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Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a form of rare primary liver cancer that combines intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma.To investigate overall survival (OS) and recurrence-free survival (RFS) after radical resection in patients with cHCC-CCA, and the clinicopathological factors affecting prognosis in two center hospitals of China.We reviewed consecutive patients with cHCC-CCA who received radical resection between January 2005 and September 2021 at Peking Union Medical College and the 5th Medical Center of the PLA General Hospital retrospectively. Regular follow-up and clinicopathological characteristics were systematic collected for baseline and prognostic analysis.Our study included 95 patients who received radical resection. The majority of these patients were male and 82.7% of these patients were infected with HBV. The mean tumor size was 4.5 cm, and approximately 40% of patients had more than one lesion. The median OS was 26.8 (95%CI: 18.5-43.0) mo, and the median RFS was 7.27 (95%CI: 5.83-10.3) mo. Independent predictors of OS were CA19-9 ≥ 37 U/mL (HR = 8.68,The overall postoperative survival of cHCC-CCA patients is poor, and most patients experience relapse within a short period of time after surgery. Preoperative tumor biomarker (CA19-9, alpha-fetoprotein) levels, tumor size, and Child-Pugh score can significantly affect OS. Adjuvant TACE after surgery prolongs RFS, suggesting that TACE is a possible option for postoperative adjuvant therapy in patients with cHCC-CCA.

Objective: We analyzed the clinical features and prognosis of advanced intra- and extra-pulmonary neuroendocrine carcinomas (NECs) in order to provide further guidance for the clinical treatment of small-cell lung cancer, which is a type of advanced intrapulmonary NECs. Methods: The clinical data and survival of 123 patients with advanced intra- and extra-pulmonary NECs in the Fujian Medical University Union Hospital, Fujian Province, China, between January 2013 to November 2019 were collected. We retrospectively analyzed the corresponding clinical diagnosis and treatment, and explored the relevant factors affecting the survival prognosis of patients with intra- and extra-pulmonary NECs. Results: The data of 123 patients were collected. There were 90 cases of intra-pulmonary NECS (including 81 cases of small-cell lung cancer, SCLC), 25 cases of extra-pulmonary NECs involving in the gastrointestinal tract, and 8 cases of extra-pulmonary NECs in other regions. The median overall survival (OS) of intra-pulmonary NECs was 13.53 months, of which the median OS of SCLC was 12.97 months, and the median OS of other intra-pulmonary NECs was 27.07 months. The median OS of extra-pulmonary NECs in the gastrointestinal tract was 9.42 months, and the OS of extra-pulmonary NECs in the other regions was 8.69 months. The median OS of intra-pulmonary NECs was significantly longer than that of the extra-pulmonary NECs in the gastrointestinal tract and in the other regions (P < 0.05). Multivariate analysis showed that age, liver metastasis, number of cycles of first-line chemotherapy, and chest radiotherapy were risk factors affecting OS in patients with NECs (P < 0.05). Conclusions: The survival of intra-pulmonary NECs was significantly longer than that of extra-pulmonary NECs of the gastrointestinal tract and in other regions. However, patients with advanced intra- and extra-pulmonary NECs who were older and had liver metastases had a poorer prognosis. Multi-disciplinary treatments such as multi-cycle chemotherapy and combination of chemotherapy and radiotherapy should play an important role in prolonging the survival of NECs.

