Biological evaluation of 9-thioansamitocin P3.

Highly cytotoxic maytansine derivatives are widely used in targeted tumor delivery. Structure-activity studies published earlier suggested the C9 carbinol to be a key element necessary to retain the potency. However, in 1984 a patent was published by Takeda in which the synthesis of 9-thioansamitocyn (AP3SH) was described and its activity in xenograft models was shown. In this article we summarize the results of an extended study of the anti-tumor properties of AP3SH. Like other maytansinoids, it induces apoptosis and arrests the cell cycle in the G2/M phase. It is metabolized in liver microsomes predominately by C3A4 isoform and doesn't inhibit any CYP isoforms except CYP3A4 (midazolam, IC50 7.84 µM). No hERG inhibition, CYP induction or mutagenicity in Ames tests were observed. AP3SH demonstrates high antiproliferative activity against 25 tumor cell lines and tumor growth inhibition in U937 xenograft model. Application of AP3SH as a cytotoxic payload in drug delivery system was demonstrated by us earlier.

Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: a phase II trial.

BACKGROUND: Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. METHODS: In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). RESULTS: From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1-5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6-52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8-8.2) months, and the median overall survival was 24.5 (95%CI: 10.2-38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. CONCLUSIONS: Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018).

Blockage of transferred exosome-shuttled miR-494 inhibits melanoma growth and metastasis.

There is emerging evidence of bioactive material transport by exosomes in melanoma. However, the functions of exosome content underlying such cancer progression remain largely unknown. We aimed at determining whether exosome secretion contributes to cellular microRNA-494 (miR-494) loss and investigated the roles of miR-494 in melanoma progression. The exosomes from blood serum and cell culture conditioned media were separated by ultracentrifugation. A short hairpin RNA was used to silence rab27a for inhibiting exosome release. To address the functional role of exosomal miR-494, we assessed cell proliferation, migration, invasion capabilities, and cell apoptosis. Finally, subcutaneous xenograft and lung-metastasis models were constructed to determine the effect of exosomal miR-494 in vivo. Based on long noncoding RNA microarray analysis of melanocyte and melanoma-derived exosomes from the Gene Expression Omnibus database, we discovered that miR-494 was enriched in melanoma-derived exosomes. And miR-494 was increased in exosomes secreted from melanoma patients' serum and A375 cells. Rab27a depletion reduced exosome secretion and rescued the abundance of cellular miR-494. Functional studies revealed that knockdown of rab27a and subsequent accumulation of miR-494 significantly suppressed the malignant phenotypes of melanoma cells via inducing cell apoptosis. Nude mice experiments confirmed that tumor growth and metastasis were suppressed by increasing miR-494 accumulation after rab27a depletion. In conclusion, blocking transferred exosome-shuttled miR-494 is a potential therapeutic option for melanoma.

Clinical value of Naa10p and CEA levels in saliva and serum for diagnosis of oral squamous cell carcinoma.

BACKGROUND: N-α-acetyltransferase 10 protein (Naa10p) is a potential prognostic biomarker that modulates the phenotypes of several cancer types. Carcinoembryonic antigen (CEA) is currently the most well-known biomarker for the detection of epithelial malignancies. Our objective was to evaluate the clinical value of Naa10p, CEA, and their combined detection for diagnosis of oral squamous cell carcinoma (OSCC). METHODS: This study included 202 individuals: 112 patients with OSCC, 30 patients with oral premalignant lesions (OPMLs), and 60 cancer-free and without OPML patients as control. Naa10p and CEA were determined in serum and saliva samples utilizing enzyme-linked immunosorbent assays. RESULTS: Salivary and serum levels of Naa10p and CEA in OSCC patients were significantly higher than those detected in OPML and the control groups, although patients with OPMLs also showed increased salivary and serum Naa10p and CEA levels as compared to the control group. Salivary Naa10p level in OSCC patients is correlated with the degree of differentiation and lymph node metastasis, and serum Naa10p level is specifically correlated with patient age. Additionally, salivary CEA level is correlated with the clinical stage and lymph node metastasis, whereas serum CEA level is correlated with lymph node metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value of combined detection were greater than any single detection. CONCLUSIONS: Combined use of salivary Naa10p and CEA as tumor markers for OSCC was more sensitive than serum Naa10p and CEA. These results indicated that combined detection of salivary Naa10p and CEA improved diagnostic performance and early detection rate for OSCC.

