Identification and validation of key genes in gastric cancer: insights from in silico analysis, clinical samples, and functional assays.

INTRODUCTION: The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental methods, to identify potential key genes and unveil the underlying pathogenesis and prognosis of GC. METHODS: Gene expression profiles from GEO databases (GSE118916, GSE79973, and GSE29272) were analyzed to identify DEGs between GC and normal tissues. A PPI network was constructed using STRING and Cytoscape, followed by hub gene identification with CytoHubba. Investigations included expression and promoter methylation analysis, survival modeling, mutational and miRNA analysis, gene enrichment, drug prediction, and in vitro assays for cellular behaviors. RESULTS: A total of 83 DEGs were identified in the three datasets, comprising 41 up-regulated genes and 42 down-regulated genes. Utilizing the degree and MCC methods, we identified four hub genes that were hypomethylated and up-regulated: COL1A1, COL1A2, COL3A1, and FN1. Subsequent validation of their expression and promoter methylation on clinical GC samples through targeted bisulfite sequencing and RT-qPCR analysis further confirmed the hypomethylation and overexpression of these genes in local GC patients. Furthermore, it was observed that these hub genes regulate tumor proliferation and metastasis in in vivo and exhibited mutations in GC patients. CONCLUSION: We found four potential diagnostic and prognostic biomarkers, including COL1A1, COL1A2, COL3A1, and FN1 that may be involved in the occurrence and progression of GC.

Deep Learning for Automatic Gross Tumor Volumes Contouring in Esophageal Cancer Based on Contrast-Enhanced Computed Tomography Images: A Multi-Institutional Study.

PURPOSE: To develop and externally validate an automatic artificial intelligence (AI) tool for delineating gross tumor volume (GTV) in patients with esophageal squamous cell carcinoma (ESCC), which can assist in neo-adjuvant or radical radiation therapy treatment planning. METHODS AND MATERIALS: In this multi-institutional study, contrast-enhanced CT images from 580 eligible ESCC patients were retrospectively collected. The GTV contours delineated by 2 experts via consensus were used as ground truth. A 3-dimensional deep learning model was developed for GTV contouring in the training cohort and internally and externally validated in 3 validation cohorts. The AI tool was compared against 12 board-certified experts in 25 patients randomly selected from the external validation cohort to evaluate its assistance in improving contouring performance and reducing variation. Contouring performance was measured using dice similarity coefficient (DSC) and average surface distance. Additionally, our previously established radiomics model for predicting pathologic complete response was used to compare AI-generated and ground truth contours, to assess the potential of the AI contouring tool in radiomics analysis. RESULTS: The AI tool demonstrated good GTV contouring performance in multicenter validation cohorts, with median DSC values of 0.865, 0.876, and 0.866 and median average surface distance values of 0.939, 0.789, and 0.875 mm, respectively. Furthermore, the AI tool significantly improved contouring performance for half of 12 board-certified experts (DSC values, 0.794-0.835 vs 0.856-0.881, P = .003-0.048), reduced the intra- and interobserver variations by 37.4% and 55.2%, respectively, and saved contouring time by 77.6%. In the radiomics analysis, 88.7% of radiomic features from ground truth and AI-generated contours demonstrated stable reproducibility, and similar pathologic complete response prediction performance for these contours (P = .430) was observed. CONCLUSIONS: Our AI contouring tool can improve GTV contouring performance and facilitate radiomics analysis in ESCC patients, which indicates its potential for GTV contouring during radiation therapy treatment planning and radiomics studies.

Concurrent chemoradiotherapy with or without neoadjuvant chemotherapy in pediatric patients with stage III-IVa nasopharyngeal carcinoma: a real-world propensity score-matched cohort study.

