MUC1-EGFR crosstalk with IL-6 by activating NF-κB and MAPK pathways to regulate the stemness and paclitaxel-resistance of lung adenocarcinoma.

BACKGROUND: The chemotherapy resistance often leads to chemotherapy failure. This study aims to explore the molecular mechanism by which MUC1 regulates paclitaxel resistance in lung adenocarcinoma (LUAD), providing scientific basis for future target selection. METHODS: The bioinformatics method was used to analyse the mRNA and protein expression characteristics of MUC1 in LUAD. RT-qPCR and ELISA were used to detect the mRNA and protein expression, flow cytometry was used to detect CD133+ cells, and cell viability was detected by CCK-8 assay. The mRNA-seq was performed to analyse the changes in expression profile, GO and KEGG analysis were used to explore the potential biological functions. RESULTS: MUC1 is highly expressed in LUAD patients and is associated with a higher tumour infiltration. In paclitaxel resistance LUAD cells (A549/TAX cells), the expression of MUC1, EGFR/p-EGFR and IL-6 were higher than that of A549 cells, the proportion of CD133+ cells was significantly increased, and the expression of cancer stem cell (CSCs) transcription factors (NANOG, OCT4 and SOX2) were significantly up-regulated. After knocking down MUC1 in A549/Tax cells, the activity of A549/Tax cells was significantly decreased. Correspondingly, the expression of EGFR, IL-6, OCT4, NANOG, and SOX2 were significantly down-regulated. The mRNA-seq showed that knocking down MUC1 affected the gene expression, DEGs mainly enriched in NF-κB and MAPK signalling pathway. CONCLUSION: MUC1 was highly expressed in A549/TAX cells, and MUC1-EGFR crosstalk with IL-6 may be due to the activation of NF-κB and MAPK pathways, which promote the enrichment of CSCs and lead to paclitaxel resistance.

The risk of immediate pneumothorax after CT-guided lung needle biopsy: pleural tail sign as a novel factor.

Background: Pneumothorax is the most frequent complication in computed tomography-guided lung needle biopsy (CT-LNB) and generally appears immediately or within an hour after CT-LNB. Preventing pneumothorax after CT-LNB requires a preoperative evaluation of risk factors. This study investigated risk factors for the occurrence of immediate pneumothorax after CT-LNB. Methods: A total of 311 CT-LNB procedures were conducted for 290 patients (217 males and 73 females) with persistent solid or part-solid pulmonary lesions in this case-control study. We retrospectively evaluated immediate postbiopsy pneumothorax complications and associated risk factors. The possible risk factors for immediate pneumothorax were analyzed, including 12 parameters in demographics, radiological features, and procedural factors. Univariate and multivariate logistic regression analyses were used to investigate independent risk factors for the occurrence of immediate pneumothorax after CT-LNB. Results: All CT-LNB procedures (100%) were technically successful. Immediate pneumothorax after CT-LNB occurred in 115 out of the 311 procedures (36.9%). Chest tube placement was required for 12.2% (14/115) of the pneumothoraces (14/311, 4.5% of the total number of CT-LNB procedures). The other pneumothoraces were treated conservatively. Independent risk factors of immediate pneumothorax included a lesion with pleural tail sign [PTS; odds ratio (OR) =3.021, 95% confidence interval (CI): 1.703-5.359; P<0.001], smaller lesion size (OR =0.827, 95% CI: 0.705-0.969; P=0.019), a lesion in the middle or lower lobe (OR =2.237, 95% CI: 1.267-3.951; P=0.006), a higher number of pleural punctures (OR =2.710, 95% CI: 1.399-5.248; P=0.003), and a deep-seated lesion (OR =1.622, 95% CI: 1.261-2.088; P<0.001). Conclusion: PTS is a novel risk factor for immediate pneumothorax and may increase the immediate pneumothorax rate after CT-LNB. Practitioners should be vigilant of the risk of immediate pneumothorax after CT-LNB in lung lesions with PTS.

