Background
CKLF-like MARVEL transmembrane domain-containing 6
(
CMTM6
) is a critical regulator of tumor immunology among various cancers. However, the role and underlying molecular mechanism of
...CMTM6
in oral squamous cell carcinoma (OSCC) progression remains unclear.
Methods
The expression of
CMTM6
,
PD-L1
and
CD163
in OSCC tissues were detected by immunohistochemistry on tissue microarray. The effect of
CMTM6
knockdown on OSCC cells and macrophage polarization were analyzed by CCK-8 assay, apoptotic assay, would-healing assay, transwell assay and qPCR. OSCC cell derived exosomes were obtained by ultracentrifugation and the mechanistic studies were conducted by qPCR and Western Blot. 4-Nitroquinoline N-oxide (4NQO) induced OSCC mice were used for verifying the effect of
CMTM6
downregulation on M2 macrophage infiltration and tumor growth.
Results
In OSCC samples, higher
CMTM6
expression has been obviously associated with higher pathological stage of OSCC patients,
CD163
+ macrophages infiltration and
PD-L1
expression.
CMTM6
knockdown of OSCC cells inhibited proliferative, migrative and invasive abilities of OSCC cells, as well as inhibited M2 macrophage polarization in vitro with downregulating
PD-L1
expression. Importantly, exosomes from OSCC cells shuttled
CMTM6
to macrophages and promoted M2-like macrophage polarization through activating ERK1/2 signaling. In addition, in 4NQO-induced OSCC mice,
CMTM6
level was positively associated with
CD163
,
CD206
and
PD-L1
as well as M2-like macrophage infiltration.
Conclusion
OSCC cell-secreted exosomal
CMTM6
induces M2-like macrophages polarization to promote malignant progression via ERK1/2 signaling pathway, revealing a novel crosstalk between cancer cells and immune cells in OSCC microenvironment.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Graphene quantum dots (GQDs) as novel nanomaterials, have received significant interest in the field of biomedical applications. It is worth noting that a large amount of research is devoted to ...GQDs-based nanocomposites for cancer treatment, especially for photodynamic therapy (PDT), in that they can act not only as more favorable photosensitizers (PSs) but also nanoplatforms for delivering PSs. In this review, the biological behavior and physicochemical properties of GQDs for PDT are described in detail, and the application of GQDs-based nanocomposites in improved PDT and PDT-based combination therapies is analyzed, which may provide a new strategy for designing efficient PDT systems for cancer treatment.
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•The synthesis methods of GQDs have important effects on their physicochemical properties.•GQDs exhibit excellent biocompatibility and optical properties.•GQDs have great potential in photodynamic therapy.•PDT-based combination therapies show good synergistic effects.•Precisely tailoring properties of GQDs plays a key role in their application.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to ...investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC.
Immunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured.
The number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS.
These indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Tumour vascular normalisation therapy advocates a balance between pro‐angiogenic factors and anti‐angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional ...Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported.
Methods
Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK‐8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF.
Results
Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL‐8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL‐8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART‐treated cells.