OBJECTIVES: To compare neoadjuvant chemotherapy (NAC) plus concurrent chemoradiotherapy (CCRT) to CCRT alone in children and adolescents (age ≤ 18 years) with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC, stage III-IVA). MATERIALS AND METHODS: 195 CA-LANPC patients who were treated through CCRT with or without NAC between 2008 and 2018 were enrolled in this study. A matched cohort composed of CCRT patients and NAC-CCRT patients was generated by propensity score matching (PSM) at a 1:2 ratio. Survival outcomes and toxicities were compared between the CCRT group and NAC-CCRT group. RESULTS: Of the 195 patients, 158 (81%) received NAC plus CCRT, and 37 (19%) received CCRT alone. The NAC-CCRT group had higher EBV DNA levels (≥ 4000 copy/mL), more advanced TNM stage (stage IV disease), and lower incidence of a high radiation dose (> 6600 cGy) than the CCRT group. To avoid bias in treatment selection within retrospectively analysis, 34 patients from the CCRT group were matched with 68 patients from the NAC-CCRT group. In the matched cohort, the 5-year DMFS rate was 94.0% in the NAC-CCRT group versus 82.4% in the CCRT group, with marginal statistical significance (HR = 0.31; 95%CI 0.09-1.10; P = 0.055). During treatment, the accumulate incidence of severe acute toxicities (65.8% vs 45.9%; P = 0.037) in the NAC-CCRT group was higher than the CCRT group. However, the CCRT group had significantly higher accumulate incidence of severe late toxicities (30.3% vs 16.8%; P = 0.041) than the NAC-CCRT group. CONCLUSIONS: Addition of NAC to CCRT tended to improve long-term DMFS in CA-LANPC patients with acceptable toxicity. However, relative randomized clinical trial is still needed in the future.

A pilot study of anlotinib with third-generation epidermal growth factor receptor tyrosine kinase inhibitors in untreated EGFR-mutant patients with advanced non-small cell lung cancer.

Background: In recent years, osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been recommended as a first-line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). A phase III study (AENEAS) to assess the efficacy and safety of aumolertinib, another third-generation EGFR-TKI, vs. gefitinib as a first-line treatment in patients with locally advanced or metastatic NSCLC harboring EGFR mutations has also achieved positive results. Despite the improvements in progression-free survival (PFS) and overall survival (OS) of third- vs. first-generation EGFR-TKIs, combined treatment strategies to postpone drug resistance and further prolong survival benefits remain to be explored. Methods: We conducted a nonrandomized phase II trial (ChiCTR2000035140) of an oral multitarget antiangiogenic TKI (anlotinib) with third-generation EGFR-TKIs (osimertinib or aumolertinib) in untreated patients with EGFR mutation and advanced NSCLC. Anlotinib and the third-generation EGFR-TKIs were orally administrated (anlotinib at a dose of 12 mg once every other day and osimertinib at 80 mg once daily or aumolertinib at 110 mg once daily). The primary end point of the study was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), OS, PFS, and safety of the combined treatment. Results: Enrollment was ceased due to treatment-related adverse events (trAEs) after 11 of 35 planned patients were treated. Among these 11 patients, two were lost to follow-up, and the treatment of five of the remaining nine patients was discontinued due to trAEs, including stomachache, rash, hyponatremia, pulmonary embolism, and interstitial pneumonia. AEs of grade 3 or worse were observed in five patients, but no treatment-related death occurred in these patients. Conclusions: Combining anlotinib and third-generation EGFR-TKIs in untreated EGFR-mutant patients with advanced NSCLC demonstrated significantly increased toxicity, suggesting that the combined treatment strategy was an inappropriate therapeutic choice in this setting.

Targeting the KRT16-vimentin axis for metastasis in lung cancer.

Lung cancer is the most diagnosed malignant cancer and the leading cause of cancer-related deaths worldwide, with advanced stage and metastasis being a major issue. The mechanism leading to metastasis is not yet understood. Here, we found that KRT16 is upregulated in metastatic lung cancer tissues and correlated with poor overall survival. Knockdown of KRT16 inhibits metastasis of lung cancer both in vitro and in vivo. Mechanistically, KRT16 interacts with vimentin, and depletion of KRT16 leads to downregulation of vimentin. KRT16 acquired its oncogenic ability by stabilizing vimentin, and vimentin is required for KRT16-driven metastasis. FBXO21 mediates the polyubiquitination and degradation of KRT16, and vimentin inhibits KRT16 ubiquitination and degradation by impairing its interaction with FBXO21. Significantly, IL-15 inhibits metastasis of lung cancer in a mouse model through upregulation of FBXO21, and the level of IL-15 in circulating serum was significantly higher in nonmetastatic lung cancer patients than in metastatic patients. Our findings indicate that targeting the FBXO21/KRT16/vimentin axis may benefit lung cancer patients with metastasis.