[Chemical Constituents from Glycosmis pentaphylla].

Objective: To study the chemical constituents of Glycosmis pentaphylla. Methods: 95% ethanolic extract of Glycosmis pentaphylla was fractioned and separated extensively by silica gel, Sephadex LH-20 chromatography,their structures were elucidated by means of spectral data analysis. Results: All compounds were isolated and identified as 5,7,4'-trihydroxydihydroflavonol( 1),aromadendrin( 2),trans-dihydroquercetin( 3),cis-dihydroquercetin( 4),kaempferol( 5),quercetin( 6),5,7,4'-trihydroxyflavonol-3-O-α-L-rhamnopyranoside( 7),quercetin-3-O-α-L-arabinofuranoside( 8),quercetin-3-O-α-L-rhamnopyranoside( 9),5,7,3',4'-tetrahydroxyflavonone-3-O-rhamnopyranoside( 1→6) glucopyranoside( 10) and 5,7,3'-trihydroxy-4'-methyl ether-flavonone-3-O-rhamnopyranoside( 1→6) glucopyranoside( 11). Conclusion: All compounds are isolated from this plant for the first time.

Expression of TGFß-1 and EHD1 correlated with survival of non-small cell lung cancer.

Transforming growth factor-ß1 (TGFß-1) signaling is regulated by endocytotic pathway. To clarify the prognostic value of TGFß-1 and to verify the involvement of endocytosis in drug resistance, we examined the expression of TGFß-1 and Eps15 homology domain 1 (EHD1) in non-small cell lung cancer (NSCLC) and its association with tumor characteristics and survival of patients with NSCLC. Expression of TGFß-1 and EHD1 was evaluated by immunohistochemistry in paraffin sections from 105 NSCLC patients. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazard regression model. Positive immunostaining of TGFß-1 and EHD1 was detected in 52.38 and 39.05 % of NSCLC samples, respectively. In non-adjuvant chemotherapy-treated group (P = 0.006) and epidermal growth factor receptor (EGFR) (+) group (P = 0.038), patients with TGFß-1 expression had a longer OS. EHD1 negative expression predicted a longer OS (P = 0.003), especially in EGFR (+) (P = 0.006) and adjuvant chemotherapy-treated patients (P = 0.003). NSCLC patients with concurrent positive TGFß-1 and negative EHD1 (combined markers) were significantly correlated with better OS (P = 0.001). American Joint Committee on Cancer (AJCC) status and combined markers were independent prognostic indicators for OS (HR (95 % CI) 1.576 (1.112-2.232), P = 0.011 and HR 0.349 (0.180-0.673), P = 0.002, respectively). We identified concordant TGFß-1 positive and EHD1 negative as a strong favorable prognosis factor in NSCLC. Our results may help us to select and optimize strategies for individualized therapy.

Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture.

A fribotic tumor microenvironment promotes progression of cancer. In this study, we utilize a reconstituted basement membrane mimics Matrigel based three-dimensional organotypic culture (rBM 3-D) to investigate the mechanisms that mediate the tumor promoting effects of the fibrogenic mediators TGF-ß1 and type I collagen (Col-1) on lung adenocarcinoma cells. Similar to normal alveolar epithelial cells, the well-differentiated lung adenocarcinoma cells in rBM 3-D culture undergo acinar morphogeneis that features polarized epithelial cell spheres with a single central lumen. Either TGF-ß1 or Col-1 modestly distorts acinar morphogenesis. On the other hand, TGF-ß1 and Col-1 synergistically induce a transition from acinar morphology into stellate morphology that is characteristic of invasive and metastatic cancer cells. Inhibition of the Src kinase activity abrogates induction of stellate morphology, activation of Akt and mTOR, and the expression of tumor promoting genes by TGF-ß1 and Col-1. To a similar extent, pharmacological inhibition of mTOR abrogates the cellular responses to TGF-ß1 and Col-1. In summary, we demonstrate that TGF-ß1 and Col-1 promote stellate morphogenesis of lung cancer cells. Our findings further suggest that the Src-Akt-mTOR axis mediates stellate morphogenesis. These findings also indicate that rBM 3-D culture can serve as an ideal platform for swift and cost-effective screening of therapeutic candidates at the interface of the tumor and its microenvironment.

