Publications by authors named "Shengcai Hou"

15 Publications

  • Page 1 of 1

Experimental study of the inhibition effect of CXCL12/CXCR4 in malignant pleural mesothelioma.

J Investig Med 2019 02 26;67(2):338-345. Epub 2018 Oct 26.

Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, California, USA.

Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.
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http://dx.doi.org/10.1136/jim-2018-000839DOI Listing
February 2019

Lung volume reduction surgery in hypercapnic patients: a single-center experience from China.

J Thorac Dis 2018 Aug;10(Suppl 23):S2698-S2703

Department of Thoracic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Background: Lung volume reduction surgery (LVRS) has shown early promise as a palliative therapy in severe emphysema, but with a controversy over its indications. The aim of this study was to evaluate whether patients with hypercapnia should be excluded from LVRS.

Methods: Total 15 cases of severe emphysema with the level of PaCO exceeding 50 mmHg were retrospectively studied. Their basic characteristics, pulmonary function, preoperative and postoperative PaCO level as well as postoperative complications were calculated statistically.

Results: All of the 15 patients received video-assisted thoracoscopic LVRS and finally discharged uneventfully from hospital after the surgical procedures. Nine cases were supported by mechanical ventilation after surgery with the median duration of 44 hours. One of them was treated by extracorporeal membrane oxygenation (ECMO) both during surgery and the first 4 days after surgery. The result of blood gas analysis on 3 months after hospital discharge decreased than that before surgery (60.07 55.61 mmHg, P=0.076), but without statistical significance.

Conclusions: The emphysematous patients with hypercapnia should not be excluded from the benefits of LVRS.
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http://dx.doi.org/10.21037/jtd.2018.05.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129801PMC
August 2018

The significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for predicting venous thromboembolism: a prospective, single center study.

J Thorac Dis 2018 Apr;10(4):2223-2230

Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

Background: The high incidence of venous thromboembolism (VTE) has been perceived in post thoracic surgery patients. However, the significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for VTE predicting is not clear. To investigate that, we conducted a prospective single center study.

Methods: A total of 111 patients undergoing lung surgery were enrolled in this study, included 52 primary lung cancer patients and 59 benign lung disease patients from July 2016 to March 2017. Preoperative and postoperative days 1, 3, and 5 coagulation and fibrinolysis related parameters were tested, including antithrombin (AT), fibrinogen degradation product (FDP), prothrombin time (PT), prothrombin time activity (PA), prothrombin time ratio (PR), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (FBG), thrombin time (TT) and D-Dimer. The Doppler ultrasonography was performed before and after surgery for deep venous thrombosis (DVT) confirmation. Patients with new postoperative DVT, unexplained dyspnea, hemoptysis, chest pain, or high Caprini score (≥9) were received further computer tomography pulmonary angiography (CTPA) for pulmonary embolism (PE). We used the area under receiver-operating-characteristic (ROC) curve to discriminate patients between those who developed VTE and those who did not. Single factor analysis was utilized to define risk factors associated with VTE.

Results: The overall incidence of VTE was 16.2% (18/111). The incidence of VTE in primary lung cancer patients was 23.1% (12/52), much higher than that in benign lung diseases 10.2% (6/59), but did not reach statistical significance (P=0.066). Among 18 VTE patients, 83.3% was DVT, 16.7% was DVT + PE and 72.2% was muscular veins of the calf thrombosis. D-Dimer was much higher in VTE group than that in non-VTE group preoperatively and at postoperative days 1, 3 (0.64±0.24 0.33±0.06, P=0.007; 3.14±0.75 1.51±0.09, P=0.005, and 1.88±0.53 0.76±0.05, P=0.001, respectively). And the ROC curve areas of preoperative and postoperative days 1, 3 of D-Dimer were 0.70, 0.71 and 0.74, respectively. And FDP was much higher in VTE group than that in non-VTE group at postoperative day 3 (6.78±1.43 3.79±0.15, P=0.004). But AT, PT, PA, PR, INR, APTT, FBG and TT there were no significantly difference.