Simultaneous Quantitation of Anlotinib and Osimertinib by Isotope-Labeled UHPLC-MS/MS in Human Plasma: Application in NSCLC Patients.

Anlotinib and osimertinib are a class of tyrosine kinase inhibitors for the treatment of malignant tumor. The combination of anlotinib and osimertinib is currently used for treating non-small cell lung cancer (NSCLC) patients. This study aimed to develop a simple and rapid isotope-labeled UHPLC-MS/MS method for the simultaneous determination of anlotinib and osimertinib in human plasma. The analytes were extracted by protein precipitation with acetonitrile and were then separated on a Shim-pack GIST C18 column. The detection was performed on Shimadzu 8050 triple quadruple mass spectrometer in the positive electrospray ionization mode with multiple reaction monitoring. The precursor-to-product ion transitions were m/z 408.10→ 339.75, 500.25→ 72.20 and 413.50 â†’ 344.50 for anlotinib, osimertinib and D5-anlotinib, respectively. Validation is based on US Food and Drug Administration guidelines. The linearity ranges were 0.5-100 ng/mL for anlotinib and were 1-500 ng/mL for osimertinib with the correlation coefficients (r  2) ≥ 0.99. Accuracy and precision, matrix effect, extraction recovery and stability of anlotinib and osimertinib were acceptable after validation. The UHPLC-MS/MS method was successfully validated and was applied to monitor the concentration of anlotinib and osimertinib in NSCLC patients.

Application of Dynamic 18F-FDG PET/CT for Distinguishing Intrapulmonary Metastases from Synchronous Multiple Primary Lung Cancer.

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted K i value based on dynamic scanning, and corresponding maximum diameter (D max) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SUVmax/D max and K i /D max (ΔSUVmax/D max; ΔK i /D max) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between ΔSUVmax/D max and ΔK i /Dmax from all groups was determined. There was no significant difference for ΔSUVmax/D max between the IPM and sMPLC groups, while the IPM group had a significantly higher ΔK i /Dmax than the sMPLC group. The AUC of ΔK i /D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059, sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91, 95% CI: 0.79-0.96, p < 0.0001) between ΔSUVmax/D max and ΔK i /D max in the IPM group but not in the sMPLC group (Pearson r = 0.45, p > 0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules.

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer.

Background: Evidence of the efficacy of immune checkpoint inhibitors (ICIs) plus antiangiogenic drugs in previously treated patients with advanced non-small-cell lung cancer (NSCLC) is still insufficient, so we investigated the safety and efficacy of nivolumab plus recombinant human (rh)-endostatin in such patients. Methods: Patients without epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) targetable mutations in advanced NSCLC who did not respond to previous treatment were enrolled. Eligible patients received nivolumab (3 mg/kg, i.v. drip, day 1) every 2 weeks and rh-endostatin (210 mg, continuous i.v. infusion for 168 h) every 4 weeks until disease progression or discontinuation. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), clinical benefit response rate (CBR), progression-free survival (PFS), overall survival (OS) and safety. Results: A total of 34 patients received a median of 4 cycles of therapy. In all, 14 patients achieved confirmed partial response (PR) with an ORR of 41.2% [14/34; 95% confidence interval (CI): 23.7-58.6%], DCR of 64.7% (22/34; 95% CI: 47.8-81.6%), CBR of 44.1% (95% CI: 26.5-61.7%), and a DOR of 6.9 (95% CI: 4.4-9.4) months. Median follow-up was 12.2 (range, 2.3-18.1) months. Median PFS (mPFS) was 6.8 (95% CI: 1.1-12.1) months, median OS (mOS) was 17.1 (95% CI: 6.6-27.6) months, and 12-month survival rate of 64.4% (95% CI: 46.2-82.6%). In all, 18 (18/34, 52.9%) patients experienced at least one treatment-related adverse event (TRAE), and Grade 3 TRAEs occurred in 4 (4/34, 11.8%) of them. Conclusions: This study is first to assess nivolumab plus rh-endostatin in previously treated patients with advanced NSCLC. In view of its favorable efficacy and safety profile, this combination represents a promising treatment regimen in this patient population.