Conclusion
Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF‐signalling pathway.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Lymph node metastasis (LNM) is a risk factor for poor long-term outcomes and a prognostic factor for disease-free survival in colon cancer. Preoperative lymph node status evaluation ...remains a challenge. The purpose of this study is to determine whether tumor size measured by multidetector computed tomography (MDCT) could be used to predict LNM and N stage in colon cancer. Material and methods One hundred six patients with colon cancer who underwent radical surgery within 1 week of MDCT scan were enrolled. Tumor size including tumor length (Tlen), tumor maximum diameter (Tdia), tumor maximum cross-sectional area (Tare), and tumor volume (Tvol) were measured to be correlated with pathologic LNM and N stage using univariate logistic regression analysis, multivariate logistic analysis, and receiver operating characteristic (ROC) curve analysis. Results The inter- and intraobserver reproducibility of Tlen (intraclass correlation coefficient ICC = 0.94, 0.95, respectively), Tdia (ICC = 0.81, 0.93, respectively), Tare (ICC = 0.97, 0.91, respectively), and Tvol (ICC = 0.99, 0.99, respectively) parameters measurement are excellent. Univariate logistic regression analysis showed that there were significant differences in Tlen, Tdia, Tare, and Tvol between positive and negative LNM (p < 0.001, 0.001, < 0.001, < 0.001, respectively). Multivariate logistic regression analysis revealed that Tvol was independent risk factor for predicting LNM (odds ratio, 1.082; 95% confidence interval for odds ratio, 1.039, 1.127, p<0.001). Tlen, Tdia, Tare, and Tvol could distinguish N0 from N1 stage (p < 0.001, 0.041, < 0.001, < 0.001, respectively), N0 from N2 (all p < 0.001), N0 from N1-2 (p < 0.001, 0.001, < 0.001, < 0.001, respectively), and N0-1 from N2 (p < 0.001, 0.001, < 0.001, < 0.001, respectively). The area under the ROC curve (AUC) was higher for Tvol than that of Tlen, Tdia, and Tare in identifying LNM (AUC = 0.83, 0.82, 0.69, 0.79), and distinguishing N0 from N1 stage (AUC = 0.79, 0.78, 0.63, 0.74), N0 from N2 stage (AUC = 0.92, 0.89, 0.80, 0.89, respectively), and N0-1 from N2 stage (AUC = 0.84, 0.79, 0.76, 0.83, respectively). Conclusion Tumor size was correlated with regional LNM in resectable colon cancer. In particularly, Tvol showed the most potential for noninvasive preoperative prediction of regional LNM and N stage. Keywords: Colon cancer, Lymph node metastasis, Enhanced CT, Tumor size, N stage
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we ...identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT‐associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up‐regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann‐like cell through Twist/S100A4 axis in SACC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
High expression of δ‑like ligand 4 (Dll4) is reportedly related to the invasion, metastasis, and clinical prognosis of various malignant tumours. Our previous study revealed that collective cell ...invasion was a common pattern in salivary adenoid cystic carcinoma (SACC). However, the roles of the Dll4/Notch1 signalling pathway in the collective invasion of SACC remain unclear. The present study revealed that Dll4 expression was higher at the invasive front of SACC, and that this upregulation was associated with solid tumour type, high TNM grade, and high rates of metastasis and recurrence. Furthermore, the expression levels of Notch1 and Dll4 were positively correlated at the invasive front, and a three‑dimensional (3D) culture model revealed that leader cells showed high expression of Dll4, while follower cells showed high expression of Notch1. Moreover, silencing of Dll4 expression using small interfering RNA reduced the migration, invasion, and collective invasion of SACC cells, and these abilities were rescued by Notch1 overexpression. Finally, SACC collective invasion was increased via the Dll4/Notch1 signalling pathway in experiments that involved a stiff 3D gel, hypoxia and co‑culture with human endothelial cells. These findings indicated that the Dll4/Notch1 signalling pathway may be involved in the collective invasion of SACC, which may help to provide possible targets for the treatment of SACC.
Podophyllotoxin (PTOX) is a biologically active compound derived from the podophyllum plant, and both it and its derivatives possess excellent antitumor activity. The PTOX derivatives etoposide ...(VP-16) and teniposide (VM-26) have been approved by the U.S. Food and Drug Administration (FDA) for cancer treatment, but are far from perfect. Hence, numerous PTOX derivatives have been developed to address the major limitations of PTOX, such as systemic toxicity, drug resistance, and low bioavailability. Regarding their anticancer mechanism, extensive studies have revealed that PTOX derivatives can induce cell cycle G2/M arrest and DNA/RNA breaks by targeting tubulin and topoisomerase II, respectively. However, few studies are dedicated to exploring the interactions between PTOX derivatives and downstream cancer-related signaling pathways, which is reasonably important for gaining insight into the role of PTOX. This review provides a comprehensive analysis of the role of PTOX derivatives in the biological behavior of tumors and potential molecular signaling pathways, aiming to help researchers design and develop better PTOX derivatives.
Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate ...OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.
The circCPNE1/miR-330-3p axis inhibits oral squamous cell carcinoma (OSCC) progression. A miRNA delivery system (PP@miR NPs) coupled with cisplatin inhibits tumors and even achieves partial tumor regression. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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