Conclusions: The overall incidence of VTE after lung surgery was 16.2%. The patients with preoperative high D-Dimer should receive VTE prophylaxis.
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http://dx.doi.org/10.21037/jtd.2018.03.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949486PMC
April 2018

Transfer of multiple loci of donor's genes to induce recipient tolerance in organ transplantation.

Exp Ther Med 2018 Jun 13;15(6):4961-4971. Epub 2018 Apr 13.

Thoracic Oncology Laboratory, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143-1724, USA.

Donor organ rejection remains a significant problem. The present study aimed to assess whether transferring a donor's major histocompatibility complex (MHC) genes to the recipient could mitigate rejection in organ transplantation. Seven loci of MHC genes from donor mice were amplified and ligated into vectors; the vectors either contained one K locus, seven loci or were empty (control). The vectors were subsequently injected into the thymus of recipients (in heterotransplants, recipient rats received the vector containing one K locus), following which donor mouse hearts were transplanted. Following the transplantation of allograft and heterograft, electrocardiosignals were viable for a significantly longer duration in recipient mice and rats receiving the donor histocompatibility-2 complex (H-2) genes compared with those in controls, and in mice that received seven vectors compared with those receiving one vector. Mixed lymphocyte cultures containing cells from these recipients proliferated significantly less compared with mixed lymphocyte cultures containing controls. Also, hearts from H-2 genes-treated recipients demonstrated less lymphocyte infiltration and necrosis compared with the control recipient. The present study concluded that allograft and heterograft rejection may be mitigated by introducing the donor's MHC into the recipient; transferring seven loci has been demonstrated to be more effective than transferring one locus.
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http://dx.doi.org/10.3892/etm.2018.6058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958787PMC
June 2018

Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax.

J Thorac Dis 2016 Jun;8(6):1188-96

1 Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China ; 2 Beijing Institute of Respiratory Medicine, Beijing 100020, China ; 3 Department of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China ; 4 Center of Health Examination, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

Background: To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP.

Methods: Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD).

Results: Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP.

Conclusions: It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in PSP patients. 25-OH VD expression was relatively low in this population of PSP patients. Age, height, weight, and expression levels of TRACP5b and 25-OH VD may be risk factors for PSP.
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http://dx.doi.org/10.21037/jtd.2016.04.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886012PMC
June 2016

The dynamic of nasogastric decompression after esophagectomy and its predictive value of postoperative complications.

J Thorac Dis 2016 Feb;8(Suppl 1):S99-S106

Department of Thoracic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Background: To investigate the regularity and the influence factors of nasogastric decompression volume after esophagectomy, and explore whether the volume of nasogastric decompression can be employed as a predictor for postoperative complications of esophageal carcinoma.

Methods: Consecutive 247 patients with esophageal cancer who underwent esophagectomy were retrospectively evaluated. The volume of postoperative nasogastric decompression was recorded and the regularity based on it was described. The single and multiple factors regression analysis were used to find out relative factors of the nasogastric decompression volume among the patients without postoperative complication. Gender, age, height, weight, tobacco or alcohol exposure, location of the tumor, histological type, pathological staging, operation time, surgical procedures, anastomotic position and gastric conduit reconstruction were considered as the independent variable. Then, verify the former regression models using the data of patients with postoperative complications.

Results: In trend analysis, the curve estimation revealed a quadratic trend in the relationship between nasogastric decompression volume and postoperative days (R(2) =0.890, P=0.004). The volume of postoperative nasogastric decompression was described by daily drainage (mL) =82.215 + 69.620 × days - 6.604 × days(2). The results of multiple linear stepwise regression analysis showed that gastric conduit reconstruction (β=0.410, P=0.000), smoking (β=-0.231, P=0.000), age (β=-0.193, P=0.001) and histological type of the tumor (β=-0.169, P=0.006) were significantly related to the volume of nasogastric decompression. The average drainage in 5 days after surgery =262.287 + 132.873 × X1 - 72.160 × X2 - 27.904 × X3 - 36.368 × X4 (X1, gastric conduit reconstruction; X2, smoking; X3, histological type; X4, age). The nasogastric decompression of the patients with delayed gastric emptying, and lung infection statistically differ from their predictive values respectively according to the former equation (P<0.01), but the data of anastomotic leakage cases had no significance difference (P=0.344).