Clinical observation of pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) of the lung is a rare type of non-small cell lung cancer (NSCLC), and researches of it are still not enough. METHODS: In this study, we retrospectively analyzed 36 patients with LELC diagnosed in the Fifth Affiliated Hospital of Sun Yat-sen University and Zhaoqing First People's Hospital from January 2014 to June 2021, to investigate the clinical manifestations, tumor markers, treatment, and prognosis of LELC. Clinical data including age, gender, smoking history, family history of cancers, Epstein-Barr virus (EBV) encoding RNA (EBER) status, gene mutations, programmed death-ligand 1 (PD-L1) expression, treatment, and prognosis. RESULTS: There was a total of 36 participants in this study, 16 males and 20 females, the median age was 57 years (37-76 years). A total of 22 cases (61.1%) were advanced (stage III and IV), and EBER was 94.4% positive. Most patients were treated with surgery, platinum chemotherapy, or radiotherapy. At the time of 31 June 2021, 33 participants had survived, and the longest survival time was 72 months. Lung LELC was more common in old participants (≥59 years) and was not associated with smoking history. Expression of PD-L1 was positive in the majority (27 cases, 75%) and participants with positive PD-L1 expression tended to have longer progression-free survival (PFS) and overall survival (OS) time than those with negative PD-L1 expression. CONCLUSIONS: Pulmonary LELC usually occurs in non-smoking patients and is associated with EBV infection. Common treatments for tumors include multimodal therapy. The expression of PD-1 may be related to the prognosis of LELC, but more studies are needed to support further optimization of the treatment of LELC.

Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer.

BACKGROUND: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potential as a biomarker of NSCLC. METHODS: MiR-744 is overexpressed in A549, H460, and H1299 cell lines. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression. A chromatin immunoprecipitation (ChIP) essay was performed to determine the CDX2 binding sites. We then conducted a luciferase reporter essay to analyze interaction between MiR-744 and 3'UTRs (the 3' untranslated sequences). The migration and Boyden chamber method were used to study cell mobility. RESULTS: In this study, we found that ectopic CDX2 increased the expression of miR-744, while the attenuation of CDX2 reduced the expression of miR-744 by qRT-PCR. Chromatin immunoprecipitation experiments confirmed that CDX2 directly binds to the promoter of miR-744. The luciferase reporter assay further verified the binding sites of -347 to -358 bp in the most likely promoter like sequence of miR-744. CDX2-induced up-regulation of miR-744 can significantly promote the migration and invasion of NSCLC cells, while overexpression CDX2 is sufficient to rescue the migration and invasion capacity of these cells following knockdown of miR-744. CONCLUSIONS: In summary, our results confirmed for the first time the regulatory mechanism of CDX2 on miR-744 transcription and provided a potential mechanism for CDX2 as an oncogene in lung cancer.

CRISPR/Cas9 library screening uncovered methylated PKP2 as a critical driver of lung cancer radioresistance by stabilizing ß-catenin.