Valproic acid suppresses cervical cancer tumor progression possibly via activating Notch1 signaling and enhances receptor-targeted cancer chemotherapeutic via activating somatostatin receptor type II.

PURPOSE: We investigated the effects of the anti-epilepsy drug valproic acid (VPA) alone and in combination in treating cervical cancer. METHODS: VPA was investigated for its effects on cervical cancer Hela cell proliferation and tumor growth via in vitro and in vivo assays. RESULTS: VPA induce cell growth suppression and cell cycle arrest, with an increase of Notch1 that acts as a tumor suppressor and the change of other tumor-associated genes such as p21, p63 and PCNA. VPA was also found to induce cell morphological change, with an increase of certain cell transformation markers such as snail1, snail2 and N-cadherin. Moreover, VPA could significantly up-regulate somatostatin receptor type II (SSTR2). Our in vivo study further demonstrated that VPA via inducing SSTR2 up-regulation extremely enhanced the anti-tumor ability of the SSTR2-preferential cytotoxic COL-SST conjugate in xenografts. CONCLUSIONS: VPA could not only suppress tumor progression but also provide a novel promising therapeutic choice in combination with a receptor-targeted cytotoxic conjugate via activating the specific receptor.

Fluorescence origin and chirality mechanism of graphene quantum Dots: Twist or Non-Twist?

In this paper, we theoretically investigate the fluorescence origin and chirality mechanism of graphene quantum dots with non-twist and twist geometries, respectively. It is revealed that twist is not necessary for fluorescence; but twist is must for the chirality, which can significantly enhance the intensity of chirality, demonstrated by ECD spectra. Our results provide deeper understanding on the physical mechanism of fluorescence and chirality of graphene quantum dot influenced by geometric twist.

Organic Solar Cells: Physical Principle and Recent Advances.

Organic solar cells (OSC) based on organic semiconductor materials that convert solar energy into electric energy have been constantly developing at present, and also an effective way to solve the energy crisis and reduce carbon emissions. In the past several decades, efforts have been made to improve the power conversion efficiency (PCE) of OSCs. During this period, a variety of structural and material forms of OSCs have evolved. Commercializing OSCs, extending their service life and exploring their future development are promising but challenging. In this review, we first briefly introduce the development of OSCs and then summarize and analyze the working principle, performance parameters, and structural features of OSCs. Finally, we highlight some breakthrough related to OSCs in detail.

Connectomic insight into unique stroke patient recovery after rTMS treatment.

An improved understanding of the neuroplastic potential of the brain has allowed advancements in neuromodulatory treatments for acute stroke patients. However, there remains a poor understanding of individual differences in treatment-induced recovery. Individualized information on connectivity disturbances may help predict differences in treatment response and recovery phenotypes. We studied the medical data of 22 ischemic stroke patients who received MRI scans and started repetitive transcranial magnetic stimulation (rTMS) treatment on the same day. The functional and motor outcomes were assessed at admission day, 1 day after treatment, 30 days after treatment, and 90 days after treatment using four validated standardized stroke outcome scales. Each patient underwent detailed baseline connectivity analyses to identify structural and functional connectivity disturbances. An unsupervised machine learning (ML) agglomerative hierarchical clustering method was utilized to group patients according to outcomes at four-time points to identify individual phenotypes in recovery trajectory. Differences in connectivity features were examined between individual clusters. Patients were a median age of 64, 50% female, and had a median hospital length of stay of 9.5 days. A significant improvement between all time points was demonstrated post treatment in three of four validated stroke scales utilized. ML-based analyses identified distinct clusters representing unique patient trajectories for each scale. Quantitative differences were found to exist in structural and functional connectivity analyses of the motor network and subcortical structures between individual clusters which could explain these unique trajectories on the Barthel Index (BI) scale but not on other stroke scales. This study demonstrates for the first time the feasibility of using individualized connectivity analyses in differentiating unique phenotypes in rTMS treatment responses and recovery. This personalized connectomic approach may be utilized in the future to better understand patient recovery trajectories with neuromodulatory treatment.

The Suppressive Effect of Rebastinib on Triple-negative Breast Cancer Tumors Involves Multiple Mechanisms of Action.