Conclusions: It is found that the volume of postoperative nasogastric decompression presents a quadratic trend based on the days after esophagectomy. Gastric conduit reconstruction, smoking history, age and histological type were independent factors affecting on the volume of postoperative nasogastric decompression. Also, the volume of nasogastric decompression has validity and application value for predicting postoperative complications.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2015.10.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756234PMC
February 2016

[A comparative study of HRCT and pathological subtype, EGFR gene mutations of peripheral small lung adenocarcinoma].

Zhonghua Yi Xue Za Zhi 2015 Sep;95(33):2673-6

Department of Thoracic, Chaoyang Hospital, Capital Medwal University, Beijing 100020, China; Email:

Objective: To investigate the relationship of the preoperative HRCT, postoperative pathological subtype and EGFR gene mutation types in the patients of small peripheral lung adenocacinoma confirmed by operation.

Methods: Between December 2011 and November 2014, Ninety-four invasive adenocarcinoma patient were selected from 156 patients with pulmonary nodule underwent operation in Beijing Chaoyang hospital. Among them, there were male 37 cases, female 57 cases, age range from 32 to 76, mean age 52.6. All patients underwent complete anatomical lobectomy or wedge resection or segmentectomy, with systematic mediastinal lymph node dissection. The detection indexes included: preoperative HRCT, postoperative pathological subtypes, lymph node; EGFR, Kras, ALK, FGF9 gene expression and so on.

Results: Postoperative pathologic acinar predominant accounted for 33.0% (31/94), papillary predominant type accounted for 25.5% (24/94), Lepidic predominant adenocarcinoma accounted for 19.1% (18/94), 13.8%(13/94) micro papillary predominant, 8.5% (8/94) solid predominant. 7 patients with lymph node positive included 5 cases of stations 11-12, 1 case of station 4 and 1 case of station 7. 36 cases was detected EGFR mutation after operation (38.9%, 36/94), mainly 19⁺ and 21⁺. Compared with the preoperative HRCT findings, there was no significant difference in EGFR mutation group and non mutation group (χ² = 1.411, P=0.703). For different types of mutations in EGFR gene, there was no statistical difference (P>0.05). But the rate of EGFR 21 positive in progression patients was significantly higher than that of EGFR 19 positive patients(χ² = 5.779, P=0.016).

Conclusion: There were no significant different between the HRCT manifestations and pathological subtypes in the rate of EGFR gene mutation. EGFR 21 gene mutation was found in double lung metastasis commonly.
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September 2015

Successful extracorporeal membrane oxygenation therapy as a bridge to sequential bilateral lung transplantation for a patient after severe paraquat poisoning.

Clin Toxicol (Phila) 2015 Nov 28;53(9):908-13. Epub 2015 Aug 28.

a Department of Respiratory and Critical Care Medicine , Beijing Chao-Yang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine , Beijing , China.

Context: Paraquat is a widely used herbicide that can cause severe to fatal poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis associated with respiratory failure is the main cause of death in the later stages of poisoning. There are infrequent reports of successful lung transplants for cases of severe paraquat poisoning. We expect that this successful case will provide a reference for other patients in similar circumstances.

Case Details: A 24-year-old female was sent to the hospital approximately 2 hours after ingesting 50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and severe respiratory failure. On the 34th day after ingestion, she underwent intubation and invasive mechanical ventilation. The patient was evaluated for lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO) was established as a bridge to lung transplantation on the 44th day. On the 56th day, she successfully underwent a bilateral sequential lung transplantation. Through respiratory and physical rehabilitation and nutrition support, the patient was weaned from mechanical ventilation and extubated on the 66th day. On the 80th day, she was discharged. During the 1-year follow-up, the patient was found to be in good condition, and her pulmonary function improved gradually.

Conclusion: We suggest that lung transplantation may be an effective treatment in the end stages of paraquat-induced pulmonary fibrosis and consequential respiratory failure. For patients experiencing a rapid progression to a critical condition in whom lung transplantation cannot be performed immediately (e.g., while awaiting a viable donor or toxicant clearance), ECMO should be a viable bridge to lung transplantation.
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http://dx.doi.org/10.3109/15563650.2015.1082183DOI Listing
November 2015

Silencing of tripartite motif (TRIM) 29 inhibits proliferation and invasion and increases chemosensitivity to cisplatin in human lung squamous cancer NCI-H520 cells.

