Asynchrony of primary tumor and mediastinal lymph nodes response after neoadjuvant immunotherapy plus chemotherapy in a patient with stage IIIA non-small-cell lung cancer: a case report.

With the rapid development of immunotherapy, the efficacy and feasibility of neoadjuvant immunotherapy for early resectable non-small-cell lung cancer (NSCLC) has been demonstrated. However, there are still difficulties and controversies in evaluating the efficacy of neoadjuvant immunotherapy. In our report, we described a 43-year-old female patient who was diagnosed with stage IIIA (cT1N2M0) pulmonary adenocarcinoma. After two cycles of neoadjuvant immunotherapy (sintilimab) combined with chemotherapy, according to imaging evaluation, the efficacy of the primary lesion was evaluated as stable disease and the mediastinal lymph nodes were evaluated as partial response. However, the postoperative pathological evaluation showed the primary lesion was pathological complete response and the mediastinal lymph nodes were major pathological response. This indicated that neoadjuvant chemo-immunotherapy was effective for both primary and mediastinal lymph nodes, but regression of the lesions was not synchronous. This study provided a complete process of neoadjuvant treatment, illustrating the effectiveness and safety of neoadjuvant chemo-immunotherapy to a certain extent. It is also suggested that the evaluation of neoadjuvant immunotherapy should be combined with imaging and pathology, and the primary tumor and lymph nodes should be evaluated, respectively.

Successful treatment of Afatinib plus Apatinib using for a lung adenocarcinoma patient with HER-2 V659D mutation: a rare case report.

Lung cancer is one of the most important and lethal cancers in the world. Human epidermal growth factor 2 (HER2) is a member of the erbB receptor tyrosine kinase family. The incidence of HER2 kinase domain mutations in adenocarcinoma of lung ranges from 1% to 3%. HER2 V659D mutation is located in the trans-membrane domain (TMD) with only a few cases reported before, and importantly, there were no more standard and effective ways for this kind of diseases until now. Afatinib irreversibly blocks all kinase-competent HER family members. Apatinib is one of the small-molecule oral anti-angiogenesis-targeted agents developed firstly in China, and it's a highly selective inhibition of the activity of VEGFR-2. This report presents an advanced lung adenocarcinoma patient with HER2 V659D mutation who was treated with combination of Afatinib and Apatinib. He achieved good efficacy and tolerable adverse reactions.

Formononetin alleviates Streptococcus suis infection by targeting suilysin.

Streptococcus suis serotype 2 (SS2) has become a leading pathogen responsible for swine industry and human infections, causing enormous economic loss and triggering food safety risk. New and alternative strategies for combating this microorganism are urgently needed. Suilysin (SLY), a pore-forming toxins produced by SS2 has been revealed play critical role during its infection and could be an ideal target for combating this pathogen. Here, we found that formononetin (Form) inhibited the haemolytic activity of SLY without exerting growth pressure on SS2 or affecting the expression of SLY. At the cellular infection level, Form treatment diminished the cytotoxicity induced by SLY or SS2 and inflammatory response induced by SS2. In addition, the treatment with Form reduced bacterial burden in livers and spleens in SS2 infected mice. These data revealed that Form could attenuate the pathogenesis of SS2 both in vitro and in vivo by targeting SLY, suggesting that this compound could be used in combating S. suis infections.

Metallothionein induction attenuates the progression of lung injury in mice exposed to long-term intermittent hypoxia.