Multiview Deep Forest for Overall Survival Prediction in Cancer.

Overall survival (OS) in cancer is crucial for cancer treatment. Many machine learning methods have been applied to predict OS, but there are still the challenges of dealing with multiview data and overfitting. To overcome these problems, we propose a multiview deep forest (MVDF) in this paper. MVDF can learn the features of each view and fuse them with integrated learning and multiple kernel learning. Then, a gradient boost forest based on the information bottleneck theory is proposed to reduce redundant information and avoid overfitting. In addition, a pruning strategy for a cascaded forest is used to limit the impact of outlier data. Comprehensive experiments have been carried out on a data set from West China Hospital of Sichuan University and two public data sets. Results have demonstrated that our method outperforms the compared methods in predicting overall survival.

Development and validation of a nomogram for predicting overall survival of gastric cancer patients after D2R0 resection.

OBJECTIVE: The aim of the study was to find factors associated with overall survival (OS) and establish a nomogram predicting OS of patients with gastric cancer (GC) after D2R0 resection. METHODS: Demographic and clinicopathologic factors of patients with GC underwent D2R0 surgical resection were retrospectively collected from medical records, telephone interview or outpatient follow-up. To find factors significantly associated with OS, univariate and multivariate analyses were conducted. The concordance index (C-index) was used to measure the accuracy of the nomogram. Discrimination and calibration of the nomogram were tested using the patients in the validation set. RESULTS: Overall, patients with 890 GC underwent D2R0 surgical resection were included. Based on the results of univariate analysis and multivariate analysis, T stage, number of metastatic local lymph nodes, lymph node positive rate, adjuvant chemotherapy and diameter of tumour were used to construct a nomogram predicting OS of patients with GC after surgical resection. In the validation cohort, the C-index was 0.73 and the nomogram performed well in predicting OS. CONCLUSION: The nomogram was able to accurately predict OS of patients with GC underwent curative surgery and performed well in internal validation, which would also be useful for the decision-making of doctors.

[Effects of shRNA on Cisplatin-resistant Non-small Cell Lung Cancer Cell A549 via Silencing CCAT2].

