Protocadherin alpha 3 inhibits lung squamous cell carcinoma metastasis and epithelial-mesenchymal transition.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. OBJECTIVE: To investigate the functional role of protocadherin alpha 3 (PCDHA3) in LUSC, as well as investigate the underlying molecular mechanism. METHODS: Data for PCDHA3 expression and clinical information in The Cancer Genome Atlas (TCGA) were extracted and analyzed in the UALCAN platform. Expression levels of PCDHA3 in LUSC cell lines were analyzed via RT-PCR and western blot. Overexpression of PCDHA3 was conducted via plasmid transfection. CCK-8 and cell cycle assays were utilized to investigate effect of PCDHA3 on cell proliferation. Transwell assay was used to detect migration and invasion. The underlying mechanism was demonstrated via western blot analysis. RESULTS: Our data indicate that PCDHA3 was low expressed in three kinds of LUSC cell lines and best in H520 cells. Furthermore, overexpression of PCDHA3 could significantly impair LUSC cells proliferation, invasion and migration. Moreover, PCHDA3 repressed the biomarkers of mesenchymal (N-cadherin, fibronectin and vimentin) and increased expression of epithelial markers (E-cadherin and α-catenin). On the other hand, PCDHA3 overexpression partially blocked epithelial-mesenchymal transition. CONCLUSIONS: PCDHA3 suppressed the LUSC cells proliferation, invasion and migration via inhibiting the expression of EMT signatures, suggesting that PCDHA3 could serve as a valuable therapeutic target for LUSC therapy.

Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study

BackgroundCOVID-19 is an emerging disease caused by the SARS-CoV-2 virus; no specific medication has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19. MethodsThis single-center, retrospective, and observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth Peoples Hospital between January 20 and March 15, 2020. Demographic information, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and eight patients with mild and severe symptoms, respectively. FindingsAll 55 patients recovered. Fifty-three patients (96{middle dot}36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all eight severe-group patients (median treatment: 17{middle dot}5 days; four received lopinavir/ritonavir). Twenty-nine patients (52{middle dot}72%) were administered antibiotics, including 21 in the mild group (median treatment: 13{middle dot}5 days; 15 received moxifloxacin) and all eight in the severe group (median treatment: 9 days; two received linezolid). Moreover, seven patients (12{middle dot}72%) were treated with glucocorticoids and nine (16{middle dot}36%) with immunomodulators. InterpretationGiven the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary. FundingThis work was supported by the Shenyang Major Science and Technology Innovation R&D Program (JY2020-9-018 to Y. Chen).

Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity

ImportanceRisk factors associated with COVID-19, the viral pneumonia originating in Wuhan, China, in Dec 2019, require clarification so that medical resources can be prioritized for those at highest risk of severe COVID-19 complications. Infection with M. tuberculosis (MTB), the pathogen that causes TB and latently infects [~]25% of the global population, may be a risk factor for SARS-CoV-2 infection and severe COVID-19 pneumonia. ObjectiveTo determine if latent or active TB increase susceptibility to SARS-COV-19 infection and disease severity, and lead to more rapid development of COVID-19 pneumonia. DesignAn observational case-control study of 36 confirmed COVID-19 cases from Shenyang, China, conducted in Feb 2020. Final date of follow-up: Feb 29, 2020. Cases were grouped according to COVID-19 pneumonia severity (mild/moderate, severe/critical), and MTB infection status compared. Comparisons were made with MTB infection data from another case-control study on bacterial/viral pneumonia at Shenyang Chest Hospital. SettingMulti-center study involving three primary care hospitals in Shenyang, China. Participants86 suspected COVID-19 cases from participating primary-care hospitals in Shenyang. All 36 SARS-CoV-2 +ve cases (based on RT-PCR assay) were included. Disease severity was assessed using the Diagnostic and Treatment Guidelines of the National Health Commission of China (v6). Mean age, 47 years (range: 25-79), gender ratio, 1:1. ExposuresConfirmed COVID-19 pneumonia. Interferon-gamma Release Assays (IGRA) were performed using peripheral blood to determine MTB infection. Main Outcome and MeasuresEpidemiological, demographic, clinical, radiological, and laboratory data were collected. Comparison of MTB infection status between patients with mild/moderate and severe/critical COVID-19 pneumonia. ResultsMean age of 36 COVID-19 patients: 47 (range: 25-79); M/F: 18/18; Wuhan/Hubei connection: 42%. Mild/moderate cases: 27 (75%); severe/critical: 9 (25%). MTB infection (IGRA+ve): 13 cases (36.11%), including 7 of 9 severe/critical cases. MTB infection rate: higher in COVID-19 (36.11%) than bacterial pneumonia (20%; p=0.0047) and viral pneumonia patients (16.13%; p=0.024). MTB infection more common than other co-morbidities (36.11% vs diabetes: 25%; hypertension: 22.2%; coronary heart disease: 8.33%; COPD: 5.56%). MTB co-infection linked with disease severity (severe/critical 78% vs mild/moderate cases 22%; p=0.0049), and rate of disease progression: infection to development of symptoms (MTB+SARS-CoV-2: 6.5{+/-}4.2 days vs SARS-COV-2: 8.9{+/-}5.2 days; p=0.073); from symptom development to diagnosed as severe (MTB+SARS-CoV-2: 3.4{+/-}2.0 days vs SARS-COV-2: 7.5{+/-}0.5 days; p=0.075). Conclusions and RelevanceMTB infection likely increases susceptibility to SARS-CoV-2, and increases COVID-19 severity, but this requires validation in a larger study. MTB infection status of COVID-19 patients should be checked routinely at hospital admission. Key PointsO_ST_ABSQuestionC_ST_ABSIs latent or active tuberculosis (TB) a risk factor for SARS-CoV-19 infection and progression to severe COVID-19 pneumonia? FindingsIn this observational case-control study of 36 COVID-19 cases from Shenyang, China, we found tuberculosis history (both of active TB and latent TB) to be an important risk factor for SARS-CoV-2 infection. Patients with active or latent TB were more susceptible to SARS-CoV-2, and COVID-19 symptom development and progression were more rapid and severe. MeaningTuberculosis status should be assessed carefully at patient admission and management and therapeutic strategies adjusted accordingly to prevent rapid development of severe COVID-19 complications.

