Publications by authors named "Lucheng Zhu"

28 Publications

  • Page 1 of 1

Decitabine Sensitizes the Radioresistant Lung Adenocarcinoma to Pemetrexed Through Upregulation of Folate Receptor Alpha.

Front Oncol 2021 17;11:668798. Epub 2021 May 17.

Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, China.

Chemotherapy is the backbone of subsequent treatment for patients with lung adenocarcinoma (LUAD) exhibiting radiation resistance, and pemetrexed plays a critical role in this chemotherapy. However, few studies have assessed changes in the sensitivity of LUAD cells to pemetrexed under radioresistant circumstances. Therefore, the objectives of this study were to delineate changes in the sensitivity of radioresistant LUAD cells to pemetrexed and to elucidate the related mechanisms and then develop an optimal strategy to improve the cytotoxicity of pemetrexed in radioresistant LUAD cells. Our study showed a much lower efficacy of pemetrexed in radioresistant cells than in parental cells, and the mechanism of action was the significant downregulation of folate receptor alpha (FRα) by long-term fractionated radiotherapy, which resulted in less cellular pemetrexed accumulation. Interestingly, decitabine effectively reversed the decrease in FRα expression in radioresistant cells through an indirect regulatory approach. Thereafter, we designed a combination therapy of pemetrexed and decitabine and showed that the activation of FRα by decitabine sensitizes radioresistant LUAD cells to pemetrexed both and in xenografts. Our findings raised a question regarding the administration of pemetrexed to patients with LUAD exhibiting acquired radioresistance and accordingly suggested that a combination of pemetrexed and decitabine would be a promising treatment strategy.
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http://dx.doi.org/10.3389/fonc.2021.668798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165306PMC
May 2021

Cancer-associated fibroblasts in non-small cell lung cancer: Recent advances and future perspectives.

Cancer Lett 2021 Aug 18;514:38-47. Epub 2021 May 18.

Hangzhou Cancer Institution, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Zhejiang University Cancer Center, Hangzhou, 310058, China. Electronic address:

Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer, which is the leading cause of cancer-related deaths in the world. Nearly 70% of NSCLC patients were diagnosed at advanced stage with only 15% of five-year survival rate. Cancer-associated fibroblasts (CAFs) are the major component of tumor microenvironment and account for almost 70% of the cells in tumor tissues. By the crosstalk with cancer cells, CAFs reprogrammed cancer cell metabolism, remodeled extracellular matrix (ECM) and created a supportive niche for cancer stem cells. CAFs lead collective invasion of tumor cells and shape tumor immune microenvironment, promoting tumor metastasis and immune escape. In this review, we have summarized the progress of studies regarding CAFs influences on NSCLC in recent five years from the aspects of cell growth, metabolism, therapy resistance, invasion and metastasis and immune suppression. We have discussed the involved mechanisms and implications for the development of anti-NSCLC therapies. The current strategies of CAFs targeting and elimination have also been generalized. Only better understanding of the molecular biology of CAFs may contribute to the development of novel anti-NSCLC strategies.
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http://dx.doi.org/10.1016/j.canlet.2021.05.009DOI Listing
August 2021

Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study.

BMC Cancer 2021 May 7;21(1):511. Epub 2021 May 7.

Department of Thoracic Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, People's Republic of China.

Background: Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients.

Methods: Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival.

Discussion: The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030.

Trial Registration: clinicaltrials.gov, NCT04636593 . Registered 19 November 2020 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-021-08266-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103745PMC
May 2021

Deep learning-based automatic delineation of the hippocampus by MRI: geometric and dosimetric evaluation.

Radiat Oncol 2021 Jan 14;16(1):12. Epub 2021 Jan 14.

Department of Radiation Oncology, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, China.

Background: Whole brain radiotherapy (WBRT) can impair patients' cognitive function. Hippocampal avoidance during WBRT can potentially prevent this side effect. However, manually delineating the target area is time-consuming and difficult. Here, we proposed a credible approach of automatic hippocampal delineation based on convolutional neural networks.

Methods: Referring to the hippocampus contouring atlas proposed by RTOG 0933, we manually delineated (MD) the hippocampus on the MRI data sets (3-dimensional T1-weighted with slice thickness of 1 mm, n = 175), which were used to construct a three-dimensional convolutional neural network aiming for the hippocampus automatic delineation (AD). The performance of this AD tool was tested on three cohorts: (a) 3D T1 MRI with 1-mm slice thickness (n = 30); (b) non-3D T1-weighted MRI with 3-mm slice thickness (n = 19); (c) non-3D T1-weighted MRI with 1-mm slice thickness (n = 11). All MRIs confirmed with normal hippocampus has not been violated by any disease. Virtual radiation plans were created for AD and MD hippocampi in cohort c to evaluate the clinical feasibility of the artificial intelligence approach. Statistical analyses were performed using SPSS version 23. P < 0.05 was considered significant.