OBJECTIVE: To investigate the effects of short hairpin RNA (shRNA) on the proliferation, invasion, apoptosis and tumor formation of non-small cell lung cancer cisplatin-resistant cell line (A549/DDP) via silencing of colon cancer associated transcript 2 ( CCAT2). METHODS: TA549/DDP cells were transfected with shRNA- CCAT2 (sh- CCAT2) or shRNA-negative control (shRNA-NC), and untransfected A549/DDP cells were used as the control group. CCAT2 mRNA expression in three groups of A549/DDP cells was detected by quantitative real-time PCR (qRT-PCR). The proliferation of three groups of A549/DDP cells treated with different mass concentrations of DDP (0-8 mg/L) was detected by MTT. According to the proliferation experiment results, 2 mg/L was selected as DDP concentration for subsequent experiments. The effects of 2 mg/L DDP treatment on the proliferation, apoptosis, and invasion ability of each group of cells (with untreated A549/DDP cells as the control group) were tested by clone formation experiments, flow cytometry analysis and Transwell experiments. The expression levels of cell proliferation marker proteins (Ki67, PCNA), apoptosis marker proteins (Caspase-3, Caspase-9) and invasion marker proteins (VEGF, MMP-14) were detected by Western blot. Nude mice were injected subcutaneously with A549/DDP cells, A549/DDP cells transfected with shRNA-NC or A549/DDP cells transfected with sh- CCAT2. DDP was intraperitoneally injected at the concentration of 2 mg per kilogram of mice body weight totally for 7 times with an interval of 3 d. A control group was injected subcutaneously with A549/DDP cells, and an equal volume of normal saline instead of DDP was injected intraperitoneally. The tumor volume was detected every 5 d for a total of 30 d. Mice were sacrificed and tumor tissues were taken out 30 d later. CCAT2 mRNA expression level in tumor tissues was detected by RT-PCR, and tumor cell apoptosis was detected by TUNEL staining. RESULTS: Compared with the control group and the shRNA-NC transfection group, the expression level of CCAT2 mRNA was decreased in sh- CCAT2 transfected A549/DDP cells ( P<0.01). The decrease degree of cell proliferation was more pronounced after treating with 2 to 8 mg/L of DDP ( P<0.01). Compared with the control group, in the three groups that treated with DDP, the formation of clones and the expression of proliferation marker proteins Ki67 and PCNA were reduce ( P<0.01), while the rate of apoptosis and the expression of apoptosis marker proteins Caspase-3 and Caspase-9 were increased ( P<0.01). Also, the number of invasion cell and the expression of invasion marker proteins VEGF and MMP-14 were reduced in the three groups that treated with DDP ( P<0.01). Among the three groups of DDP-treated cells, the changes in sh- CCAT2 transfected cells was the most obvious ( P<0.01). Compared with the control group, the tumor volume of the three DDP treatment groups was smaller and the differences were statistically significant at 30 d ( P<0.01). The expression of CCAT2 mRNA was decreased in tumor tissues ( P<0.01), while apoptosis increased ( P<0.01). Among the three DDP treatment groups, the A549/DDP cell group transfected with sh- CCAT2 showed the most notable changes ( P<0.01). CONCLUSION: sh- CCAT2 can inhibit the proliferation of A549/DDP cells, induce apoptosis and reduce the cell invasion ability, thereby inhibiting the growth of A549/DDP cells.

Apatinib for salvage treatment of advanced malignant pleural mesothelioma: A case report.

RATIONALE: Malignant Pleural Mesothelioma (MPM) is rare cancer and has a poor prognosis with resistance to chemotherapy or radiotherapy. Until now there is no standard third-line treatment for patients who have failed second-line therapy. PATIENT CONCERNS: A 58-year-old non-smoking female peasant of ethnic Han was admitted to the oncology department of the 363 Hospital with a primary complaint of chest tightness and breathlessness from 3 months ago. DIAGNOSES: Positron emission tomography-computed tomography (PET/CT) examination showed "dirty" pleural and parietal pleural involvement as well as mediastinal and pulmonary hilar lymph node enlargement. Finally, cancer cells were seen after repeated pleural effusion cell examination. Immunohistochemistry confirmed epithelioid of pleural mesothelioma. INTERVENTIONS: Apatinib as a third-line treatment after failure from pemetrexed/cisplatin (PC) as the first-line chemotherapy and gemcitabine/cisplatin (GP) as the second-line chemotherapy. At first, 250 mg/day was given and 1 week later, the dose was increased to 500 mg/day. OUTCOMES: A 5-month progression-free survival was achieved and toxicity included severe hand-foot syndrome, mild proteinuria, and hypertension. LESSONS: Apatinib may be a potential therapeutic drug for MPM, particularly as a third-line treatment in cases resistant to chemotherapeutic options.

Potential diagnostic value of serum p53 antibody for detecting colorectal cancer: A meta-analysis.

Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS). The result of pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were analyzed and compared with overall accuracy measures using diagnostic odds ratios (DORs) and area under the curve (AUC) analysis. Publication bias and heterogeneity were also assessed. A total of 11 trials that enrolled a combined 3,392 participants were included in the meta-analysis. Approximately 72.73% (8/11) of the included studies were of high quality (QUADAS score >7), and all were retrospective case-control studies. The pooled sensitivity was 0.19 [95% confidence interval (CI), 0.18-0.21] and pooled specificity was 0.93 (95% CI, 0.92-0.94). Results also demonstrated a PLR of 4.56 (95% CI, 3.27-6.34), NLR of 0.78 (95% CI, 0.71-0.85) and DOR of 6.70 (95% CI, 4.59-9.76). The symmetrical summary receiver operating characteristic curve was 0.73. Furthermore, no evidence of publication bias or heterogeneity was observed in the meta-analysis. Meta-analysis data indicated that s-p53 antibody possesses potential diagnostic value for CRC. However, discrimination power was somewhat limited due to the low sensitivity.