BACKGROUND/AIM: High resistance of triple-negative breast cancer has prompted scientists to look for new targets susceptible to treatment. CDK16 has been suggested as a promising target whose inhibition can lead to tumor growth suppression. Rebastinib, a potent inhibitor of CDK16, has been reported to exhibit anti-tumor activity both in vitro and in vivo. MATERIALS AND METHODS: The anticancer activity of rebastinib was studied in vitro using cell proliferation, cell cycle arrest and cell apoptosis assays and in vivo in xenograft tumor models using MDA-MB-231 and MDA-MB-468-derived tumors. The safety and drug-like properties of rebastinib were assessed using a panel of Absorption, Distribution, Metabolism, and Excretion (ADME) assays, Ames tests, human Ether-a-go-go Related Gene (hERG) experiments and pharmacokinetic studies in mice and rats. RESULTS: Rebastinib demonstrates antitumor activity against breast cancer both in vitro and in vivo. However, the response of the tumor strongly depends on the type of triple-negative breast cancer. Rebastinib-induced cell cycle arrest was observed in G0/G1 phase suggesting a more complex mechanism than just CDK16 inhibition. ADME and PK studies confirmed the drug-like properties and reasonable safety of rebastinib. CONCLUSION: Our studies confirmed rebastinib to be a promising drug candidate for breast cancer treatment with high oral bioavailability and reasonable safety. Our data suggest that the mechanism of action of rebastinib is not limited to CDK16 inhibition but also involves other pathways. This does not diminish the importance of rebastinib as a drug candidate, but reveals the presence of several mechanisms, suggesting a wider scope of possible applications.

Notch1-mediated tumor suppression in cervical cancer with the involvement of SST signaling and its application in enhanced SSTR-targeted therapeutics.

The role of Notch signaling in cervical cancer is seemingly controversial. To confirm the function of Notch signaling in this type of cancer, we established a stable Notch1-activated cervical cancer HeLa cell line. We found that Notch1 activation resulted in apoptosis, cell cycle arrest, and tumor suppression. At the molecular level, we found that a variety of genes associated with cyclic AMP, G protein-coupled receptor, and cancer signaling pathways contributed to Notch1-mediated tumor suppression. We observed that the expression of somatostatin (SST) was dramatically induced by Notch1 signaling activation, which was accompanied by enhanced expression of the cognate SST receptor subtype 1 (SSTR1) and SSTR2. Certain genes, such as tumor protein 63 (TP63, p63), were upregulated, whereas others, such as B-cell lymphoma 2 (BCL-2), Myc, Akt, and STAT3, were downregulated. Subsequently, knockdown of Notch1-induced SST reversed Notch1-induced decrease of BCL-2 and increase of p63, indicating that Notch1-induced tumor suppression may be partly through upregulating SST signaling. Our findings support a possible crosstalk between Notch signaling and SST signaling. Moreover, Notch-induced SSTR activation could enhance SSTR-targeted cancer chemotherapy. Valproic acid (VPA), a histone deacetylase inhibitor, suppressed cell growth and upregulated the expression of Notch1 and SSTR2. A combination therapy with VPA and the SSTR2-targeting cytotoxic conjugate CPT-SST strongly led to greater suppression, as compared to each alone. Our findings thus provide us with a promising clinical opportunity for enhanced cancer therapy using combinations of Notch1-activating agents and SSTR2-targeting agents.

Transcriptome sequencing reveals circRNA expression profile in Parkinson's disease-like mice after aerobic exercise.

Parkinson's disease (PD) is a common complex neurodegenerative disease, and aerobic exercise (EX) has potential to improve motor dysfunction. This study aimed to explore whether EX acts on PD in mice mode. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and subjected to a 4-week physical exercise regimen (EX-PD group) and underwent RNA-Seq. Here, MPTP caused PD, which was characterized by neuron shrinkage and behavioral deficits, whereas EX improved PD by rescuing neuronal survival and motor function in mice. Moreover, circRNA expression profiles identified a total of 142 differentially expressed circRNAs (DEcircRNAs) between PD and EX-PD group. These DEcircRNAs were mainly involved in PD, dopaminergic synapses, and calcium signaling pathways. The expression of circZfp827 and circTshz2 were significantly elevated in PD group while reduced owing to EX intervention. In contrast, EX intervention significantly restored decline in circHivep2 expression due to PD. The circRNA-miRNA-mRNA network suggested that circZfp827, circHivep2, and circTshz2 were involved in ceRNA mechanism of EX to improve PD, and their target genes were significantly decreased after interference. The directly binding regulation relationship of circTshz2-mmu-miR-326-3p-Th was verified by double luciferase reporter assay. Our research revealed that EX improved motor behavioral deficits and pathological features of PD mice, and circRNA-based signatures are potential candidates for further assessment as PD biomarkers for improvement by EX.