Radiation resistance is a major cause of lung cancer treatment failure. Armadillo (ARM) superfamily proteins participate in various fundamental cellular processes; however, whether ARM proteins regulate radiation resistance is not fully understood. Here, we used an unbiased CRISPR/Cas9 library screen and identified plakophilin 2 (PKP2), a member of the ARM superfamily of proteins, as a critical driver of radiation resistance in lung cancer. The PKP2 level was significantly higher after radiotherapy than before radiotherapy, and high PKP2 expression after radiotherapy predicted poor overall survival (OS) and postprogression survival (PPS). Mechanistically, mass spectrometry analysis identified that PKP2 was methylated at the arginine site and interacted with protein arginine methyltransferase 1 (PRMT1). Methylation of PKP2 by PRMT1 stabilized ß-catenin by recruiting USP7, further inducing LIG4, a key DNA ligase in nonhomologous end-joining (NHEJ) repair. Concomitantly, PKP2-induced radioresistance depended on facilitating LIG4-mediated NHEJ repair in lung cancer. More strikingly, after exposure to irradiation, treatment with the PRMT1 inhibitor C-7280948 abolished PKP2-induced radioresistance, and C-7280948 is a potential radiosensitizer in lung cancer. In summary, our results demonstrate that targeting the PRMT1/PKP2/ß-catenin/LIG4 pathway is an effective approach to overcome radiation resistance in lung cancer.

The clinical value of bedside ultrasound in predicting the severity of coronavirus disease-19 (COVID-19).

BACKGROUND: To summarise the ultrasound manifestations of coronavirus disease-19 (COVID-19) patients with lung lesions and explore the clinical value of bedside ultrasound in the identification of patients at risk of progression to severe disease. METHODS: This retrospective study enrolled 31 patients with COVID-19 who were admitted to our hospital from January 18 to February 5, 2020. Lung ultrasounds were performed in all cases to evaluate the ultrasound manifestations of the patient's lung lesions and to determine the lung ultrasound scores (LUS). The Cox proportional hazards regression model was used for the multifactor analysis of 7 candidate parameters, including the LUS and the oxygenation index (PaO2/FiO2). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of the LUS. RESULTS: Lung ultrasound images of COVID-19 patients mainly reflected the presence of interstitial pulmonary lesions (90.3%, 28/31). The lung lesions were primarily distributed in the subpleural and peripheral pulmonary zones. Multivariate analyses identified the oxygenation index, the LUS, and the lymphocyte count as factors related to the progression to severe-critical disease in COVID-19 patients (P<0.05). With a cut-off value of 9.5, the area under the ROC curve was 0.910. The LUS showed a sensitivity and specificity of 81.3% and 93.0%, respectively (P≤0.001), with an overall accuracy of 75%. CONCLUSIONS: The lung ultrasound findings in COVID-19 patients were mainly and specifically manifested as interstitial lesions involving the peripheral zones of the lung. In addition, ultrasound imaging could predict the likelihood of COVID-19 patients progressing to severe disease, thereby allowing for early intervention. Thus, lung ultrasounds have great clinical value in monitoring and evaluating COVID-19 patients.

Treatment Patterns and Survival of Patients With Advanced Non-Small Cell Lung Cancer Guided by Comprehensive Genomic Profiling: Real-World Single-Institute Study in China.

Although the National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology guidelines recommend comprehensive genomic profiling of lung adenocarcinoma, it has not been widely applied in Chinese hospitals. This observational study aimed to determine real-world evidence of whether comprehensive genomic profiling can benefit the survival of patients with lung cancer. We investigated the frequency of genomic alterations, treatment strategies, and clinical outcomes in 233 patients with advanced non-small cell lung carcinoma who were routinely screened using a 508-gene panel. The most prevalent drivers were mutations of EGFR (51%), KRAS (9%), PIK3CA (7%), ALK (7%), MET (6%), and BRAF (5%). Mutations in tumor suppressor genes included TP53, KEAP1, RB1, PTEN, and APC. Median overall survival (OS) was significantly shorter among patients harboring KRAS (mutant, n = 17; WT, n = 154) and TP53 (mutant, n = 103; WT n =68) mutations (11.3 vs. 24.0 months; P = 0.16 and 18.7 vs. 28.7 months; P = 0.018, respectively). The OS was longer among patients with tumors harboring EGFR (P = 0.069) and ALK (P = 0.51) mutations. Most patients (65.4%) with the driver gene-positive (EGFR, ALK, and ROS1) tumors were received TKI treatment, whereas those with driver gene wild tumors (53.1%) chose platinum-based therapy. Univariate and multivariate analyses associated a shorter OS among patients with tumors harboring concomitant TP53 and EGFR mutations. These findings provide additional evidence from real-world on the potential importance of targeted therapies as a treatment option in NSCLC patients harboring clinically actionable mutation.