BACKGROUND: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is prevalent in older adults and associated with inflammation. We previously showed that IH induces renal fibrosis and cardiomyopathy and hypothesized that lung inflammatory changes may underlie deficits in pulmonary function in OSA. METHODS: Pulmonary inflammatory and oxidative markers were assessed in metallothionein KO (MT-KO) mice and WT 129S1 controls exposed to IH or to normoxia for 8 weeks. RESULTS: MT expression increased at 3 days in WT, falling back at 1 week. Pro-fibrotic markers CTGF and PAI-1 were unchanged in WT, but increased at 3 or 8 weeks, with enhanced Sirius Red staining at 8 weeks, in IH-exposed MT-KO. Cellular infiltration, TNF-α and IL-6 increased earlier in IH-exposed MT-KO than in WT. Oxidative markers, 3-nitrotyrosine and 4-hydroxynonenal increased in both but persisted in MT-KO. Antioxidant Nrf2, HO-1 and NQO1, increased at 3 days in WT mice and at 8 weeks IH in MT-KO. While early Nrf2 induction required MT, its later increase at 8 weeks in MT-KO was independent from MT. CONCLUSIONS: We conclude that early MT and antioxidant gene response protects from fibrotic changes in long-term IH-exposed mouse lung. Without this response, pulmonary fibrosis may develop with longer IH exposure.

Inhibition of protein kinase CK2 sensitizes non-small cell lung cancer cells to cisplatin via upregulation of PML.

Non-small cell lung carcinoma (NSCLC), a malignancy of lungs, is very aggressive and usually ends up with a dismal prognosis. Cisplatin (CDDP)-based systemic chemotherapy is the main pharmaceutical approach for treating NSCLC, but its effect is discounted by some hitherto unknown reasons. Thus, this study is dedicated to improving the efficacy of CDDP. Our results show that combining use of CDDP with CK2 siRNA or inhibitor is more efficient in suppressing cancer cell growth and promoting apoptosis than use of CDDP alone. The underlying mechanism is that CDDP has two pathways to go: one is that it directly induces apoptosis and the other is that it activates CK2, which suppresses proapoptosis gene promyelocytic leukemia (PML). In conclusion, inhibiting CK2 can enhance sensitivity of CDDP to NSCLC cancer cells through PML.

[Efficacy of adjuvant therapy in 110 patients with N1 lymph node metastasis of esophageal squamous cell carcinoma].

OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant therapy on the survival in patients with N1 lymph node metastasis of esophageal squamous cell carcinoma (ESCC). METHODS: 110 patients with positive N1 lymph node metastasis of esophageal squamous carcinoma were included in this study. The surgery group included 46 cases and the postoperative adjuvant therapy group included 64 cases (24 cases in the adjuvant chemotherapy subgroup and 40 cases in the adjuvant concurrent chemoradiotherapy). The disease-free survival (DFS) and overall survival (OS) of the two groups were compared and the prognostic factors were analyzed by multivariate Cox model. RESULTS: In the postoperative adjuvant therapy group, the DFS (16.8 months) and OS (21.3 months) were significantly prolonged compared with those in the surgery group (10.6 months, P=0.007) and (13.7 months, P=0.001), respectively. Postoperative adjuvant chemotherapy significantly extended the OS (31.1 months) of N1-positive patients compared with 13.7 months (P=0.002) in the surgery group. But there were no significant differences between the DFS in the two subgroups (16.3 and 16.8 months, P=0.346) and between the OS (23.4 and 21.3 months, P=0.491). Postoperative adjuvant therapy was an independent prognostic factor in the ESCC patients with N1 lymph node metastasis. CONCLUSION: Postoperative adjuvant therapy can improve the prognosis and prolong the survival time in ESCC patients with positive N1 lymph node metastasis.

An intraventricular meningioma and recurrent astrocytoma collision tumor: a case report and literature review.

BACKGROUND: Intracranial meningioma and glioma collision tumors are relatively uncommon and are even more rarely located within the ventricles. CASE PRESENTATION: Here, we report a case of a patient with an intraventricular meningioma and astrocytoma collision tumor. A 39-year-old man previously underwent excision of an astrocytoma in the triangle area of the lateral ventricle and exhibited good post-surgery recovery. The astrocytoma recurred in situ six years after the surgery, and the case was complicated by a malignant meningioma. The patient recovered well after surgery to treat the recurrence and was administered radiotherapy after discharge. In addition to reporting on this case, we conducted a literature review of collision tumors; based on this review, we propose several hypotheses regarding the formation of collision tumors. CONCLUSIONS: We conclude that a possible cause of the collision tumor formation between the intracranial meningioma and the astrocytoma was the recurrence of an astrocytoma-induced malignancy of the arachnoid cells in the choroid plexus.

