thus improving the therapeutic effect via the combination of Mn2+-induced CDT and O2-generation/O2-economy dual-enhanced sonodynamic therapy (SDT). Interestingly, SAMMH had a good targeted M2-like TAMs depleting capacity and could promote M2-to-M1 TAMs transformation by CDT-enhanced SDT, leading to a combinational anti-tumor effect. This dual-targeting nanoagent is a promising candidate to achieve CDT-enhanced SDT against both tumor cells and M2-like TAMs, thus providing new insights for the development of highly effective antitumor therapeutics.

Type I Diabetes Mellitus impairs cytotoxic immunity through CEACAM5 upregulation in colorectal cancer : Exploring the intersection of autoimmune dysfunction and cancer progression: the role of NF-κB p65 in colorectal cancer.

Type 1 diabetes (T1D) is characterized by an autoimmune-mediated destruction of pancreatic beta cells and a chronic inflammatory state, which may influence the progression of colorectal cancer (CRC) through immune system dysregulation and enhanced tumor immune evasion. This study aims to elucidate the role of p65 in modulating the tumor microenvironment in CRC within the context of T1D and to determine how this modulation affects tumor growth, immune cell infiltration, and the expression of immune evasion molecules such as CEACAM5. NOD mice, which model T1D, were inoculated with MC38 colon carcinoma cells engineered to knock down p65. Tumor growth was monitored, and the tumor microenvironment was analyzed using flow cytometry to assess the infiltration of immune cells. The expression of Ki-67 and CEACAM5 in tumor cells was also evaluated. Additionally, in vitro assays were conducted to study the proliferation and activation of T cells co-cultured with tumor cells. Knockdown of p65 in tumor cells significantly inhibited tumor growth in NOD mice. This was accompanied by an increased infiltration of cytotoxic CD8+ T cells and no significant change in CD4+ or Foxp3 + T regulatory cells within the tumor microenvironment. There was a notable reduction in the expression of Ki-67 and CEACAM5, indicating decreased proliferation and potential immune evasion capabilities of the tumor cells. Our findings demonstrate that the NF-κB p65 subunit plays a crucial role in promoting tumor growth and modulating the immune microenvironment in CRC, particularly in the context of T1D. Knocking down p65 not only reduces tumor progression but also enhances the anti-tumor immune response by decreasing immune evasion mechanisms. These results suggest that targeting the NF-κB pathway may be a viable strategy to improve the efficacy of cancer immunotherapy, especially in patients with autoimmune diseases like T1D. Physical activity enhances the effect of immune checkpoint blockade by inhibiting the intratumoral HIF1-α/CEACAM5 axis.

Fine-needle aspiration cytology of palisading adenocarcinoma: The first cytology report of a newly described salivary gland neoplasm.

Here, we report the first cytology findings of the newly characterized entity, palisading adenocarcinoma of the salivary gland, diagnosed in the sublingual gland of a 61-year-old female. The liquid-based cytology showed a moderately cellular aspirate containing three-dimensional clusters and trabeculae of tumor cells of various sizes. The cells had dark ovoid nuclei, finely granular chromatin, inconspicuous to punctate nucleoli, and ample cyanophilic cytoplasm with indistinct cell borders. In conventional smears, the cells displayed frequent crush artifacts and anisonucleosis resembling endocrine-type atypia. The background was clean, devoid of secretions, and contained singly dispersed tumor cells with stripped nuclei. Interestingly, concentrically laminated globules of extracellular matrix surrounded by the tumor cells were identified. Mitotic figures and tumor necrotic debris were absent. The cytologic findings correlated with the histologic findings of the excision specimen. The cytologic differential diagnosis and tumor grading of palisading adenocarcinoma were briefly discussed.