Factors for peripherally inserted central catheters care delay in cancer patients during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. The public health systems have consequently been placed under tremendous pressure. Peripherally inserted central catheters (PICCs) are widely used in patients with cancers. Little is known about the provision of PICCs care amongst cancer patients during this pandemic. METHODS: We studied 156 cancer patients with PICCs treated at the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University between January 2020 and March 2020. Their clinical characteristics, social features, psychological characteristics, and PICCs care situations were analyzed. The chi-squared (χ2) test or Fisher's exact test were used for univariate analyses. Multivariate logistic regression analyses were performed using stepwise variable selection. Differences were evaluated using a two-tailed test, and P<0.05 was considered statistically significant. RESULTS: Of 156 patients, 57 (36.5%) experienced delays of PICCs care, and 12 (21.1%) suffered from complications including infection, thrombosis, and mechanical failure. Univariate analysis detected that the increased risk of PICCs care delay was associated with older age (≥30), lower level of education (<9 years), working, taking public transport to the hospital, anxiety about COVID-19, lower social support rating scale (SSRS) score (<30). Multivariate analysis detected level of education, being employed or not, mode of transport, and SSRS score were independent predictive factors for the delay in PICCs care. CONCLUSIONS: Physical aspects, social factors, and psychological status commonly influenced patients' health care seeking behaviors such as PICCs maintenance. An increase in effort is required from patients' families and society to assure optimal care for cancer patients during this pandemic.

Metformin and oxyphotodynamic therapy as a novel treatment approach for triple-negative breast cancer.

BACKGROUND: Treatment for triple-negative breast cancer (TNBC) remains a significant challenge due to a lack of targeted therapies. While photodynamic therapy (PDT) has been utilized as a treatment approach for several types of cancer, oxyphotodynamic therapy (OPDT) is a novel method that improves treatment efficacy by increasing local oxygen concentration. Metformin (MET) has been demonstrated utility as an anti-tumor agent by acting through the adenosine monophosphate-activated protein kinase (AMPK) pathway. We hypothesized that MET in combination with heme, a byproduct of 5-aminolevulinic acid (ALA), may increase cytotoxicity for cancer treatment. This study aimed to investigate the synergistic effect of MET and ALA with PDT or OPDT on TNBC tumorigenic cells. METHODS: The treatment efficacy and phototoxicity of PDT or OPDT were determined using a cell viability assay. PDT/OPDT experiments were carried out in nine groups based on different combinations and concentrations of ALA and/or MET. To calculate the synergistic effect by compuSyn soft for different groups, cells were incubated with ALA and/or MET at the following concentrations (0, 0.25, 0.5,1, 2, 4, 8, 16, 24, and 32 mM). The fluorescence of ALA-induced protoporphyrin IX (PpIX) and MitoTracker Green were observed under a confocal microscope. RESULTS: The optimized therapeutic concentration ratio of ALA and MET was determined to be 1:1. The inhibition of cancer growth (IC50) for each group was 14.03, 10.62, 7.71, 18.27, 22.09, 23.96, 4.57, 10.20, and 8.18 mM, respectively. The combination index (CI) values (fa =0.5) of the last three combination groups (groups 7, 8, and 9) were 0.44, 1.70, and 1.47, respectively. PpIX fluorescence intensity of group 9 (ALA-MET-OPDT group) remained the highest among all groups, indicating an enhanced therapeutic effect. CONCLUSIONS: This study introduces OPDT as a novel anti-tumor therapy for TNBC. Furthermore, the combined use of ALA and MET had a synergistic anti-tumor effect in TNBC cells when combined with OPDT.