[Relationship between the efficacy of gemcitabine/cisplatin adjuvant chemotherapy and RRM1 protein expression in postoperative NSCLC patients].

OBJECTIVE: The purpose of this study was to investigate the relationship between the expression of ribonucleotide reductase subunit M1 (RRM1) protein and the efficacy of gemcitabine/cisplatin (GP) adjuvant chemotherapy in postoperative non-small cell lung cancer (NSCLC) patients. METHODS: A total of 68 patients with NSCLC after radical surgery were included in this study. The expression of RRM1 protein in tumor specimens was assayed by streptavidin-peroxidase (SP) immunohistochemistry retrospectively. Correlation between the expression of RRM1 protein and the efficacy of GP chemotherapy was analyzed. Disease-free survival rate was taken as the main outcome measure. RESULTS: Among the 68 patients, 31 cases had recurrence or metastasis. The expression rate of RRM1 was 54.4%. The 1-year and 3-year disease-free survival rates were 82.7% and 61.5% for patients with RRM1-negative expression, and 78.1% and 36.8% for patients with RRM1-posivive expression, respectively (P = 0.044). In the subgroup analysis of stage IB cases, the 1-year and 3-year disease-free survival rates were 100% and 82.3% for patients with RRM1-negative expression, and 84.5% and 24.6% for patients with RRM1-positive expression, respectively (P = 0.047). In the analysis of squamous cell carcinoma subgroup, the 1-year and 3-year disease-free survival rates were 92.3% and 83.7% for patients with RRM1-negative expression, and 83.1% and 43.9% for patients with RRM1-posivive expression, respectively (P = 0.005). Univariate analysis and multivariate analysis indicated that smoking history, pathological type, clinical stage and expression of RRM1 significantly influenced the therapeutic efficacy (P < 0.05). CONCLUSIONS: RRM1 protein may be a valuable predictive factor for gemcitabine/cisplatin adjuvant chemotherapy in NSCLC patients.

Efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy in potentially resectable stage IIIA/IIIB non-small cell lung cancer: Neo-Pre-IC, a single-arm phase 2 trial.

Background: Some locally advanced (IIIA/IIIB) non-small cell lung cancers (NSCLCs) might have surgical options available. However, information regarding the effectiveness of neoadjuvant immunotherapy for potentially resectable IIIA/IIIB NSCLC is limited. The intent of this investigation was to offer a more favourable alternative to the standard approach of chemoradiotherapy (concurrent or sequential chemoradiotherapy) followed by immunotherapy for potentially resectable stage III NSCLC. Methods: This prospective, single-arm, phase 2 clinical trial (NCT04326153) enrolled treatment-naïve patients with 'potentially resectable' IIIA/IIIB NSCLC who were deemed unsuitable for complete (R0) resection upon initial diagnosis. The study period was between March 20, 2020, and August 20, 2021. Patients underwent neoadjuvant chemoimmunotherapy (sintilimab combined with nab-paclitaxel and carboplatin) for two to three cycles prior to surgical resection of the lung carcinoma and systematic nodal dissection within 30-45 days. The primary endpoint was the 2-year disease-free survival (DFS) rate, with secondary endpoints encompassing major pathological response (MPR) rate, pathological complete response (pCR) rate, overall survival, objective response rate (ORR), downstaging rate, and adverse events (AEs). Tumour immune cell infiltrates, identified via immunohistochemistry, were assessed as biomarkers at baseline and after surgery. Findings: Among 30 patients who received neoadjuvant chemoimmunotherapy, 20 underwent complete resection. The disease control rate was 96.7% (95% CI: 90.3%-99.99%), with an ORR of 55% (95% CI: 37.2%-72.8%) and a downstaging rate of 80% (95% CI: 65.7%-94.3%). In the subgroup of 20 patients who underwent surgery, the MPR rate was 65% (95% CI: 43.3%-82.9%), and the pCR rate was 40% (95% CI: 21.2%-46.3%). The 2-year DFS rate in the surgical group was 75% (95% CI 56%-94%). Notably, the MPR group demonstrated significantly prolonged DFS compared with the non-MPR group (p = 0.00024). A significant increase in pretreatment CD8 expression correlated with improved DFS (p = 0.00019). Three patients (10%) experienced grade 3 or higher immune-related AEs-one case of grade 3 elevated myocardial enzymes, one case of grade 3 interstitial pneumonia, and one case of grade 5 bronchopleural fistula. Interpretation: Neoadjuvant immunotherapy markedly enhanced the rate of pathological response and 2-year DFS in patients with potentially resectable IIIA/IIIB NSCLC. Overexpression of CD8 before treatment (H score≥3) may serve as a potential predictive biomarker for DFS. Consequently, the treatment landscape for potentially resectable IIIA/IIIB NSCLC could undergo changes. Funding: This study did not receive any financial support.