Results: The Dice similarity coefficient (DSC) and Average Hausdorff Distance (AVD) between the AD and MD hippocampi are 0.86 ± 0.028 and 0.18 ± 0.050 cm in cohort a, 0.76 ± 0.035 and 0.31 ± 0.064 cm in cohort b, 0.80 ± 0.015 and 0.24 ± 0.021 cm in cohort c, respectively. The DSC and AVD in cohort a were better than those in cohorts b and c (P < 0.01). There is no significant difference between the radiotherapy plans generated using the AD and MD hippocampi.

Conclusion: The AD of the hippocampus based on a deep learning algorithm showed satisfying results, which could have a positive impact on improving delineation accuracy and reducing work load.
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http://dx.doi.org/10.1186/s13014-020-01724-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807715PMC
January 2021

Prophylactic chemotherapeutic hyperthermic intraperitoneal perfusion reduces peritoneal metastasis in gastric cancer: a retrospective clinical study.

BMC Cancer 2020 Aug 31;20(1):827. Epub 2020 Aug 31.

Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, P.R. China.

Background: Peritoneal metastasis is the most frequent failure in gastric cancer. This study evaluated the role of prophylactic chemotherapeutic hyperthermic intraperitoneal perfusion (CHIP) in patients after D2 dissection.

Methods: Gastric cancer patients after D2 dissection were enrolled in this study. Patients received either chemotherapy (IV group) or CHIP (CHIP group). Sites of recurrence or metastasis, disease-free survival (DFS), overall survival (OS) and adverse events were evaluated.

Results: Twenty-two patients received CHIP treatment, and 21 patients received chemotherapy alone. The median DFS time was 24.5 and 36.5 months in the IV group and CHIP group (P = 0.044), respectively. The median OS time was 33.1 months in the IV group and not reached in the CHIP group (P = 0.037). We also found that CHIP could reduce the total recurrence/metastasis rate, especially that of peritoneal metastasis. In the subgroup analysis, DFS and OS were both superior in deficient mismatch repair (dMMR) patients than in proficient MMR (pMMR) patients.

Conclusion: This hypothesis-generating study indicates that CHIP might be feasible for gastric cancer patients after D2 resection.
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http://dx.doi.org/10.1186/s12885-020-07339-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461269PMC
August 2020

Identification of somatic copy number variations in plasma cell free DNA correlating with intrinsic resistances to EGFR targeted therapy in T790M negative non-small cell lung cancer.

J Thorac Dis 2020 Mar;12(3):883-892

Center for Translational Medicine, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, China.

Background: About 20-30% EGFR-mutant non-small lung cancer show intrinsic resistance to EGFR targeted therapies. Compared to T790M positive in acquired resistance patients, little is known about EGFR-TKI intrinsic resistance for T790M negative patients.

Methods: Thirty-one patients with advanced stage lung cancer, including 18 patients with intrinsic resistance (PFS <6 months) and 13 patients with acquired resistance (PFS >36 months) but are negative for plasma T790M were recruited in the study. Plasma cell free DNA was profiled by low coverage whole genome sequencing with median genome coverage of 1.86X by Illumina X10. Sequencing coverage across chromosomes was summarized by samtools, and normalized by segmentation analysis as provided by R package 'DNACopy'.

Results: The most frequent chromosomal changes were found on chr7, chr1 and chr8. Among them, chr7p gains were found in 12 (66.7%) intrinsic resistance and 4 (30.7%) acquired resistance patients. The gene EGFR was found located on the focal amplification peak of chr7p. The performance of 7p gain to predict intrinsic resistance reaches AUC =0.902. Similarly, focal amplifications were also found on chromosome 5, 16 and 22, where tumor related gene PCDHA, ADAMTS18 and CRKL were located. Focal deletions were also found in chr1, 8, 10 and 16, where genes SFTPA1/2, DLC1, PTEN and CDH1 are located.

Conclusions: The results suggest cell free DNA copy number might be a useful peripheral blood tumor biomarker for predicting intrinsic resistance of EGFR targeted therapy and prognosis.
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http://dx.doi.org/10.21037/jtd.2019.12.97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138977PMC
March 2020

A phase II study of concurrent nab-paclitaxel/carboplatin combined with thoracic radiotherapy in locally advanced squamous cell lung cancer.