Successful Chemo-Radiotherapy for Primary Anaplastic Large Cell Lymphoma of the Lung: A Case Report and Literature Review.

BACKGROUND: Primary anaplastic large cell lymphoma (ALCL) of the lung is an extremely rare disease. This disease is a great challenge for pneumologists due to its nonspecific clinical presentations and radiological findings. Appropriate invasive biopsy and immunohistochemistry are important for diagnosis. There is currently no standard treatment. CASE REPORT: We report a very rare case of primary pulmonary ALCL in a 39-year-old man. The clinical features, imaging, pathological findings, treatment outcomes, and prognosis, are described. Successful treatment outcomes were achieved after 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed by involved field radiotherapy of 54 Gy/27f. The patient was disease-free after follow-up for 65 months. CONCLUSIONS: Our study found that chemotherapy (such as CHOP) is recognized as the first-line regimen for primary ALCL of the lung. For patients with dyspnea caused by a mass blocking the main bronchus, chemo-radiotherapy may be a reasonable therapeutic option. The prognosis is better for patients with positive ALK staining. CD56(+), age older than 60 years, Ann Arbor stage III or IV, survivin expression, PS>2, and high serum LDH level and IPI scores are the poor prognostic factors of ALCL.

Cost-effectiveness of sorafenib as a first-line treatment for advanced hepatocellular carcinoma.

OBJECTIVE: Sorafenib has been shown to significantly improve the overall survival of patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the cost-effectiveness of sorafenib as a first-line treatment for patients with advanced HCC. MATERIALS AND METHODS: To carry out the analysis, we collected the data on the efficacy and safety of patients treated with sorafenib from medical records and follow-up of these patients. A Markov model comprising three health states (progression-free survival, progressive disease, and death) was created to simulate the process of advanced HCC. We calculated the data on cost from the perspective of Chinese patients. Sensitivity analyses were also carried out to explore the impact of several essential variables. RESULTS: Overall, 94 patients with advanced HCC were included in our study: 70 in the Child-Pugh A group and 24 in the Child-Pugh B group. The median overall survival was 8.0 months (95% confidence interval: 7.21-8.50). In general, treatment with sorafenib was estimated to increase costs by $18,251.84 compared with best supportive care, with a gain of 0.18 quality-adjusted life years (QALYs). Thus, the incremental cost-effective ratio was $101,399.11/QALY for sorafenib versus best supportive care. In addition, in patients with Child-Pugh A liver function, the total costs and effectiveness were $20,643.06 and 0.48 QALYs, respectively, whereas in the Child-Pugh class B group, the total costs and effectiveness were $15,844.33 and 0.28 QALYs. CONCLUSION: On the basis of the commonly accepted willingness-to-pay threshold ($20,301.00/QALY in China), sorafenib is not a cost-effective option as a first-line treatment for patients with advanced HCC.

Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

Cost-effectiveness analysis of colon cancer treatments from MOSIAC and No. 16968 trials.