A comprehensive assessment of the antiproliferative effects of Cymbopogon winterianus essential oil, citronellal, and citronellal complexed with β-cyclodextrin on cervical cancer cell line (HeLa)

Cymbopogon winterianus. Jowitt (syn. Cymbopogon nardus. (L.) W. Watson var. mahapengiri. Winter) (Poaceae family) is native to tropical and semitropical areas of Asia, India, and Indonesia, and is cultivated in South and Central America. In this work, the antiproliferative potential of the essential oil of C. winterianus, its major compound against the HeLa cervical cancer lineage, as well as the major compound Citronellal complexed with β-cyclodextrin (β-CO) was evaluated. By gas chromatography coupled with mass spectrometry, it was possible to identify that Citronellal (38.89 %) is the major compound in C. winterianus. In vitro assays with cervical cancer cells (HeLa), it was possible to observe the antiproliferative activity of C. winterianus essential oil (CW), with IC50 of 1.86 μg/mL, as well as of the compound Citronellal (CO), IC50 4.44 μg/mL and citronellal complexed β-cyclodextrin (β-CO), IC50 2.59 μg/mL, as well as the evaluation of cell migration and cell cycle. NIH-3T3 non-tumor cells were also used to evaluate the selectivity of these compounds in tumor cells. All tested samples showed SI > 3, confirming the highest toxicity in tumor cells. All samples tested were able to decrease cell migration and when the proportion of cells in the Sub-G0 Phase was observed, all samples increased the proportion of cells with fragmented DNA, an indication of cell death, except for CW. Thus, it can be concluded that there is a potential to be explored in the C. winterianus essential oil, Citronellal, and Citronellal complexed with β-cyclodextrin.

Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review).

Cancer is a significant societal, public health and economic challenge in the 21st century, and is the primary cause of death from disease globally. Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) serves a crucial role in several biochemical processes, including adenosine triphosphate hydrolysis, purine metabolism and regulation of signaling pathways. Specifically, ENPP1, a type II transmembrane glycoprotein and key member of the ENPP family, may be upregulated in tumor cells and implicated in the pathogenesis of multiple human cancers. The present review provides an overview of the structural, pathological and physiological roles of ENPP1 and discusses the potential mechanisms of ENPP1 in the development of cancers such as breast, colon, gallbladder, liver and lung cancers, and also summarizes the four major signaling pathways in tumors. Furthermore, the present review demonstrates that ENPP1 serves a crucial role in cell migration, proliferation and invasion, and that corresponding inhibitors have been developed and associated with clinical characterization.

Discovery of potent hypoxia-inducible factor-1α (HIF-1α) degraders by proteolysis targeting chimera (PROTAC)

Under hypoxic conditions in tumor cells, HIF-1α is unable to bind to VHL E3 ligase due to the blocked hydroxylation reaction, resulting in impaired degradation and intracellular accumulation. Mounting evidences show a close association between HIF-1α overexpression and drug resistance, treatment failure, and increased mortality. To address this, we innovatively introduced an E3 ligase ligand to the HIF-1α inhibitor IDF-11774 using the PROTACs strategy, aiming to reactivate the degradative pathway impeded under hypoxia, and thereby achieve the redegradation of HIF-1α protein. Western blotting analyses demonstrated that most of we synthesized compounds effectively degraded HIF-1α. Among these, compounds C3 and V2 exhibited excellent anti-proliferation activity on 231 cells with IC50 values of 48.98 μM and 7.54 μM, respectively. Both compounds induced protein degradation in a concentration-dependent manner, achieving degradation rates up to 80 %. Additionally, this degradation was inhibited by the proteasome inhibitor MG132. As a part of the ongoing effort to develop HIF-1 inhibitors, targeting the degradation of HIF-1α may offer an effective treatment against solid tumors.

Clear cell stromal tumor of the lung: Report of 3 cases with emphasis on multifocal tumors.