J Thorac Dis 2019 Nov;11(11):4529-4537

Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, China.

Background: The development of chemoradiotherapy is urgently needed for locally advanced squamous cell lung cancer due to its poor prognosis and significant toxicity. Carboplatin combined with nab-paclitaxel is a useful choice as first-line therapy in advanced squamous cell lung cancer. This prospective phase II study aimed to explore the efficacy and toxicity of concurrent chemoradiotherapy with nab-paclitaxel, carboplatin, and thoracic radiotherapy in unresectable locally advanced squamous cell lung cancer.

Methods: Patients with unresectable stage III squamous cell lung cancer were eligible. All patients received nab-paclitaxel weekly at a dose of 60 mg/m, in combination with carboplatin [area under the plasma concentration time curve (AUC) 2] weekly during concurrent chemoradiotherapy. Thoracic radiation was administered at a dose of 66 Gy/33 fractions. The consolidation chemotherapy consisted of nab-paclitaxel (260 mg/m on day 1) and carboplatin (AUC 6 on day 1) every 21 days was administered in two cycles after the concurrent chemoradiotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.

Results: Initially, enrollment of 21 patients was planned; however, the trial was prematurely closed due to slow recruitment. Finally, a total of 8 patients were enrolled between January 2012 and July 2015 from one institute. All patients completed concurrent chemoradiotherapy, and 6 patients (75.0%) received consolidation chemoradiotherapy. The ORR was 75%, with complete response (CR) 1 (12.5%), partial remission 6 (62.5%), stable disease 1 (12.5%), progressive disease 1 (12.5%), respectively. After a median follow-up of 15.2 (range, 2.3-51.5) months, 7 patients were dead, and 1 was alive. The median PFS and OS were 12.1 and 15.2 months, respectively. According to Common Terminology Criteria for Adverse Events version 4.0, 6 patients (75.0%) experienced acute radiation esophagitis, 4 (50.0%) were grade 2 (G2), and 2 (25.0%) were G3; 4 patients (50%) experienced acute radiation pneumonitis, 3 (37.5%) were G2, and 1 (12.5%) was G3. No late radiation-induced esophageal and pulmonary toxicity was observed after 1-year follow-up.

Conclusions: Concurrent nab-paclitaxel, carboplatin, and thoracic radiotherapy was shown to be an effective regimen for patients with unresectable locally advanced squamous cell lung cancer; however, further study should exercise caution due to the severe radiation esophagitis.
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http://dx.doi.org/10.21037/jtd.2019.10.81DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940262PMC
November 2019

Regional Hyperthermia Combined with Chemotherapy in Advanced Gastric Cancer.

Open Med (Wars) 2019 20;14:85-90. Epub 2019 Feb 20.

Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, No. 261, Huansha Road, Hangzhou, China.

Introduction: This study aims to investigate the potential effects of regional hyperthermia combined with chemotherapy (RHCT) as a treatment strategy for advanced gastric cancer (AGC).

Method: 118 AGC patients were randomly divided into treatment plans with chemotherapy (CT) alone or with RHCT. The prognostic value of clinicopathologic characteristics was assessed in terms of overall survival of AGC patients.

Results: The disease control rate was determined to be 70.9% and 46.0% for the RHCT and CT group, respectively (P = 0.006). The median survival was determined to be 23.5 months for the RHCT group and 14.0 months for the CT group (P = 0.010). The 3-year survival rate for the RHCT group was 11.4% and 0% for the CT group (P = 0.018). No difference in grade 3 or 4 adverse events was observed between the two groups (P > 0.05). Multivariate analysis showed that hyperthermia, disease stage, Glasgow prognostic score, and abdominal metastasis were closely associated with the prognosis of these AGC patients.

Conclusion: The study suggests that combination treatment with RHCT for AGC has clinical potential for both short- and long-term curative effects without compromising toxicity.
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http://dx.doi.org/10.1515/med-2019-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401389PMC
February 2019

Intraperitoneal perfusion chemotherapy and whole abdominal hyperthermia using external radiofrequency following radical D2 resection for treatment of advanced gastric cancer.

Int J Hyperthermia 2019 4;36(1):403-407. Epub 2019 Mar 4.

b Department of Oncology, Affiliated Hangzhou First People's Hospital , Zhejiang University School of Medicine , Hangzhou , PR China.