Bombesin-drug conjugates in targeted therapy for small cell lung cancer.

Small cell lung cancer (SCLC) is a aggressive form of primary lung neoplasm that often presents in elderly smokers. While stage I SCLC can be managed with surgery, extensive-stage disease is managed with chemotherapy using etoposide and cisplatin among other agents, and often complemented by radiation therapy to the chest and cranium. Recent advances in pharmacological research have yielded novel antibody and peptide-conjugated adjunctive chemotherapy, of which bombesin and bombesin receptors have played an important role due to their overexpression in SCLC and other lung cancers. Chemotherapy agents conjugated to bombesin or bombesin-like peptides often demonstrate higher therapeutic efficacy, greater treatment specificity, as well as improved cytotoxicity towards SCLC cells that demonstrate drug resistance. Further modifications to the bombesin-drug conjugate, such as liposomal preparation, have further enhanced bio-availability and half-life of the compound. Additionally, bombesin-radioisotope conjugates can be used for early detection of SCLC using positron emission tomography, as well as subsequent targeted adjuvant radiotherapy to help minimize radiation-induced fibrosis of healthy tissue. Ultimately, further studies are imperative to capitalize on the various applications of bombesin conjugates in both the diagnosis and management of SCLC.

Influence of aerobic exercise training on mice gut microbiota in Parkinson's disease.

Accumulating evidence shows that gut microbial dysbiosis may represent a risk factor for Parkinson's disease (PD). Exercise has a positive effect on microbiota in general. The effect of aerobic exercise training (AET) on the gut microbial environment in PD remains to be explored. Here, we performed the 16S rRNA gene sequencing on feces from sham operated-mice (sham), PD mice model, and mice receiving AET (AET). Results indicated that AET had no remarkable effect on species richness and bacterial diversity of PD mice. The relative abundance of the Bacteroidetes was reduced, while Firmicutes, Actinobacteria, Lactobacillaceae, Streptococcaceae, Lactobacillus, Streptococcus, Lactococcus, Lysinibacillus, Pelomonas, and Prevotellaceae_UCG-001 were increased in PD mice compared with those of sham operated-mice, whereas AET partly rescued their abundance. Additionally, the composition proportion of beneficial Lactobacillus_gasseri and uncultured_Erysipelotrichales_bacterium significantly increased in AET mice compared to PD mice. Moreover, discriminative bacteria, such as Bacilli, Lactobacillales, Lactobacillaceae, Lactobacillus, and Lactococcus were identified as a specific taxon in AET mice. Here we provide evidence that AET can improve the gut microbiota of PD mice.

Carbamazepine promotes Her-2 protein degradation in breast cancer cells by modulating HDAC6 activity and acetylation of Hsp90.

Histone deacetylase 6 (HDAC6) inhibition, recently, has been shown to promote the acetylation of heat-shock protein 90 (Hsp90) and disrupt its chaperone function. Her-2 oncoprotein is identified as a client protein of Hsp90. Therefore, in this study we examined the effect of carbamazepine, which could inhibit HDAC on Hsp90 acetylation and Her-2 stability. The results of this study demonstrate that while carbamazepine had no effect on the Her-2 mRNA level, it induced Her-2 protein degradation via the proteasome pathway by disrupting the chaperone function of Hsp90 in SK-BR-3 cells. Mechanistically, carbamazepine could enhance the acetylation of α-tubulin, indicating its inhibitory effect on HDAC6. Functionally, carbamazepine could synergize with trastuzumab or geldanamycin to promote Her-2 degradation and inhibit breast cancer cell proliferation. Thus, this study has potential clinical implications by providing a promising strategy to overcome the development of resistance against trastuzumab therapy for breast cancer.

The COVID-19 pandemic and the potential treatment of the novel coronavirus SARS-CoV-2.