Antitumor effect of recombinant human endostatin combined with cisplatin on rats with transplanted Lewis lung cancer

Objective:To observe the antitumor effect and mechanism of recombinant human endostatin (Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats.Methods:A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor (VEGF) concentration in rats’plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density (MVD) in each group. Results:The volume and mass of tumor in Groups B and C were significantly lower than Group A (P< 0.05) while the tumor volume and mass in Group C were significantly lower than Group B (P < 0.05). The antitumor rate in Group C was significantly higher than Group B (P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B (P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A (P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor.Conclusions:Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.

Expression of OPN protein in lung squamous cell carcinoma tissue and its clinical signiifcance / 中国癌症杂志

Background and purpose:Osteopontin (OPN) is a secreted glyco-phosphoprotein, which is overex-pressed by numerous human cancers, invovled in tumor occurrence, development and prognosis. OPN up-regulates matrix metal proteases (MMPs) expression in a NF-κB-dependent fashion during extracellular matrix (ECM) invasion causing degradation of cell basement membrane and ECM leading to tumor invasion and metastasis. The aim of this study was to examine the protein level of OPN in a large number of tissue samples from patients with lung squamous cell carcinoma (SCC), and evaluate its potential clinical value.Methods:The OPN protein levels in 265 tumor tissue samples and corresponding 24 normal lung tissue samples were examined by immunohistochemical (IHC) analysis.Results:IHC results showed that the positive rate of OPN was 64.5% in the SCC tissues, which was significantly higher than that in normal alveoli tissues (29.2%,P<0.001). The positive rate of OPN expression in late stage (Ⅲ+Ⅳ) tissues was 78.4%, significantly higher than that in early stage (Ⅰ+Ⅱ) tissue(positive rate 54.5%,P<0.001). The positive rate of OPN expression in T3-4 stage (Ⅲ+Ⅳ) tissue was 76.9%, significantly higher than that in T1-2 stage tissue (positive rate 59.4%,P=0.007). The expression of OPN was signifcantly correlated with the status of lymph node metastasis (LNM). The positive rate in the tumor tissue with LNM was 73.4%, significantly higher than that without (positive rate 51.4%,P<0.001).Conclusion:The level of OPN protein was overexpressed in lung cancer tissues, involved in SCC carcinogenesis and LNM. It is indicated that OPN has an impor-tant reference value in diagnosis, prognosis and therapy of SCC.

Relationship between Platelets and Serum Thrombopoietin in Rheumatoid Arthritis / 天津医药

Objective: To investigate the relationship between platelets and serum thrombopoietin (TPO) in rheumatoid arthritis (RA) and the mechanism of RA with thrombocytosis thereof. Methods: The clinical data of 57 patients with RA were analyzed. Patients were divided into two groups by platelet count: high platelet count(>300×109/L) and normal platelet count. There were 28 healthy persons as control. Serum levels of TPO and interleukin (IL)-6 were measured using enzyme-linked immunosorbent assay(ELISA) in patients with RA and healthy controls. Results:(1)Serum TPO and IL-6 were higher in RA with thrombocytosis than those of healthy controls(P ＜ 0.05). Compared the two RA groups, the one with thrombocytosis had higher serum TPO(P ＜ 0.05). (2)The platelet count of RA with thrombocytosis did not correlate with serum level of TPO. It correlated significantly with serum level of IL-6 (r ＝ 0.566, P ＜ 0.01) and C-reactive protein (CRP) (r ＝ 0.401, P ＜ 0.05). (3)The serum level of TPO in RA with thrombocytosis did not correlate with serum IL-6 (r ＝ -0.069, P ＞ 0.05). Conclusion: The serum level of TPO was significantly elevated in RA with thrombocytosis, which suggested that TPO may take part in the pathology of thrombocytosis in RA. The thrombocytosis in RA correlated with inflammatory reaction.

Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients / 中国肺癌杂志

<p><b>BACKGROUND</b>Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.</p><p><b>METHODS</b>Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .</p><p><b>RESULTS</b>Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .</p><p><b>CONCLUSIONS</b>The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .</p>