Background: The peritoneum is the most frequent site of disease recurrence in gastric cancer, and the prognosis remains poor. This study assessed the role of adjuvant intraperitoneal (IP) chemotherapy with whole abdominal hyperthermia using external radiofrequency in gastric cancer patients after D2 dissection.

Methods: Patients with gastric cancer who underwent gastrectomy with D2 regional lymph node dissection were enrolled in the study. Patients received IP chemotherapy with whole abdominal hyperthermia. Preheated normal saline containing 75 mg/m of cisplatin was delivered into the abdominal cavity through a Tenckhoff catheter at McBurney's point. Regional hyperthermia was performed using two sets of orthogonal radiofrequency waves immediately after all saline was irrigated into the abdominal cavity. For each patient, recurrent or metastatic sites and adverse events were evaluated.

Results: A total of 22 patients were finally included. All patients tolerated hyperthermia well. Only two patients experienced grade 1 superficial thermal injury. The most frequent grade 3/4 adverse events were myelosuppression, nausea/vomiting, trichomadesis and liver dysfunction. We also found IP chemotherapy with whole abdominal hyperthermia could reduce the total recurrent/metastatic rate, especially peritoneal metastasis (4.5%).

Conclusions: This hypothesis-generating study indicated that IP chemotherapy with whole abdominal hyperthermia might be feasible for gastric cancer patients after D2 resection.
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http://dx.doi.org/10.1080/02656736.2019.1579372DOI Listing
December 2019

Radiation pneumonitis in lung cancer treated with volumetric modulated arc therapy.

J Thorac Dis 2018 Dec;10(12):6531-6539

Department of Oncology, The Fourth Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou First People's Hospital, Hangzhou Cancer Hospital, Hangzhou 310006, China.

Background: Few studies to date have assessed the incidence of radiation pneumonitis (RP) in lung cancer patients who have been treated with volumetric modulated arc therapy (VMAT). This study is aimed at reporting the RP incidence rate and the risk factors associated with a symptomatic RP in patients with lung cancer treated with VMAT.

Methods: A total of 77 consecutive lung cancer patients treated with VMAT from 2013 through 2015 were reviewed. RP severity was graded according to the Common Terminology Criteria for Adverse Events (CTCEA) v.4. Univariate and multivariate analyses were performed to identify the significant factors associated with RP.

Results: VMAT allowed us to achieve most planning objectives on the target volumes and organs at risk, for PTV V =96.8%±3.1%, for lung V =41.3%±8.7%, V =30.0%±7.1%, V =20.9%±5.7%, for heart V =43.2%±29.9%, for esophagus V =8.1%±12.9%. The maximum dose of spinal cord was 34.4±9.5 Gy. The overall incidence of symptomatic RP (grade ≥2 by CTCAE) was 28.6% in the entire cohort, and the rate of grade ≥3 RP was 11.7%. Based on the multivariate analysis, factors predictive of symptomatic RP included lung volume receiving ≥10 Gy (V) (P=0.019) and C-reactive protein changing level (P=0.013).

Conclusions: Our data showed that the incidence rate of RP was acceptable in lung cancer patients treated with VMAT. Additionally, we found that V might be an important factor for predicting the development of RP when VMAT was used; but this observation needs to be validated in future studies.
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http://dx.doi.org/10.21037/jtd.2018.11.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344715PMC
December 2018

ctDNA assessment of EGFR mutation status in Chinese patients with advanced non-small cell lung cancer in real-world setting.

J Thorac Dis 2018 Jul;10(7):4169-4177

Department of Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.

Background: The prevalence of EGFR mutations in circulating free tumor-derived DNA (ctDNA) was still unknown in China. This large-scale study (NCT02623257) aimed to explore the prevalence of epidermal growth factor receptor (EGFR) mutations and determine the correlation of EGFR mutation status with clinical characteristics.

Methods: Plasma DNA samples from 1,001 patients with stage III/IV NSCLC who received ≤1st line chemotherapy were collected from 65 hospitals. EGFR mutations were tested by amplification refractory mutation system (ARMS) method. The EGFR mutation rate was calculated and the associations between EGFR status and patients' demographic data, disease status as well as treatment pattern were explored.