Background Immune checkpoint inhibitors (ICIs) have been identified as validated medications in non-small cell lung cancer (NSCLC). However, they are often associated with immune-related adverse events (irAEs) including liver dysfunction. Therefore, we conducted a systematic review of the literature and performed a meta-analysis to ascertain overall incidence and risk of immune mediated liver dysfunction in NSCLC patients. Methods PubMed, the Cochrane Library, Embase and ClinicalTrials.gov ( http://clinicaltrials.gov/ ) were searched from inception to December 2019. Studies regarding all grade (1–5), high grade (3–5) hepatitis and ALT or AST elevation were included. Results A total of 11 clinical trials including 7086 patients were selected for further assessment. The overall incidence of ALT elevation, AST elevation and hepatitis for the application of ICIs was 6.18%, 4.99% and 1.09%, respectively. Compared with chemotherapy group, treatment with ICIs had a significantly higher risk of all grade (RR: 7.27, p = 0.001) and high grade (RR: 6.70, p = 0.003) hepatitis. When ICIs combined with chemotherapy, the relative risk of all grade hepatitis was higher than monotherapy group (RR: 7.89, p = 0.044 vs RR: 6.94, p = 0.008). Conclusion The application of ICIs could result in a higher incidence and relative risk of all grade immune-induced liver dysfunction. Moreover, immunotherapy combined with chemotherapy may also increase relative risk of all grade hepatic AEs when compared with monotherapy. Prompt recognition and proper administration is required for clinicians to prevent potentially hepatic deterioration.

BACKGROUND The programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors have shown encouraging merits in non-small cell lung cancer (NSCLC) patients, however, they are often related to potentially fatal immune-related adverse events (irAEs) including colitis. Considering the incidence and characteristics of immune-related colitis may have significant implications for the appropriate utilization of PD-1/PD-L1 inhibitors in clinical practice, we conduct this meta to systematically analyze the correlation between PD-1/PD-L1 inhibitors for the treatment of NSCLC and the incidence of immune-associated colitis. METHODS Electronic databases including PubMed, Embase, Cochrane Library and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched up to May 2019, clinical trials reporting all grade (1-5), higher grade (3-5) colitis and grade 3-5 diarrhea were included, data were expressed as relative risk (RR), incidence, corresponding p value and 95% confidence intervals (CIs). RESULTS 9 randomized controlled trials (RCTs) were identified (7 with PD-1 inhibitors [n = 4526]) and 2 with PD-L1 inhibitors [n = 1464]). The overall incidence of PD-1/PD-L1 target agents was 1.40% for all grade colitis, 0.89% for severe colitis, 11.62% for all grade diarrhea and 1.36% for severe diarrhea. Compared with chemotherapy group, the PD-1/PD-L1 inhibitors had a significantly higher risk of all grade (RR: 3.68, p

The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 µmol/l; S2, 4 µmol/l; S3, 8 µmol/l; and S4, 16 µmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P

Objective To investigate the expression and clinicopathological significance of the oestrogen receptor (ER) in non-small cell lung cancer (NSCLC). Methods ER expression was examined by immunohistochemical staining of tumour tissue and adjacent normal lung tissue from 67 NSCLC patients. The relationships between ER expression and clinicopathological features were analysed. Results A higher percentage of NSCLC tissues (28/67, 41.79%) than adjacent normal lung tissues (10/55, 18.18%) were ER positive. ER expression correlated with tumour differentiation but not with gender, age, tumour histological type, tumour size, lymph node metastasis, or clinical TNM staging. The median survival times of patients with ER-positive ( n = 28) and -negative ( n = 39) tumours were 36 and 27 months, respectively. The 1-, 3-, and 5-year survival rates were higher for patients with ER-positive tumours than for patients with ER-negative tumours. Conclusion ER expression could be a useful prognostic biomarker and therapeutic target for patients with NSCLC.