[Retracted] miR­154 suppresses non­small cell lung cancer growth in vitro and in vivo.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 5 were strikingly similar to data appearing in different form in other articles by different authors, some of which have been retracted. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 33: 3053­3060, 2015; DOI: 10.3892/or.2015.3895].

Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage IIIA/IIIB non-small cell lung cancer: a single-arm, phase 2 trial.

INTRODUCTION: While some clinical studies have shown that PD-1 and PD-L1 can also be an effective neoadjuvant treatment for early-stage non-small cell lung cancer (NSCLC), no evidence has been available for the use of the PD-1 inhibitor sintilimab combined with chemotherapy as a neoadjuvant treatment for potentially resectable NSCLC in the Chinese population. METHODS: This prospective, single-center, single-arm, phase 2 clinical trial (registration number: NCT04326153) included treatment-naive patients with potentially resectable NSCLC (stage IIIA/IIIB) who received sintilimab plus nab-paclitaxel and carboplatin for two to three cycles before systematic nodal dissection 30 to 45 days after neoadjuvant treatment. After surgery, patients needed to complete two cycles of adjuvant chemoimmunotherapy (sintilimab + nab-paclitaxel + carboplatin). The primary endpoint was disease-free survival rate at 24 months, whereas secondary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, the proportion of patients who achieved tumor downstaging, overall survival, objective response rate (ORR), and adverse effects. PD-L1 status before and after treatment was also determined. RESULTS: Among the 20 patients who received neoadjuvant chemoimmunotherapy, 16 underwent radical resection. The disease control rate and ORR were 90% and 70%, respectively. Among the 16 patients who underwent surgery, 10 (62.5%) and 5 (31.25%) achieved MPR and pCR, respectively. Squamous cell NSCLC exhibited superior response rates compared to adenocarcinoma (pCR 35.7% vs. 0%). Moreover, 14 patients (70%) experienced grade 1 or 2 neoadjuvant treatment-related adverse events (TRAEs), whereas 6 (30%) experienced grade 3 TRAEs. Bronchopleural fistula (BPF) was found in the current study as an adverse reaction of concern. The rate of BPF was 20% (4/20), of which three patients were in grade 1-2, and one patient died. The occurrence of BPF had no significant correlation with basic disease history, nutritional status, anemia, hypoalbuminemia, surgical procedure, pathological remission, and PD-L1 expression. However, during neoadjuvant treatment, no adverse events prompted dose reduction, treatment discontinuation, surgery delay, or death. Although PD-L1 expression may change after chemoimmunotherapy, no regular pattern was noted. PD-L1 expression, neither at baseline nor after neoadjuvant chemoimmunotherapy, was associated with pathological remission. CONCLUSIONS: The current study found similar ORR, slightly lower MPR and pCR rates, and lower grade 3 TRAEs among patients with potentially resectable stage IIIA/IIIB NSCLC compared to the NADIM trial, as well as a greater ORR, MPR rate, pCR rate, and grade 3 TRAEs compared to Gao's study involving sintilimab for Chinese patients with resectable stage IA-IIIB NSCLC. Though neoadjuvant chemoimmunotherapy had been found to promote a high risk of BPF for patients with stage IIIA/IIIB disease, it offered greater potential for radical cure. Therefore, the current study suggests that neoadjuvant chemoimmunotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.