Results: EGFR mutations were detected in 251 of 1,001 (25.1%) patients, 26.8% in adenocarcinoma and 11.7% in squamous carcinoma. A total of 189 harbored sensitizing mutations alone, 28 had resistance mutations alone, 3 had a combination of activating mutations, and 31 had a combination of activating and resistance mutations. Higher detection rate was observed in chemotherapy-naïve patients than those received 1st line chemotherapy (27.0% 18.0%; P=0.006). Of which, the mutation rate of exon 19 deletion was 9.31% for naïve patients and 7.37% for the 1st chemotherapy patients; while the mutation rate of L858R decreased obviously from 10.20% (naïve) to 3.69% (1st line). We also noticed the mutation rate was 37.1% in patients with ≥2 organ metastases. Multivariate analysis showed female, chemotherapy-naïve, or ≥2 metastatic organs patients had higher EGFR mutation rate.

Conclusions: ctDNA based EGFR mutation test is feasible and could be a surrogate when tissue biopsy is not available.
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http://dx.doi.org/10.21037/jtd.2018.06.166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105939PMC
July 2018

Correction to: Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment.

Pathol Oncol Res 2018 10;24(4):951

Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Nanjing, China.

The affiliation of first author (Lucheng Zhu) should be Department of Oncology, Hangzhou Cancer Hospital and Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University.
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http://dx.doi.org/10.1007/s12253-018-0421-9DOI Listing
October 2018

Epidermal growth factor receptor (EGFR) T790M mutation identified in plasma indicates failure sites and predicts clinical prognosis in non-small cell lung cancer progression during first-generation tyrosine kinase inhibitor therapy: a prospective observational study.

Cancer Commun (Lond) 2018 05 22;38(1):28. Epub 2018 May 22.

Center for Translational Medicine, Hangzhou First People's Hospital, Nanjing Medical University, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310006, Zhejiang, China.

Introduction: Plasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients.

Methods: Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF). Amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) were used to identify the T790M mutation in ctDNA. Prognosis was analyzed with Kaplan-Meier methods.

Results: Overall concordance between the two methods was 78.3%. According to both ARMS and ddPCR, patients in the OF group had a significantly higher rate of T790M mutation than did patients in the BF and CF groups (P < 0.001), and a significantly higher T790M mutation rate was also observed in OF-group patients than in those in the CF and BF groups (P < 0.001). AZD9291 was found to be an excellent treatment option and yielded the longest survival for T790M+ patients in all groups who had progressed on EGFR-TKIs; for other treatments, the prognosis of T790M- patient subgroups varied.

Conclusions: The present study demonstrates that T790M mutation in ctDNA is associated with failure sites for NSCLC patients after EGFR-TKI therapy and indicates that both failure site and T790M mutational status greatly influence treatment selection and prognosis.
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http://dx.doi.org/10.1186/s40880-018-0303-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993134PMC
May 2018

S-allylcysteine suppresses ovarian cancer cell proliferation by DNA methylation through DNMT1.

J Ovarian Res 2018 May 14;11(1):39. Epub 2018 May 14.

Hangzhou Translational Medicine Research Center, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, No.261 Huansha Road, Shangcheng District, Hangzhou, 310006, China.

Background: The anti-tumor effects of S-allylcysteine (SAC), a water-soluble garlic derivative, on human ovarian cancer cells have been previous studied in vitro and in vivo models but the precise epigenetic molecular mechanisms are still unclear. This study aimed to investigate the epigenetic mechanism of SAC.

Methods: Human epithelial ovarian cancer cell line A2780 was selected. Cell proliferation and cell cycle was analyzed. DNA methylation, DNA methyltransferase (DNMT) activity, tumor suppressor gene expressions, as well as protein expression were analyzed.

Results: SAC could inhibit the proliferation of A2780 cells in dose- and time-dependent manners (the IC was 16.25 mmol/L and 5.25 mmol/L at 48 h and 72 h). Treatment of A2780 cells with SAC resulted in G1/S phase arrest. SAC treatment decreased global DNA methylation levels in A2780 cells in a dose-dependent manner. SAC decreased the levels of 5-methylcytosine, DNMT activity, messenger RNA (mRNA) and protein levels of DNMT1. Additionally, SAC treatment resulted in re-expression of the mRNA and proteins of silenced tumor suppressor gene CDKN1A accompany with reduced cell division control 2 expression.

Conclusion: Our data indicated the potential therapeutic effects of SAC on the human ovarian carcinoma cell line A2780 in vitro. The epigenetic mechanism of action of SAC may have important implications for epigenetic therapy.
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http://dx.doi.org/10.1186/s13048-018-0412-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952516PMC
May 2018

AZD9291 Increases Sensitivity to Radiation in PC-9-IR Cells by Delaying DNA Damage Repair after Irradiation and Inducing Apoptosis.

Radiat Res 2018 03 13;189(3):283-291. Epub 2018 Jan 13.

b   Department of Oncology, Hangzhou First People's Hospital of Nanjing Medical University, Hangzhou, China.