We describe 3 patients with clear cell stromal tumor (CCST) of the lung, all of whom presented with multifocal disease. The patients were 2 men and 1 woman aged 47-58 years (mean, 54 years). Two patients had evidence of autoimmune disease and their pulmonary disease was an incidental finding; one patient presented with non-specific respiratory symptoms. Radiologic imaging revealed multiple pulmonary nodules in all patients. Histologically, the tumors were solid-cystic and composed of cytologically bland, medium-sized ovoid to spindle cells with eosinophilic to clear cytoplasm arranged in a subtle nested pattern. These tumor cells were set in a highly vascularized stroma. Occasional cytologic atypia with multinucleated tumor cells was noted but mitotic activity was low. An infiltrate of mixed inflammatory cells was apparent in all tumors. Immunohistochemical analysis demonstrated diffuse expression of vimentin and TFE3 in all cases. Next generation sequencing revealed the presence of YAP1::TFE3 fusion in 1/1 case. All patients have remained alive albeit with stable or progressive disease, 24-66 months after diagnosis. These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.

Hyaluronic acid-functionalized MOFs for combined sunitinib and siRNA therapy in renal cell carcinoma

Sunitinib is a first-line treatment for renal cell carcinoma (RCC), but suffers from drug resistance, causing therapy failure. Therefore, nano-scale delivery systems should be introduced for targeted delivery. Metal-organic frameworks (MOFs) are attractive drug carriers that not only enable multidrug combination therapies but also exert photodynamic effects by incorporating photosensitizers as components. Here, a Zr-based porphyrinic nanoscale MOF, PCN224, was prepared as the carrier for the co-delivery of sunitinib and the siRNA against vascular endothelial growth factor receptor-2 (VEGFR-2). Drug-loaded PCN-224 is coated with hyaluronic acid (HA) to prevent drug molecular leakage and to exert tumor-targeting effects (CD44 in tumor cells). Photodynamic therapy was conducted under 660 nm laser (50 mW·cm−2, 10 min) irradiation. Compared with St/siVEGFR-2@PCN-224@HA without the HA coating, St/siVEGFR-2@PCN-224@HA significantly suppressed cell viability and promoted cell apoptosis. Laser irradiation further increased the anti-cancer effect of St/siVEGFR-2@PCN-224@HA by generating cytotoxic ROS. H&E staining of major organs revealed no signs of damage, indicating the biosafety of St/siVEGFR-2@PCN-224@HA. The prepared St/siVEGFR-2@PCN-224@HA system enables triple inhibition of tumor growth via a combination of targeted therapy and genetic and photodynamic therapy to enhance the therapeutic effects on RCC.

Expression of cancer stem cell markers (CD24, CD44 & ALDH1A3 isoform) in Breast Cancer in Indian population considering clinicopathological characteristics and response to neoadjuvant chemotherapy - a prospective analysis from a university hospital.

Cancer stem cells (CSC) are a small number of tumour propagating cells present in the bulk of tumour cells. Expression of biological markers for CSCs viz. cluster of differentiation 24 and 44 (CD24, CD44) and aldehyde dehyodeganse 1 (ALDH1) imply aggressive tumour cell behaviour and poorer outcome, particularly in breast cancer. N = 75 Tumor tissue samples from enrolled breast cancer patients were obtained and subjected to histopathological examination and immunohistochemistry (IHC) after informed consent from patients. In addition to the estrogen receptor, progesterone receptor, Her2 neu receptor, and Ki67 index; IHC was also performed for CD24, CD44 and ALDH1A3 expression. These markers' positivity was correlated with clinical parameters, therapy response and metastasis prognostication. Most patients had higher tumor stage and high nodal burden (81.3% with node positivity; N1-68%, N2 -6.6%, N3-6.6%). Study showed significant association of CD24-/CD44 + group (p = 0.021) with distant metastasis and significant association of CD24-/CD44 + /ALDH1A3 + (p = 0.008) with higher stage (T4 stage). Tumor tissues expressing CD24-/CD44 + /ALDH1A3 + group (p = 0.010) and CD24 + /CD44 + / ALDH1A3 + (p = 0.010) were significantly associated with poor response to treatment. The correlation of CD24-/CD44 + was also statistically significant (p = 0.009). Positive expression of either CD24 and/or CD44 presented with aggressive disease, larger tumours and heavy nodal burden at a younger age. Additionally, ALDH1A3 positivity signified higher metastasis rates. CD24-/CD44 + /ALDH1A3 + and CD24 + /CD44 + / ALDH1A3 + correlated with greater chances of distant metastasis, aggressive disease, limited response to chemotherapy and poorer prognosis. Thus, these observations establish the role of these CSC phenotypes as important factors for prognostic outcomes and predictors of adverse outcomes. CD24-/CD44 + /ALDH1A3 + expression could serve as an important prognostic marker and predictor of adverse outcomes in Indian breast cancer tumour biology.