Thorac Cancer 2015 Jan 7;6(1):31-7. Epub 2015 Jan 7.

Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University Beijing, China.

Background: TRIM29 belongs to the tripartite motif (TRIM) protein family. It has been reported to be a tumor suppressor or have oncogenic function in many cancer types. The aim of this study was to investigate whether downregulation of TRIM29 by small interfering ribonucleic acid (siRNA) could inhibit cell proliferation and invasion and increase chemosensitivity to cisplatin in human lung squamous cancer NCI-H520 cells in vitro.

Methods: We transformed TRIM29 siRNA into NCI-H520 cells. Real time reverse transcriptase polymerase chain reaction and Western blotting assay were employed to determine TRIM29 messenger (m)RNA and protein expressions. MTT assay was used to determine the cell proliferation. Transwell invasion assay was used to determine the cell invasion. An Annexin V-propidium iodide (AnnV/PI) staining apoptosis test was used for detecting apoptosis.

Results: TRIM29 siRNA could specifically and efficiently suppress TRIM29 expression at both mRNA and protein levels. Silencing of the TRIM29 by siRNA in NCI-H520 cells inhibited cell proliferation and invasion in vitro. TRIM29 knockdown resulted in chemosensitivity enhancement in NCI-H520 cells.

Conclusion: Downregulation of TRIM29 can lead to potent antitumor activity and chemosensitizing effect in human lung squamous cancer NCI-H520 cells.
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http://dx.doi.org/10.1111/1759-7714.12130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448470PMC
January 2015

Application of extracorporeal membrane oxygenation in giant bullae resection.

Ann Thorac Surg 2015 Mar;99(3):e73-5

Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

A patient with chronic obstructive pulmonary disease and lung bullae was admitted to our hospital. He suffered respiratory failure and was given mechanical ventilation. However, the bullae became more and more large and compressed the lungs on both sides. We managed extracorporeal membrane oxygenation (ECMO) to maintain the patient's blood oxygenation, and performed bullae resection surgery successfully. The patient's pulmonary function recovered gradually after the operation and he returned home. In our experience with this case, ECMO can be used in bullae resection.
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http://dx.doi.org/10.1016/j.athoracsur.2014.11.036DOI Listing
March 2015

The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell.

PLoS One 2013 31;8(5):e65309. Epub 2013 May 31.

Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Capital Medical University, Beijing, China.

Background: The efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer is limited by the acquired drug resistance. Identification the RNAs related to the cisplatin resistance may help to improve clinical response rates.

Methods: Microarray expression profiling of mRNAs, lncRNA and miRNA was undertaken in A549 cells and cisplatin resistant A549/CDDP cells. Differentially expressed mRNAs, lncRNAs and miRNAs, verified by realtime RT-PCR, were subjected to pathway analysis. Expression of NKD2 and β-catenin was assessed by realtime RT-PCR and western blot analysis. The effect of lncRNA AK126698 on cisplatin induced apoptosis was investigated by annexin-V/PI flow cytometry.

Results: In total, 1471 mRNAs, 1380 lncRNAs and 25 miRNAs differentially expressed in A549/CDDP and A549 cells. Among them, 8 mRNAs, 8 lncRNAs and 5 miRNAs differentially expressed in gene chip analysis were validated. High-enrichment pathway analysis identified that some classical pathways participated in proliferation, differentiation, avoidance of apoptosis, and drug metabolism were differently expressed in these cells lines. Gene co-expression network identified many genes like FN1, CTSB, EGFR, and NKD2; lncRNAs including BX648420, ENST00000366408, and AK126698; and miRNAs such as miR-26a and let-7i potentially played a key role in cisplatin resistance. Among which, the canonical Wnt pathway was investigated because it was demonstrated to be targeted by both lncRNAs and miRNAs including lncRNA AK126698. Knockdown lncRNA AK126698 not only greatly decreased NKD2 which can negatively regulate Wnt/β-catenin signaling but also increased the accumulation and nuclear translocation of β-catenin, and significantly depressed apoptosis rate induced by cisplatin in A549 cells.