AZD9291 is a novel, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which is administered orally. It has been proven effective in non-small cell lung cancer (NSCLC) patients, with both EGFR-sensitizing and EGFR T790M mutations in preclinical models. However, the potential therapeutic effects of AZD9291 combined with other modalities, including ionizing radiation, are not well understood. The presence of AZD9291 significantly increases the cell-killing effects of radiation in PC-9-IR cells with a secondary EGFR mutation (T790M), which was developed from NSCLC PC-9 cells (human lung adenocarcinoma cell with EGFR 19 exon 15 bp deletion) after chronic exposure to increasing doses of gefitinib, and in H1975 cells (human lung adenocarcinoma cell with EGFR exon 20 T790M mutation de novo), but not in PC-9 cells or in H460 cells (human lung adenocarcinoma cell with wild-type EGFR). In PC-9-IR cells, AZD9291 remarkably decreases phosphorylation levels of EGFR, extracellular regulated protein kinase (ERK), and protein kinase B (AKT). AZD9291 increases sensitivity to radiation in PC-9-IR cells by delaying deoxyribonucleic acid (DNA) damage repair after irradiation and inducing apoptosis, and enhances tumor growth inhibition when combined with radiation in PC-9-IR xenografts. Our findings suggest a potential therapeutic effect of AZD9291 as a radiation sensitizer in lung cancer cells with an acquired EGFR T790M mutation, providing a rationale for a clinical trial using the combination of AZD9291 and radiation in NSCLCs harboring acquired T790M mutation.
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http://dx.doi.org/10.1667/RR14682.1DOI Listing
March 2018

Role of transcription factor FOXA1 in non‑small cell lung cancer.

Mol Med Rep 2018 Jan 26;17(1):509-521. Epub 2017 Oct 26.

Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China.

In our previous study, stable subpopulations of the A549 lung cancer cell line with high/low invasive potential (H/L‑INV) were obtained. In the present study, microarray analysis of the H/L‑INV A549 subpopulations was performed to evaluate genes associated with high invasiveness. Forkhead box protein A1 (FOXA1) was selected for further investigation. The expression levels of FOXA1 in the primary lesion and metastatic lymph nodes were assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. In addition, the mRNA and protein expression levels of FOXA1 were examined in H‑INV A549 cells transfected with a specific FOXA1 small interfering RNA (siRNA), and the role of FOXA1 in the proliferation, invasion and metastasis of non‑small cell lung cancer (NSCLC) cells was evaluated. FOXA1 was overexpressed in metastatic lymph nodes, compared with its expression in NSCLC primary tumours. The results of western blot and RT‑qPCR analyses confirmed that FOXA1 siRNA transfection led to a decrease in the expression of FOXA1 in H‑INV A549 cells. FOXA1 siRNA transfection caused G0/G1 phase cell cycle arrest, and also reduced the invasion, migration and proliferation abilities of the H‑INV A549 cells. In conclusion, the results of the present study suggested that FOXA1 is a potential oncogene in NSCLC; therefore, specific interference of the expression of FOXA1 may represent a novel approach for the treatment of NSCLC.
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http://dx.doi.org/10.3892/mmr.2017.7885DOI Listing
January 2018

Comparison of the Amplification Refractory Mutation System, Super Amplification Refractory Mutation System, and Droplet Digital PCR for T790 M Mutation Detection in Non-small Cell Lung Cancer after Failure of Tyrosine Kinase Inhibitor Treatment.

Pathol Oncol Res 2018 Oct 3;24(4):843-851. Epub 2017 Sep 3.

Hangzhou First People's Hospital, Nanjing Medical University, No.261, Huansha Road, Shangcheng District, Hangzhou, 310006, People's Republic of China.