β-cyclodextrin-modified carboxymethyl chitosan/hyaluronic acid-based crosslinked composite nanogels as a dual responsive carrier for targeting anti-tumor therapy.

Advanced nanosized drug delivery systems can significantly improve efficacy and safety of first-line chemotherapeutics by enhancing tumor targeting. Herein, one-pot covalent crosslinking approach was developed to generate biodegradable tumor-targeted composite Nanogels from carboxymethyl chitosan, hyaluronic acid, cystamine and 6-ethylene-diamine-6-deoxy-β-cyclodextrin loaded with doxorubicin (DOX) for controlled intracellular DOX release. The optimized synthetic procedures generated Nanogels of about 190 nm in size and 28.3 % drug loading capability. DOX-loaded Nanogels was effectively internalized into tumor cells mainly by CD44 receptor-mediated endocytosis and rapidly released DOX in response to the high level of GSH in cytoplasm and acidic intracellular environments. DOX-loaded Nanogels significantly inhibited the tumor growth especially without appreciable side toxicities in 4 T1 tumor-bearing mice model owing to CD44 receptor-mediated active targeting and the passive targeting of Nanogels by enhanced permeation and retention effect. Overall, our newly developed composite Nanogels might be employed as a potentially effective therapeutic strategy for tumor therapy.

Role of Relaxin Signaling in Cancer: A Review.

The investigation into relaxin (RLN), additional RLN-like proteins, and RLN family peptide receptors (RXFP) has demonstrated their role in modulating the extracellular matrix (ECM), immune cells, specifically macrophages, and angiogenesis, with recent evidence showing an effect on signaling pathways in tumor cells. These findings serve as the basis for our narrative review to collate pertinent studies in this field and provide our perspective on their clinical and investigational significance. In the article, we discuss findings from pertinent studies focusing on evaluating the expression or effect of RLN1, RLN2, or RXFP1 in various cancers. We also briefly discuss the potential role that other RLN family peptides and their receptors play in cancer. Specifically, we delve into questions regarding RLN signaling in terms of parity/pregnancy-associated protection from mammary tumors, expression in tumors, detection in serum in the setting of cancers, effect on tumor-adjacent cells, effect on tumorigenesis depending on endogenous expression or delivery, and last, but not the least, impact on the effectiveness of anti-cancer therapies. We expect that summarizing the available literature to answer these questions will allow readers to understand the role of RLN-receptor interaction in cancer as well as identify areas of uncertainty and avenues for future investigation.

The oncomicrobiome: New insights into microorganisms in cancer.