Inhalation of alcohol vapor driven by oxygen is a useful therapeutic method for postoperative alcohol withdrawal syndrome in a patient with esophageal cancer: a case report.

A 65-year-old man suffering from esophageal cancer presented with postoperative alcohol withdrawal syndrome. Diazepam was used intravenously, but his condition did not improve. With inhalation of alcohol vapor driven by oxygen, the abnormal symptoms subsided and vital signs began to return to normal rapidly. This method is also beneficial for expectoration and redressing hypoxemia.

miR-154 inhibits migration and invasion of human non-small cell lung cancer by targeting ZEB2.

[This retracts the article DOI: 10.3892/ol.2016.4577.].

Erratum: MiR-338-3p inhibits the growth and invasion of non-small cell lung cancer cells by targeting IRS2.

[This corrects the article on p. 53 in vol. 7, PMID: 28123847.].

Interferon regulatory factor 6 correlates with the progression of non-small cell lung cancer and can be regulated by miR-320.

OBJECTIVES: The expression of interferon regulatory factor 6 (IRF6) has been reported in several cancer types, but its roles underlying the progression of lung cancer have not been detailedly investigated. METHODS: The pairs of lung cancer tissues and para-carcinoma tissues and The Cancer Genome Atlas database were collected to detect IRF6 expression. Cell counting kit-8, transwell and terminal-deoxynucleoitidyl transferase-mediated nick end labelling assays were used to evaluate cell proliferation, migration and apoptosis. KEY FINDINGS: A significant up-regulation of IRF6 in both lung adenocarcinoma and lung squamous cell carcinoma tissues compared with normal non-tumor tissues. Subsequently, Immunostaining also revealed that canceration of lung tissues predisposed to evoke IRF6 expression. In vitro experiments revealed the antitumour effects, including growth and migration inhibition, of IRF6 siRNA transfection. Considering miR-320 as an endogenous inhibitor to IRF6, miR-320 mimics transfection led to the inhibition of proliferation and migration of lung cancer cells. However, overexpressed IRF6 neutralized the antineoplastic activities of miR-320 in lung cancer cells. CONCLUSIONS: The miR-320/IRF6 signalling axis was implicated in pulmonary canceration. miR-320 as an endogenous inhibitor of IRF6 provided a novel therapeutic strategy for the treatment of lung cancer.

Coexistence of atypical adenomatous hyperplasia, minimally invasive adenocarcinoma and invasive adenocarcinoma: Gene mutation analysis.

Multiple primary lung cancer (MPLC) refers to the simultaneous occurrence of two or more lung primary malignant tumors in one individual. The detection rate of MPLC has increased significantly in recent years, and the distinction between MPLC and lung metastasis has strong clinical significance. Whole exome sequencing (WES) can clearly identify the heterogeneity between MPLC nodules. Here, we report a case of a 50-year-old Asian female without a history of smoking. She underwent a lung computed tomography (CT) scan and three ground-glass nodules (GGNs) were found which were pathologically confirmed as atypical adenomatous hyperplasia (AAH), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA), respectively. We performed WES on the three pulmonary nodules and analyzed the sequencing results. We believe that this is the first published report of a case of "three phases" of lung adenocarcinoma analyzed by WES. Under the same genetic background and internal environment, these three nodules showed significant genetic differences and developed into "three phases" of lung adenocarcinoma. Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We used WES to analyze the gene mutation status of three tumors in one individual. We found that even if under the same genetic background, AAH, MIA and IA showed significant genetic differences and developed into "three phases" of lung adenocarcinoma. WHAT THIS STUDY ADDS: Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets.

Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial.

BACKGROUND: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. METHODS: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797. FINDINGS: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group. INTERPRETATION: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. FUNDING: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Long non-coding RNA LINC00525 promotes the non-small cell lung cancer progression by targeting miR-338-3p/IRS2 axis.

Long non-coding RNA LINC00525 has been reported to be upregulated in non-small cell lung cancer (NSCLC), however, its biological roles and underlying mechanism involved in modulation of NSCLC remain largely unclear. Real-time PCR were performed to determine the expression of LINC00525 and miR-338-3p in NSCLC tissues and cell lines. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and colony-formation assays. Cell migration and invasion were determined by wound healing and transwell invasion assays, respectively. Luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to detect the interactions between molecules. The protein expression was measured by Western blot. Xenograft tumor was established to determine the effect of LINC00525 on NSCLC growth in vivo. LINC00525 expression was significantly upregualted in NSCLC tissues and cell lines, and correlated with poor prognosis. LINC00525 depletion inhibited the proliferation, migration and invasion in NSCLC cell line A549 and SPC-A1 cells. In vivo study further confirmed that LINC00525 knockdown inhibited tumor growth in nude model. Mechanically, LINC00525 served as a molecular sponge for miR-338-3p, and modulated expression of endogenous miR-338-3p-targeted insulin receptor substrate 2(IRS2). These findings indicated that LINC00525 might be the potential target for NSCLC treatment.

Chemovirotherapy of Lung Squamous Cell Carcinoma by Combining Oncolytic Adenovirus With Gemcitabine.

Oncolytic virotherapy is emerging as an important agent in cancer treatment. In a previous study, we designed and constructed Ad-Apoptin-hTERTp-E1a (Ad-VT), a dual cancer-selective anti-tumor recombinant adenovirus. In this study, crystal violet staining and WST-1 assays showed that Ad-VT has a significant tumor killing effect in a time and dose dependent manner. The combination of Ad-VT (10 MOI) and gemcitabine (10 nM) significantly inhibited NCI-H226 cells, but did not increase the killing effect of gemcitabine on human normal bronchial epithelial cells BEAS-2B. Hoechst, JC-1 and Annexin V experiments demonstrated that the combination of Ad-VT and gemcitabine mainly inhibited NCI-H226 cell proliferation by inducing apoptosis (mitochondrial pathway). The combination also significantly inhibited the migration and invasion abilities of NCI-H226 cells. In vivo, Ad-VT in combination with low-dose gemcitabine could effectively inhibit tumor growth and prolong survival of mice. Ad-VT has the characteristics of tumor-selective replication and killing, in vitro and in vivo. The combined application of Ad-VT and gemcitabine has a synergistic effect, which can increase the anti-tumor effect and reduce the toxicity of chemotherapy drugs, indicating that Ad-VT has a potential clinical value in the treatment of lung squamous cell carcinoma.

Aggravation of depigmentation for a non-small-cell lung cancer patient with pre-existing vitiligo using anti-programmed cell death-1 therapy: case report.

Immune checkpoint inhibitors can enhance the antitumor activity of the immune system by mainly promoting CD8+ T lymphocyte immune function. However, they can also induce immune-related adverse events, especially skin toxicity. Some studies found that patients with autoimmune or inflammatory disease are susceptible to immune checkpoint inhibitors and were associated with a significantly increased risk of immune-related adverse events. In our present report, we described a newly diagnosed non-small-cell lung cancer patient who suffered from focal vitiligo for approximately ten years and was treated with the anti-programmed cell death-1 receptor antibody camrelizumab (SHR-1210), which accelerated the aggravation of depigmentation of the skin over the whole body in just half a year.