Plasma mutation detection has the advantages of non-invasiveness and accessibility. Here, we evaluated three methods, the amplification refractory mutation system (ARMS), second-generation ARMS (SuperARMS), and droplet digital PCR (ddPCR), to assess their concordance and feasibility for the detection of mutations in plasma samples. Non-small lung cancer patients with stage IIIB/IV that were resistant to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment were enrolled. Blood samples were collected within 14 days after TKI resistance. Each sample was simultaneously assessed by the three methods. In total, 169 patients were enrolled; 54.4% were female, 72.2% were diagnosed with stage IV disease; and 97.6% had adenocarcinoma. T790 M mutations were detected in 42 (24.8%) of the 169 samples using ARMS, one of which carried the T790 M alone, 22 that also encoded exon 19 deletions, and 19 with L858R mutations. For the SuperARMS assay, 59 (34.9%) samples exhibited the T790 M mutation, and 110 (65.1%) showed no detectable T790 M mutation. ddPCR showed that 61 (36.1%) samples contained the T790 M mutation, whereas 108 (63.9%) were not positive. T790 M abundance ranged from 0.04% to 38.2%. The median T790 M abundance was 0.15% for total samples and 2.98% for T790 M mutation samples. The overall concordance was 78.7% (133/169) among ARMS, SuperARMS, and ddPCR. Compared with patients with stage III disease, patients with stage IV disease exhibited a higher T790 M mutation detection rate (28.7% vs. 14.9% by ARMS; 37.7% vs. 27.7% by SuperARMS; and 41.8% vs. 21.3% by ddPCR). Liquid biopsy showed promise and has the advantages of non-invasiveness and accessibility. T790 M detection based on circulating tumor DNA showed high concordance. Compared with non-digital platforms, ddPCR showed higher sensitivity and provided both frequency and abundance information, which might be important for treatment decisions.
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http://dx.doi.org/10.1007/s12253-017-0286-3DOI Listing
October 2018

Therapeutical effect of intrapleural perfusion with hyperthermic chemotherapy on malignant pleural effusion under video-assisted thoracoscopic surgery.

Int J Hyperthermia 2018 06 5;34(4):479-485. Epub 2017 Jul 5.

a Hangzhou First People's Hospital, Nanjing Medical University , Hangzhou , PR China.

Background: Patients with malignant pleural effusions (MPEs) have limited life expectancy. This study aims to investigate the feasibility of intrapleural perfusion with hyperthermic chemotherapy (IPHC) under video-assisted thoracoscopic surgery on MPE patients.

Methods: MPE patients were enrolled in the study and treated with IPHC. The treatment response was classified as complete response (CR, no re-accumulation of pleural fluid for 4 weeks), partial response (PR, re-accumulation above the post-IPHC level but below the pre-IPHC level for four weeks), no response (NR; re-accumulation or above the pre-IPHC level). The change of Karnofsky performance score (KPS) and tumour markers were also recorded. Follow-up was done every two weeks during first month and monthly thereafter until death.

Results: Eighty patients included 46 males and 34 females were included in the study. The total response rate was 100%, with 71.3% of CR and 28.7% of PR. The KPS scores were significantly elevated and the level of tumour markers in pleural effusion were dramatically decreased after IPHC. The median survival was 16.8 months ranged from 2.1 to 67.4 months. One-year and two-year survival rates were 82.5% and 23.8%, respectively. There were no serious clinical compilations during IPHC treatment.

Conclusions: IPHC is a safety, effective and promising approach for MPE patients. It provides well survival benefit and minor toxicities.
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http://dx.doi.org/10.1080/02656736.2017.1340676DOI Listing
June 2018

Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells.

Oncotarget 2016 Oct;7(42):68768-68780

Department of Oncology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.

Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.
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http://dx.doi.org/10.18632/oncotarget.11967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356588PMC
October 2016

Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis.

Pathol Oncol Res 2016 Oct 28;22(4):853-61. Epub 2016 May 28.

Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, No.261, Huansha Road, Shangcheng District, Hangzhou, 310006, People's Republic of China.

Fluoropyrimidine-based regimens are the most common treatments in advanced gastric cancer. We used a Bayesian network meta-analysis to identify the optimal fluoropyrimidine-based chemotherapy by comparing their relative efficacy and safety. We systematically searched databases and extracted data from randomized controlled trials, which compared fluoropyrimidine-based regimens as first-line treatment in AGC. The main outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). A total of 12 RCTs of 4026 patients were included in our network meta-analysis. Pooled analysis showed S-1 and capecitabine had a significant OS benefit over 5-Fu, with hazard ratios of 0.90 (95%CI = 0.81-0.99) and 0.88 (95%CI = 0.80-0.96), respectively. The result also exhibited a trend that S-1 and capecitabine prolonged PFS in contrast to 5-Fu, with hazard ratios of 0.84 (95%CI = 0.66-1.02) and 0.84 (95%CI = 0.65-1.03), respectively. Additionally, all the three fluoropyrimidine-based regimens were similar in terms of ORR and grade 3 or 4 AEs. Compared with regimens based on 5-Fu, regimens based on S-1 or capecitabine demonstrated a significant OS improvement without compromise of AEs as first-line treatment in AGC in Asian population. S-1 and capecitabine can be interchangeable according their different emphasis on AEs.
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http://dx.doi.org/10.1007/s12253-016-0078-1DOI Listing
October 2016

Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review.

