Background: The coronavirus disease 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.

Background: Small cell lung cancer (SCLC) is the most deadly and aggressive type of primary lung cancer, with the 5-year survival rate lower than 5%. The FDA has approved arsenic trioxide (As 2 O 3 ) for acute promyelocytic leukemia (APL) treatment. However, its role in SCLC-derived cancer stem cells (CSCs) remains largely unknown.Methods: CSCs were enriched from SCLC cell lines by culturing them as spheres in conditioned serumfree medium. Then, qPCR, western blot, serial passage, limiting dilution, Transwell, and tumorigenesis assay were performed to verify the cells' stem phenotypic characteristics. Anticancer efficiency of As 2 O 3 was assessed in these cells using CCK8, colony formation, sphere formation, flow cytometry, qPCR, western blot analysis in vitro, and tumor growth curve, immunofluorescence, and TUNEL staining analyses in vivo.Results: The fifth-passage SCLC spheres showed a potent self-renewal capacity, higher clonal formation efficiency (CFE), SOX2, c-Myc, NANOG, and OCT4 levels, and invasion ability, and stronger tumorigenesis capacity than the parental SCLC cells, indicating that the SCLC sphere cells displayed CSC features. As 2 O 3 inhibited the proliferation, clonality and sphere forming ability of SCLC-derived CSCs and suppressed the tumor growth of CSCs-derived xenograft tumors. As 2 O 3 induced apoptosis and downregulation of SOX2 and c-Myc in vitro and in xenografts. Besides, SOX2 knockdown suppressed SCLC-derived CSCs to selfrenew and induced apoptosis. Mechanistically, expression of GLI1 (a key transcription factor of Hedgehog pathway) and its downstream genes increased in SCLC-derived CSCs, compared to the parental cells. As 2 O 3 dramatically downregulated GLI1 and its downstream genes in vitro and in vivo. The GLI inhibitor (GANT-61) recapitulated and enhanced the effects of As 2 O 3 on SCLC-derived CSCs, including growth suppression, apoptosis induction, and GLI1, SOX2 and c-Myc downregulation. Conclusions: Altogether, As 2 O 3 effectively suppressed SCLC-derived CSCs growth by downregulating stem cell-maintenance factors and inducing apoptosis. These effects are mediated at least partly via the Hedgehog signaling blockade.

Abstract. Arsenic trioxide (As 2 O 3 ) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As 2 O 3 on lung cancer and explored its possible mechanism. It was observed that As 2 O 3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As 2 O 3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As 2 O 3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-β, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As 2 O 3 . These findings suggested that anti-angiogenesis may be an underlying mechanism of As 2 O 3 anticancer activity in lung cancer.

Small-cell lung cancer (SCLC) is a highly malignant type of lung cancer with no effective second-line chemotherapy drugs. Arsenic trioxide (As2O3) was reported to exert antiangiogenesis activities against lung cancer and induce poor development of vessel structures, similar to the effect observed following the blockade of Notch signaling. However, there are no direct evidences on the inhibitory effects of As2O3 on tumor growth and angiogenesis via blockade of Notch signaling in SCLC. Here, we found that As2O3 significantly inhibited the tumor growth and angiogenesis in SCLC and reduced the microvessel density. As2O3 disturbed the morphological development of tumor vessels and downregulated the protein levels of delta-like canonical Notch ligand 4 (Dll4), Notch1, and Hes1 in vivo. DAPT, a Notch signaling inhibitor, exerted similar effects in SCLC. We found that both As2O3 treatment and Notch1 expression knockdown resulted in the interruption of tube formation by human umbilical vein endothelial cells (HUVECs) on Matrigel. As2O3 had no effects on Dll4 level in HUVECs but significantly inhibited the expression of Notch1 and its downstream gene Hes1 regardless of Dll4 overexpression or Notch1 knockdown. These findings suggest that the antitumor activity of As2O3 in SCLC was mediated via its antiangiogenic effect through the blockade of Notch signaling, probably owing to Notch1 targeting.

Background The inhibitory effect of arsenic trioxide (As 2 O 3 ) on lung cancer has been reported in some preclinical studies. However, its effect on small cell lung cancer (SCLC) has been poorly explored. Calcineurin and its substrate, nuclear factor of activated T cells (NFAT), mediate the downstream signaling of VEGF, and is critical in the process endothelium activation and tumor metastasis. In this study, we aimed to evaluate whether As 2 O 3 had inhibitory effects on endothelial cells activation and the metastasis of SCLC, and to explore the possible mechanisms. Material/Methods In vitro , human umbilical vein endothelial cells (HUVECs) were used. Cell Counting Kit-8 assay and cell migration assay were performed to determine the effect of As 2 O 3 on HUVECs proliferation and migration. The level of calcineurin, NFAT, downstream factors for Down syndrome candidate region 1 (DSCR1), and the endogenous inhibitor of calcineurin, were evaluated by quantitative PCR and western blotting. In vivo , SCLC metastasis models were established by injecting NCI-H446 cells into tail veins of nude mice. Tumor-bearing mice were treated with As 2 O 3 or calcineurin inhibitor for 10 days, after which tumor metastasis in target organs was evaluated. Results As 2 O 3 significantly inhibited the proliferation and migration of endothelial cells. Also, As 2 O 3 inhibited the expression levels of calcineurin, NFAT, and the downstream target genes CXCR7 and RND1, while it upregulated the level of DSCR1. Both As 2 O 3 and calcineurin inhibitor exhibited notable inhibitory effect on the metastasis of SCLC, without obvious side effects. Conclusions These findings suggested that As 2 O 3 had remarkable inhibitory effects on the endothelial cell activation and SCLC metastasis, and the mechanism might be related to the blocking of calcineurin-NFAT signaling by upregulating DSCR1.

Gorham-Stout syndrome (GSS) is a rare disease characterized by spontaneous and progressive osteolysis caused by benign proliferation of lymphatic vessels or capillaries. It most commonly occurs in children or young individuals without any inherited predisposition. GSS most commonly affects the shoulder girdle, pelvis, ribs and skull. Its diagnosis is mainly based on radiological and pathological findings. The present study reports on the case of a 22-year-old male patient diagnosed with GSS involving the C1-T1 vertebrae accompanied by bilateral pleural effusion. Resection of the occipital and cervical vertebral lesions and spinal reconstruction using an internal fixator were successfully performed via the posterior approach. After the surgery, the patient received bisphosphonate treatment and vitamin D supplementation. The pleural effusion gradually decreased. At the 18-month follow-up visit, no evidence of new bone obstruction was present and the patient had no neurological sequelae.

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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 (χ 2 )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.