The discoveries of the oncomicrobiome (intratumoral microbiome) and oncomicrobiota (intratumoral microbiota) represent significant advances in tumor research and have rapidly become of key interest to the field. Within tumors, microorganisms such as bacteria, fungi, viruses, and archaea form the oncomicrobiota and are primarily found within tumor cells, immunocytes, and the intercellular matrix. The oncomicrobiome exhibits marked heterogeneity and is associated with tumor initiation, progression, metastasis, and treatment response. Interactions between the oncomicrobiome and the immune system can modulate host antitumor immunity, influencing the efficacy of immunotherapies. Oncomicrobiome research also faces numerous challenges, including overcoming methodological issues such as low target abundance, susceptibility to contamination, and biases in sample handling and analysis methods across different studies. Furthermore, studies of the oncomicrobiome may be confounded by baseline differences in microbiomes among populations driven by both environmental and genetic factors. Most studies to date have revealed associations between the oncomicrobiome and tumors, but very few have established mechanistic links between the two. This review introduces the relevant concepts, detection methods, sources, and characteristics of the oncomicrobiome. We then describe the composition of the oncomicrobiome in common tumors and its role in shaping the tumor microenvironment. We also discuss the current problems and challenges to be overcome in this rapidly progressing field.

1,5- diaryl pyrazole-loaded chitosan nanoparticles as COX-2 inhibitors, mitigate neoplastic growth by regulating NF-κB pathway in-vivo zebrafish model

Non-steroidal anti-inflammatory drugs (NSAIDs) have been researched for their capacity to reduce cancer incidence, primarily due to their COX-2 inhibition properties. However, concerns have arisen regarding the precision of their targeting abilities. Nanoparticle approaches are revolutionizing cancer treatment by enabling targeted drug delivery, which enhances the efficacy and reduces the toxicity of chemotherapy. Particularly, chitosan-based nanoparticles are noteworthy for their biocompatibility, biodegradability, and ability to improve drug delivery. In this study, we synthesized folic acid-conjugated, 1,5-diaryl pyrazole-loaded chitosan (FA-CS-DP) nanoparticles using the ionic gelation method. The bioavailability and anti-neoplastic effects in a 7,12-dimethylbenzanthracene (DMBA)-exposed zebrafish model was investigated. MTT assay showed dose-dependent cytotoxicity of FA-CS-DP nanoparticles against MCF-7 breast cancer. The nanoparticles showed no toxicity to zebrafish embryos up to 100 μg/mL. The nanoparticle reduced oxidative stress and enhanced apoptosis in zebrafish exposed to DMBA. The morphological examination suggests that tumor growth was prevented in the zebrafish's surface and internal regions. The gene expression analysis confirmed the decrease in the expression of anti-inflammatory genes, such as cox-2 and nf-κb, and apoptosis inhibitor genes, such as bcl-2 and mdm2. By regulating the anti-inflammatory and apoptosis inhibitor genes, FA-CS-DP nanoparticle prevents neoplastic growth in the zebrafish model.

Saprophytic fungus (Ganoderma sessile) restrained Treg recruitment in the tumor microenvironment by down-regulating CCL28/CCR10 pathway

Ganoderma sessile, a saprophytic fungus, is a traditional Chinese medicinal material used in Chinese folk medicine and cuisine for its potential to enhance cancer patients immunity in clinical practice. However, the underlying mechanisms of its therapeutic effects remain elusive. Therefore, we explored the edible value to determine the underlying mechanisms of GS through multiple breast cancer models. GS was found to suppress tumor growth and lung metastasis, and prolong survival after surgery. It significantly increased tumor-infiltrating CD44HiCD62LHiCD8+ TCM cells while decreasing CD4+CD25+CD127− Treg cells in both lymph nodes and tumors. The mechanism behind GS’s effects primarily involved modulation of the Hif1-a/CCL28 pathway associated with Treg recruitment. Furthermore, GS could reduce CCR10 levels on the surface of Tregs. Collectively, GS inhibits tumor growth and pulmonary metastasis by restraining Treg recruitment through downregulation of the CCL28/CCR10 pathway—a finding which highlights its potential as a natural anti-tumor immune agent warranting further exploration.