Coronavirus SARS-CoV-2 is a novel coronavirus and the seventh that can infect human beings and result in severe and acute respiratory syndrome and deaths. Currently, the world is undergoing a global health emergency due to the SARS-CoV-2 pandemic. As of May 18, SARS-CoV-2 has spread to over two hundred countries and infected more than 4.8 million people, resulting in over 300,000 deaths since the first case of a novel pneumonia (COVID-19) patient was discovered in Wuhan, China at the end of December 2019. Currently, there are no effective and/or approved targeting drugs for it though various supportive therapy drugs such as small molecule drugs, vaccines, antibodies and even Chinese herb medicines have been used in the treatment of the first-line patients. However, certain drugs such as remdesivir and S416 are under clinical investigation and may become therapeutic drugs. In this article, we review and discuss SARS-CoV-2, its person-to-person transmission, genomics and proteomics, and the potential for drug development.

NEFM DNA methylation correlates with immune infiltration and survival in breast cancer.

BACKGROUND: This study aims to determine whether NEFM (neurofilament medium) DNA methylation correlates with immune infiltration and prognosis in breast cancer (BRCA) and to explore NEFM-connected immune gene signature. METHODS: NEFM transcriptional expression was analyzed in BRCA and normal breast tissues using Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The relationship between NEFM DNA methylation and NEFM transcriptional expression was investigated in TCGA. Potential influence of NEFM DNA methylation/expression on clinical outcome was evaluated using TCGA BRCA, The Human Protein Atlas and Kaplan-Meier plotter databases. Association of NEFM transcriptional expression/DNA methylation with cancer immune infiltration was investigated using TIMER and TISIDB databases. RESULTS: High expression of NEFM correlated with better overall survival (OS) and recurrence-free survival (RFS) in TCGA BRCA and Kaplan-Meier plotter, whereas NEFM DNA methylation with worse OS in TCGA BRCA. NEFM transcriptional expression negatively correlated with DNA methylation. NEFM DNA methylation significantly negatively correlated with infiltrating levels of B, CD8+ T/CD4+ T cells, macrophages, neutrophils and dendritic cells in TIMER and TISIDB. NEFM expression positively correlated with macrophage infiltration in TIMER and TISIDB. After adjusted with tumor purity, NEFM expression weekly negatively correlated with infiltration level of B cells, whereas positively correlated with CD8+ T cell infiltration in TIMER gene modules. NEFM expression/DNA methylation correlated with diverse immune markers in TCGA and TISIDB. CONCLUSIONS: NEFM low-expression/DNA methylation correlates with poor prognosis. NEFM expression positively correlates with macrophage infiltration. NEFM DNA methylation strongly negatively correlates with immune infiltration in BRCA. Our study highlights novel potential functions of NEFM expression/DNA methylation in regulation of tumor immune microenvironment.

Naa10p Enhances Chemosensitivity to Cisplatin in Oral Squamous Cell Carcinoma Cells.

BACKGROUND: This study aimed to investigate the function and underlying molecular mechanism of N-α-acetyltransferase 10 protein (Naa10p) in cisplatin (CDDP) chemosensitivity in oral squamous cell carcinoma (OSCC). METHODS: Salivary Naa10p levels in 76 OSCC patients undergoing CDDP-based chemotherapy were detected using enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction and Western blot were used to examine the expression of Naa10p in constructed CDDP-resistant OSCC cell (Cal-27/CDDP) lines and nude mouse model. In addition, the tumor volume and weight of nude mice were analyzed. Lentiviral system was employed to establish and identify OSCC cell lines with stable Naa10p interference or overexpression. MTT assay was used for drug sensitivity analysis. P-gp and Bcl-2 expression levels were tested by Western blot. RESULTS: Higher salivary Naa10p expression was present in the complete response/partial response group (n=46) compared to the stable disease/progressive disease group (n=30) in OSCC patients receiving chemotherapy treatment. Naa10p expression was down-regulated in Cal-27/CDDP cells and tissues. Naa10p overexpression significantly reduced the expression level of drug-resistant molecules. Naa10p was related to CDDP resistance and enhanced CDDP sensitivity in OSCC according to drug sensitivity analysis and nude mouse model experiments. CONCLUSION: Naa10p plays a tumor suppressor gene role and is associated with CDDP resistance in OSCC. It can enhance CDDP sensitivity in OSCC and may be a potential target for OSCC chemotherapy.