The survivin protein, a member of the inhibitors of apoptosis (IAP) family, has gained popularity as a therapeutic target for cancer due to its selective expression in tumor cells and its significant involvement in tumor cell viability. The aim of this study was to investigate the effect of the survivin-small interfering RNA (siRNA) plasmid on survivin expression in the human lung cancer cell line, A549, and to observe its effects on apoptosis and proliferation of A549 cells. A549 human lung cancer cells were transfected with survivin-targeting siRNA. The downregulation of survivin expression was determined by real-time polymerase chain reaction and western blotting. The proliferation of A549 cells was determined by MTT assay. The apoptotic rate and cell cycle distribution were analyzed by flow cytometry (FCM). Caspase-9 activity was also detected to study the apoptosis of lung cancer cells induced by siRNA against survivin. The sequence-specific siRNA efficiently and specifically downregulated the expression of survivin at both the mRNA and protein levels. Downregulation of survivin expression dramatically suppressed the proliferation of A549 cells and arrested the cells at the G (1)/G (0) phase. Caspase-9 activity was significantly increased in A549 cells transfected with siRNA against survivin. In this study, we found that survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis and inhibit A549 cell proliferation. Our findings further indicate the possibility that the antitumor effects of survivin-siRNA are mediated through the activation of caspase-9.

Objective: To investigate the effects of interleukin-18 (IL-18) on implanted Lewis lung cancer in suppressing angiogenesis and lymphangiogenesis. Methods: One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group (group A) were intraperitoneally injected with the IL-18 and in the control group (group B) were intraperitoneally injected with normal saline for 7 days. The mice were killed on day 19. The morphology of the tumors was studied, the growth curve was described and the tumor inhibition rate was calculated. The numbers of metastasized pulmonary colonies were calculated using hematoxylin-eosin (HE) staining. The vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor C (VEGF-C), microvessel density (MVD) and lymphatic microvessel density (LMVD) in tumor mass were measured by immunohistochemistry staining (IHCS). Results: In the group A, the tumor volume, tumor weigh, lung metastatic nodules, expression of VEGF-A and VEGF-C, MVD were all decreased significantly (P 0.05). Conclusion: IL-18 could suppress the tumor growth and metastasis of implanted Lewis lung cancer by way of down-regulating VEGF-A and VEGF-C expression, suppressing angiogenesis and lymphangiogenesis.

Objective The aim of our study was to investigate the effects of interleukin-18 (IL-18) on implanted Lewis lung cancer in suppressing tumor growth and inducing tumor cells apoptosis.

To investigate the effects of Interleukin-18 (IL-18) on asthmatic airway inflammation.Thirty healthy adult male guinea pigs were randomly divided into 3 equal groups: asthmatic model group (Group A, undergoing intraperitoneally injection of ovalbumin (OVA) once and spraying of OVA aerosol once a day for 5 days; control group (Group B), undergoing intraperitoneally injection of OVA once and spraying of normal saline aerosol once a day for 5 days; and interleukin (IL)-18 intervention group (Group C, undergoing intraperitoneally injection of OVA once and intraperitoneal injection of IL-18 on the days 1, 3, 8. 10. 15, 17, and 19. Twenty-four hours after the final spraying or IL-18 injection the bronchalveolar lavage fluid (BALF) of the left lungs were obtained. HE staining was conducted to the sediment to examine the numbers of eosinophils, neutrophils, and monocytes. ELISA was used to detect the Th1/Th2 cytokines in the BALF. The left lungs underwent pathological examination.The number of EOS in BALF of Groups A was (98 +/- 58) x 10(6)/L, significantly higher than those of Group B, (12 +/- 10) x 10(6)/L, and Group C, (29 +/- 10) x 10(6)/L (P0.01 and P0.05). The numbers of neutrophils in the BALF of Group A was (24 +/- 16) x 10(6)/L, significantly higher than those of Group B and C [(9 +/- 7) x 10(6)/L and (10 +/- 5) x 10(6)/L respectively, both P0.05]. The concentration of IFN-gamma and IL-2 in group A were both significantly lower than those of Group B and Group C (P0.05 and P0.01). The concentration of IL-4 in Group A was significantly higher than those of Groups B and C (both P0.05). The concentration of IL-5 of Group A was significantly higher than those of Group Bs and C (both P0.01).IL-18 effectively inhibits asthmatic airway inflammation by regulating the Th1/Th2 balance.