Clinical observation of Pemetrexed first-line treatment in advanced non-squamous lung cancer or non-small cell lung cancer without driver-mutations: a phase 2, single-arm trial.

BACKGROUND: Non-dominant population, which means patients with advanced non-squamous lung cancer or non-small cell lung cancer (NSCLC) without driver-mutations, who are excluded from clinical studies because of specific baseline conditions refractory to multiple treatments, have poor outcomes. We assessed the activity of pemetrexed first-line treatment for a non-dominant population, explore the safety and efficacy of pemetrexed therapy. METHODS: We did this two-phased, single-arm trial at two sites at the Fifth Affiliated Hospital of Sun Yat-sen University and Guangxi medical university cancer hospital. Pemetrexed 500 mg/m2, static drops on day 1; 21 days for a cycle, each treatment for at least two cycles and up to six cycles. Efficacy was assessed every two cycles. RESULTS: We counted the July 21, 2018 to 2020 on May 31, first diagnosed with IIIb-IV period (American Joint Committee on Cancer eighth edition) no drive genes, non-squamous cell carcinomas, 30 patients with non-small cell lung cancer, the follow-up to July 31, 2020, median follow-up time was 12 months. Most were elderly patients with poor general conditions (96.7% of patients had ECOG scores of 2-3) (median age 66 years). Median duration of maintenance treatment was 6 months. Median progression-free survival was 6.5 months. Median overall survival was 12 months. Patients with performance status =0-2 had a significantly higher median overall survival time (16 months) compared with patients with performance status =3 who had a median overall survival time of 7 months (P=0.001). Most treatment-related adverse events were grade 1 or grade 2. CONCLUSIONS: This study is the first to investigate the survival benefit and toxicity tolerance of pemetrexed treatment in non-dominant population in the real world, providing a new therapeutic possibility for those who failed to be enrolled in clinical studies.

The impact of the COVID-19 pandemic on lung cancer patients.

BACKGROUND: The coronavirus disease (COVID-19) poses an unprecedented challenge to health and epidemic prevention system, especially the healthcare of patients with cancer. We sought to study the impact of COVID-19 on lung cancer patients in our center. METHODS: We initiated a retrospectively study to analyze the impact of COVID-19 on lung cancer patients in our center, who were accepted for routine anticancer treatment before the epidemic and planned to return to hospital in January and February of 2020. RESULTS: A total of 161 cases of lung cancer were included in the final analysis. As of April 15, 95 patients had delayed their return visit, and 47 cases were finally designated as having delayed admission during the epidemic and having to discontinue or delay their regular anticancer treatments. Of these 47 delayed patients, 33 were evaluated for tumor status using a computed tomography scan, 6 of these 33 cases (18.18%) were diagnosed as progressive disease (PD), and 5 cases did not return for visit. CONCLUSIONS: This is the first study investigating impact of COVID-19 on non-COVID-19 lung cancer patients during the pandemic. The study demonstrates the significant impact of the COVID-19 crisis on oncological care, indicating the need for appropriate change of treatment decisions and continued follow-up and psycho-oncological support during this pandemic.

CD47 Overexpression Is Associated with Epstein-Barr Virus Infection and Poor Prognosis in Patients with Nasopharyngeal Carcinoma.