Conclusion: Cisplatin resistance in non-small-cell lung cancer cells may relate to the changes in noncoding RNAs. Among these, AK126698 appears to confer cisplatin resistance by targeting the Wnt pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065309PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669360PMC
January 2014

Differences in gene expression profiles and carcinogenesis pathways involved in cisplatin resistance of four types of cancer.

Oncol Rep 2013 Aug 3;30(2):596-614. Epub 2013 Jun 3.

Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Capital Medical University, Beijing 100069, PR China.

Cisplatin-based chemotherapy is the standard therapy used for the treatment of several types of cancer. However, its efficacy is largely limited by the acquired drug resistance. To date, little is known about the RNA expression changes in cisplatin-resistant cancers. Identification of the RNAs related to cisplatin resistance may provide specific insight into cancer therapy. In the present study, expression profiling of 7 cancer cell lines was performed using oligonucleotide microarray analysis data obtained from the GEO database. Bioinformatic analyses such as the Gene Ontology (GO) and KEGG pathway were used to identify genes and pathways specifically associated with cisplatin resistance. A signal transduction network was established to identify the core genes in regulating cancer cell cisplatin resistance. A number of genes were differentially expressed in 7 groups of cancer cell lines. They mainly participated in 85 GO terms and 11 pathways in common. All differential gene interactions in the Signal-Net were analyzed. CTNNB1, PLCG2 and SRC were the most significantly altered. With the use of bioinformatics, large amounts of data in microarrays were retrieved and analyzed by means of thorough experimental planning, scientific statistical analysis and collection of complete data on cancer cell cisplatin resistance. In the present study, a novel differential gene expression pattern was constructed and further study will provide new targets for the diagnosis and mechanisms of cancer cisplatin resistance.
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http://dx.doi.org/10.3892/or.2013.2514DOI Listing
August 2013

Mediastinal small-cell lung carcinoma after right lung transplant for pulmonary interstitial fibrosis.

Tumori 2012 Mar-Apr;98(2):39e-42e

Department of Thoracic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Pulmonary carcinoma is uncommon after lung transplant, but doubtlessly affects recipient survival independently of other complications. Small cell lung cancer is much rarer after transplant than non-small cell lung cancer. We report a case of mediastinal small cell lung carcinoma confirmed by endobronchial ultrasound biopsy that occurred 18 months after a single lung transplant for interstitial pulmonary fibrosis in a 58-year-old male nonsmoker. The patient died shortly after of distant metastasis. Our report confirms the usefulness of tumor markers and positron-emission tomography-computed tomography as routine tests for earlier detection of malignant disease after lung transplant.
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http://dx.doi.org/10.1700/1088.11946DOI Listing
August 2012

Activation of volume-sensitive Cl(-) channel is involved in carboplatin-induced apoptosis in human lung adenocarcinoma cells.

Cancer Biol Ther 2010 Jun 1;9(11):885-91. Epub 2010 Jun 1.

Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Beijing, China.

The purpose of the present study is to observe the role of volume-sensitive Cl(-) channels in carboplatin-induced apoptosis in the human lung adenocarcinoma cell line A549 cells. Using patch clamp and apoptosis assays, we found that A549 cells underwent the process of apoptotic volume decrease (AVD) and apoptosis when treated with carboplatin or staurosporine (STS). This AVD and apoptosis process were blocked by chloride channel blockers, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3-phenyl propylamino)-benzoate (NPP B). Both carboplatin and STS treatment activated a Cl(-) current, which shows similar properties to hypotonicity-induced volume-sensitive Cl(-) current in A549 cells. In addition, carboplatin pretreatment augmented the magnitude of the hypoosmotic-induced volume-sensitive Cl(-) current. These results suggest that volume-sensitive Cl(-) channels may be responsible for the carboplatin-induced apoptosis in A549 cells by inducing the AVD process.
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http://dx.doi.org/10.4161/cbt.9.11.11666DOI Listing
June 2010