Ultrasonication outperforms electroporation for extracellular vesicle cargo depletion

Extracellular vesicles (EVs), submicron-sized membranous structures released by cells, serve as vehicles of tissue-specific proteins and nucleic acids, facilitating intercellular communication and playing roles in pathophysiological processes. Leveraging their unique characteristics, EVs have emerged as promising drug delivery nanocarriers. Electroporation (EP) and ultrasonication (US) are among the prevalent techniques used for loading exogenous drugs into EVs owing to their simplicity and efficiency. However, the effectiveness of the two methods in depleting initial EV cargo has been overlooked. But this information is indispensable, as the bioactive residuals of EVs, notably derived from tumor or stem donor cells, may impact downstream therapeutic effects. Bridging this knowledge gap, therefore, can guide the selection of optimal drugs and loading methods tailored to therapeutic objectives. Here, we used high-throughput sequencing to investigate the protein and small RNA cargo of EVs treated with EP and US, respectively. We found that US exhibits higher efficacy in depleting EV cargo compared to EP, while US may also deplete essential endogenous molecules for combination therapy. Neither method demonstrated significant selectivity in cargo depletion, but they might preferentially retain few specific molecules. Additionally, membrane proteins are more prone to loss during US and EP treatments than cytoplasmic proteins.

Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells.

Two major antigen processing pathways represent protein Ags through major histocompatibility complexes (MHC class I and II) or lipid Ags through CD1 molecules influence the tumor immune response. Invariant Natural Killer T cells (iNKT) manage a significant role in cancer immunotherapy. CD1d, found on antigen-presenting cells (APCs), presents lipid Ags to iNKT cells. In many cancers, the number and function of iNKT cell are compromised, leading to immune evasion. Additionally impaired motility of iNKT cells may contribute to poor tumor prognosis. Emerging evidences suggest that CD1d, itself also influences cancer progression. Patient databases further highlight the importance of CD1d expression in different cancers and its correlation with patient survival outcomes. The ability of iNKT cells to activate and enhance the immune response renders them an attractive target for cancer immunotherapy. This review discusses all the possible ways of cancer immune evasion and restoration of immune responses mediated by CD1d-iNKT interactions.

Correlation of NAT10 expression with clinical data and survival profiles in esophageal squamous cell carcinoma patients, and its impact on cell proliferation and apoptosis.

This study investigates the association between NAT10 expression and clinical parameters while assessing prognostic outcomes in esophageal squamous cell carcinoma (ESCC) patients. Furthermore, the study seeks to elucidate the functional role of NAT10 in neoplastic cell proliferation and apoptosis. NAT10 expression was assessed in ESCC tissue microarrays through immunohistochemistry (IHC) tests. We employed SPSS software to analyze the correlation between NAT10 staining data, clinical indicators, and their implications for patient prognosis. Small interference RNA (siRNA) was utilized to inhibit NAT10 expression in two esophageal cancer cell lines, TE-1 and KYSE150. Subsequently, we meticulously quantified and compared cellular proliferation and apoptotic ratios among experimental groups. NAT10, Ki67, and Caspase3 expression levels in different groups were evaluated using quantitative polymerase chain reaction (qPCR) and Western blot (WB) assays. Statistical analyses were conducted using GraphPad Prism software, with significance at P<0.05. Our findings indicate that NAT10 is overexpressed in ESCC tissues and exhibits a significant correlation with tumor diameter and overall patient survival. Decreasing NAT10 expression led to the inhibition of tumor cell proliferation and the promotion of apoptosis. Furthermore, siRNA-mediated NAT10 inhibition resulted in the downregulation of Ki67 expression and the concomitant upregulation of Caspase3. The observed overexpression of NAT10 in ESCC tissues is associated with larger tumor diameters and reduced patient survival. NAT10 appears to play a pivotal role in the progression of esophageal cancer by influencing cell proliferation and apoptosis. These findings suggest potential clinical implications, with Ki67 and Caspase3 potentially participating in this intricate molecular biological process.

COX-2 in lung cancer: Mechanisms, development, and targeted therapies.

Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.