AIM: To compare XELOX and FOLFOX4 as colon cancer adjuvant chemotherapy based on MOSAIC and No. 16968 trails from Chinese cost-effectiveness perspective. METHODS: A decision-analytic Markov model was developed to compare the FOLFOX4 and XELOX regimens based MOSAIC and No. 16968 trial. Five states were included in our Markov model: well (state 1), minor toxicity (state 2), major toxicity (state 3), quitting adjuvant chemotherapy (state 4), and death due to adjuvant chemotherapy (state 5). Transitions among the 5 states were assumed to be Markovian. Costs were calculated from the perspective of the Chinese health-care payer. The utility data were taken from published studies. Sensitivity analyses were used to explore the impact of uncertainty factors in this cost-effectiveness analysis. RESULTS: Total direct costs of FOLFOX4 and XELOX per patient were $19884.96 ± 4280.30 and $18113.25 ± 3122.20, respectively. The total fees related to adverse events per patient during the entire treatment were $204.75 ± 16.80 for the XELOX group, and $873.72 ± 27.60 for the FOLFOX4 group, and the costs for travel and absenteeism per patient were $18495.00 for the XELOX group and $21,352.68 for the FOLFOX4 group. The base-case analysis showed that FOLFOX4 was estimated to produce an additional 0.06 in quality adjusted life years (QALYs) at an additional cost of $3950.47 when compared to the XELOX regimen over the model time horizon. The cost per QALY gained was $8047.30 in the XELOX group, which was $900.98 less than in the FOLFOX4 group ($8948.28). The one way sensitivity analysis demonstrated that the utility for the well state and minor toxicity state greatly influenced the incremental cost-effectiveness ratio of FOLFOX4. CONCLUSION: In term of cost-comparison, XELOX is expected to dominate FOLFOX4 regimes; Therefore, XELOX provides a more cost-effective adjuvant chemotherapy for colon cancer patients in China.

Safety and efficacy of radiation and chemoradiation in patients over 70 years old with inoperable esophageal squamous cell carcinoma.

The aim of the present study was to perform a retrospective analysis to investigate the outcome and toxicity of radiation (RT) and chemoradiation (CRT) in elderly, inoperable patients >70 years old. Between 2003 and 2012, 1,024 patients with squamous cell carcinoma (SCC) of the esophagus were treated at the Department of Thoracic Cancer, West China Hospital (Chengdu, China). Of these patients, 37 were >70 years old and had not undergone surgery, and were selected for analysis. Of these 37 patients, CRT had been administered to 20 (54%). Actuarial survival rates were determined by the Kaplan-Meier method. The one-year survival rate in the CRT group (n=20) was 85%, while 35% of patients in the RT group (n=17) survived for more than one year. The overall and progression-free survival in the CRT group versus the RT group were 17 months [95% confidence interval (CI), 11.861-22.139] versus eight months (95% CI, 6.674-9.326) (P=0.013) and 14 months (95% CI, 9.617-18.383) versus five months (95% CI, 2.311-7.689) (P=0.01), respectively. Patients irradiated with a dose of >50 Gy exhibited an improved survival rate compared with patients who received a dose of ≤50 Gy (18 vs. 14 months; P=0.049). Furthermore, patients with an Eastern Cooperative Oncology Group (ECOG) score of ≤1 had an improved prognosis compared with those with an ECOG score of 2 (14 vs. seven months; P=0.006). The two regimens were well-tolerated and there were no therapy-associated mortalities. The current retrospective study indicated that patients of >70 years old with inoperable esophageal SCC and a good ECOG score exhibit comparably better safety levels with CRT and improved survival rates compared with RT alone.

Which is false: oxaliplatin or fluoropyrimidine? An analysis of patients with KRAS wild-type metastatic colorectal cancer treated with first-line epidermal growth factor receptor monoclonal antibody.