PURPOSE: Little is known about the clinical significance of CD47 expression and its association with Epstein-Barr virus (EBV) infection in patients with nasopharyngeal carcinoma (NPC). The aim of this study was to clarify the prognostic value and role of CD47 in EBV-associated NPC. MATERIALS AND METHODS: Sixty-six cases of non-metastatic NPC were retrospectively reviewed. Tissues were collected for immunohistochemical staining of CD47 and the EBV-encoded oncoprotein latent membrane protein 1 (LMP1). Western blotting and quantitative real-time PCR were performed to determine the CD47 and LMP1 levels in common human NPC cell lines. Additionally, CD47 and LMP1 expression in a constructed EBV-positive human NPC cell (CNE-2-EBV+) and a stable cell line transfected with LMP1 plasmid (CNE-2-LMP1) was assessed. Next, we used Western blotting to assess the decrease in CD47 expression on CNE-2-LMP1 cells after transfecting them with small interfering RNA (siRNA)-targeting LMP1. RESULTS: In NPC patients, CD47 overexpression was significantly associated with disease recurrence (P=0.010), leading to poorer disease-free survival (DFS; P=0.002) and overall survival (P=0.021). Multivariate Cox proportional hazards models demonstrated that CD47 (HR=5.452, P=0.016) was an independent prognostic factor of DFS. Moreover, CD47 expression was associated with plasma EBV-DNA copy number and LMP1 tissue expression. Among the human NPC cell lines, CD47 and LMP1 expression was notably higher in the EBV-positive C666-1 cell line than in the EBV-negative cell lines. Furthermore, EBV infection upregulated CD47 expression via LMP1-mediated pathways in human NPC cells. CONCLUSION: This study indicated that CD47 is related to EBV infection in NPC patients, and it is a feasible biomarker.

High expression of IGBP1 correlates with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Immunoglobulin binding protein 1 (IGBP1) is an important signal transduction regulator that mediates various functions. However, its expression profile, role, and clinical significance in cancers are uncertain. The purpose of this study was to determine the expression profile and the prognostic significance of IGBP1 in esophageal squamous cell carcinoma (ESCC). METHODS: Polymerase chain reaction assay, western blotting, and immunohistochemistry (IHC) assay were performed to examine IGBP1 expression in ESCC tissues and matched adjacent non-cancerous tissues. Moreover, IHC was used to evaluate IGBP1 expression in archived 190 paraffin-embedded ESCC specimens. Statistical analyses were applied to evaluate the prognostic value and the correlations between IGBP1 expression and the clinical parameters. RESULTS: We found that the messenger RNA and protein levels of IGBP1 were up-regulated in the ESCC tissues compared with their adjacent non-cancerous tissues. High expression of IGBP1 in ESCC patients was positively associated with T classification (P=0.013) and vital status (P=0.03). The ESCC patients with higher IGBP1expression had a shorter survival time than those with lower IGBP1 expression. Importantly, multivariate analysis demonstrated that the expression of IGBP1 was an independent prognostic factor for ESCC (P< 0.05). CONCLUSIONS: We provide the first evidence that increased IGBP1 expression correlates with poor prognosis of ESCC, and that IGBP1 may be a tumor promoter of ESCC, which provide a promising prognostic biomarker and therapeutic target for ESCC.

Expression and clinical significance of PD-L1 and c-Myc in non-small cell lung cancer.

BACKGROUND: It is known that there are insufficient prognostic factors for non-small cell lung cancer (NSCLC). It was reported that PD-L1 was a prognostic factor for NSCLC,and c-Myc regulated the expression of PD-L1. Herein, we investigated c-Myc and PD-L1 expression and their association with overall survival (OS) in NSCLC. METHODS: Formalin-fixed paraffin-embedded specimens were obtained from 128 patients with surgically resected primary NSCLC. Immunohistochemistry was used to assess the expression of PD-L1 and c-Myc in this study. Pearson's Chi squared test or Fisher's exact test was used to analyze the correlation of the expression of PD-L1 and c-Myc with clinicopathologic features. The relationship between OS and the expression of PD-L1 and c-Myc was evaluated by the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Positive expression of PD-L1 was detected in 59 patients (46.1%). Patients with negative expression of PD-L1 had remarkably longer OS than those with positive expression of PD-L1. The positive expression rate of c-Myc in NSCLC accounted for 58.6% (75/128) and its expression was significantly more frequent in males (p = 0.002) and patients with lymph node metastasis (p = 0.029). PD-L1 expression was positively correlated with c-Myc expression (r = 0.459, p < 0.001). The PD-L1 and c-Myc double-positive group had a worse prognosis than other subgroups (p < 0.05), and the PD-L1 and c-Myc double-negative group had a better OS than other subgroups (p < 0.05). CONCLUSION: Conjoint analysis of the expression of PD-L1 and c-Myc was a better prognostic approach for NSCLC patients.