This meta-analysis was performed to determine whether the addition of monoclonal antibodies (mAbs) of epidermal growth factor receptor (EGFR) to oxaliplatin-based chemotherapy treatment improves efficacy in KRAS wild-type metastatic colorectal cancer (mCRC), and whether infusional 5-fluorouracil (5-FU) and oxaliplatin is a preferred combination for EGFR mAbs. Oxaliplatin (including treatment), EGFR mAbs, first-line treatment, KRAS wild-type, and mCRC were used as key words. The PRIME, OPUS, COIN, and NORDIC VII trials were identified by two independent authors. Time-to-event outcomes of overall survival (OS) and progression-free survival (PFS) were analyzed using HRs (hazard ratios) with fixed effect, and response rate (RR) using odd ratios (OR) with fixed effect. A total of 1767 patients who were KRAS wild-type were included in this meta-analysis, with 866 patients in the mAbs and chemotherapy combination group and 901 patients in the chemotherapy alone group. The addition of mAbs to oxaliplatin-based chemotherapy in patients with KRAS wild-type mCRC as first-line treatment resulted in significant improvements in PFS (HR = 0.88; 95% confidence interval (CI), 0.79-0.99; P = 0.03) and response rate (RR) (OR = 1.38; 95% CI, 1.14-1.66; P = 0.009) compared with chemotherapy alone, but the difference in OS was not significant (HR = 0.96; 95% CI, 0.85-1.08; P = 0.48). However, the differences in OS and PFS were not significant when mAbs were added to bolus 5-FU or capecitabine-based regimens compared with chemotherapy alone, whereas PFS improved with an infusional 5-FU and oxaliplatin combination (P = 0.06; PFS, HR = 0.76; 95% CI, 0.65-0.86; P = 0.0002), and even OS was marginally significant, which was consistent with the subgroup analysis of cetuximab and panitumumab. EGFR mAbs combined with oxaliplatin and an infusional 5-FU regimen was associated with significantly improved RR, PFS and OS as first-line treatment in KRAS wild-type mCRC.

Cost analysis of S1 and XELOX as adjuvant therapy for gastric cancer.

Both S1 and XELOX (capecitabine+oxaliplatin) have been recommended as an adjuvant treatment for gastric cancer according to the guidelines of the National Comprehensive Cancer Network (NCCN). This study compared the two regimens in terms of monetary costs, assuming equal efficacy of both regimens. Chemotherapy cost data of 188 patients were collected from the medical records, 91 for the S1 group and 97 for XELOX. Costs were classified as direct costs (chemotherapy, hospitalization, venous access, and tests), adverse event-related treatments costs, and societal (travel and time) costs. The total direct costs of S1 and XELOX per cycle per patient were $1938±236 and $2317±315, respectively. S1 cost $27 and $9 less than XELOX on total adverse event-related costs and societal costs, respectively. The total costs of S1 and XELOX were $1994±322 versus $2410±391 per cycle per patient, respectively. The total cost of S1 was 17.3% less than that of XELOX for the average patient. All the differences were statistically significant. S1, compared with XELOX, could be a more affordable option as an adjuvant treatment for gastric cancer when all healthcare resources are taken into account in China.

First-line irinotecan combined with 5-fluorouracil and leucovorin for high-grade metastatic gastrointestinal neuroendocrine carcinoma.

AIM AND BACKGROUND: High-grade gastrointestinal neuroendocrine neoplasms, ie, poorly differentiated neuroendocrine carcinomas, with no effective therapeutic approaches, have a high ability to metastasize. METHODS: A review of the hospital information system was performed. Patients with histologically proven gastrointestinal neuroendocrine carcinoma who were treated with irinotecan combined with 5-fluorouracil and leucovorin in a first-line setting were eligible for analysis. We extracted information on age, sex, disease stage, laboratory findings, radiological findings, pathological findings, chemotherapy, effectiveness and adverse events of therapy, and outcomes. RESULTS: Eleven patients were included in the study. Partial response was observed in 7 patients. Median progression-free survival and overall survival were 6.5 (95% CI, 5.1-7.9) and 13.0 (95% CI, 9.8-16.2) months, respectively. No treatment-related deaths occurred. CONCLUSIONS: The results demonstrated that irinotecan combined with 5-fluorouracil and leucovorin is an active regimen with acceptable toxicity for patients with metastatic high-grade gastointestinal neuroendocrine carcinoma that merits further investigation in prospective trials.