PLoS One 2016 26;11(5):e0156494. Epub 2016 May 26.

Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, PR China.

Objective: Thoracic radiotherapy (TRT) is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC). However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy.

Materials And Methods: A quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED) and median overall survival (mOS), median progression-free survival (mPFS), 1-, 3-, and 5-year overall survival (OS) as well as local relapse (LR) were evaluated.

Results: In all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001) and the mPFS (R2 = 0.045, p<0.001). The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001). A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001) and the mPFS (p<0.001), improved the 1-, 3-, and 5-year OS (p<0.001) and decreased the rate of LR (p<0.001).

Conclusion: This study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882048PMC
July 2017

Glasgow prognostic score predicts prognosis of non-small cell lung cancer: a meta-analysis.

Springerplus 2016 12;5:439. Epub 2016 Apr 12.

Affiliated Hangzhou Hospital of Nanjing Medical University, No. 261, Huansha Road, Shangcheng District, Hangzhou, 310006 People's Republic of China.

Objective: Glasgow prognostic score (GPS), an inflammation-based scoring system, has been evaluated in various cancers. However, its clinical significance remains unclear in non-small cell lung cancer (NSCLC). Therefore, it is necessary to conduct a meta-analysis to explore the prognostic value of GPS in NSCLC patients.

Methods: A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, and the Cochrane Library. The pooled hazard ratios (HRs) of overall survival (OS) were calculated and compared.

Results: A total of 12 studies comprising 2669 patients were included in this meta-analysis. Compared with GPS 0 group, patients in GPS 1-2 group exhibited a reduced OS with a pooled HR of 1.89 (95 % CI 1.57-2.27, p < 0.001; I (2) = 54 %). Six studies had sufficient data to calculate HRs of OS for GPS 1 and GPS 2 groups. Analysis revealed that GPS 2 group had a statistically significant reduced OS compared with GPS 1 group with a pooled HR of 1.87 (95 % CI 1.18-2.97, p = 0.008; I (2) = 72 %). Study type (retrospective vs. prospective) and disease stage could partially explain the heterogeneity of each study by subgroup analysis.

Conclusion: Pretreatment GPS could serve as a simple and reliable prognosis predictor for NSCLC. More well-designed studies that consider GPS as a stratification factor are warranted.
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http://dx.doi.org/10.1186/s40064-016-2093-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828364PMC
April 2016

Anti-PD-1/PD-L1 Therapy as a Promising Option for Non-Small Cell Lung Cancer: a Single arm Meta-Analysis.

Pathol Oncol Res 2016 Apr 9;22(2):331-9. Epub 2015 Nov 9.

Hangzhou First People's Hospital, No.261, Huansha Road, Shangcheng District, Hangzhou, 310006, People's Republic of China.

Anti-PD-1/PD-L1 antibodies showed satisfactory efficacy in treating non-small-cell lung cancer. We conducted this meta-analysis to explore the advantage subtypes and best therapeutic modalities of Anti-PD-1/PD-L1 therapy on NSCLC. A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, and the Cochrane Library. The pooled ORR, 6-month progression-free survival rate (PFSR6m), and 1-year overall survival rate (OSR1y) were calculated and compared. 15 trials were included in this meta-analysis. Our analyses demonstrated the pooled ORR of 1st line and 2nd or more line anti-PD-1/PD-L1 therapy were 36.5% (21.9-51.0%) and 17.0% (14.3-19.7%), respectively. While the difference was significant (Z = 3.31, p < 0.001). The pooled ORR for non-squamous and squamous cell lung cancer were 18.5% (16.0-21.1%) and 17.9% (14.4-21.5%), respectively. The difference was not significant (Z = 0.27, p = 0.791). The pooled ORR for PD-L1 positive and negative patients were 29.6% (21.6-37.6%) and 13.5% (10.6-16.3%), respectively. The difference was significant (Z = 4.39, p < 0.001). The PFSR6m for PD-L1 positive and negative NSCLC were 50.0% (40.5-62.3%) and 27.0% (19.2-34.7%). The difference was significant (Z = 3.72, p < 0.001). The OSR1y for PD-L1 positive and negative NSCLC were 66.8% (44.8%-88.9%) and 54.0% (32.6-75.3%). The difference was not significant (Z = 0.77, p = 0.441). Anti-PD-1/PD-L1 antibody can serve as a promising treatment option for NSCLC. Patients with positive PD-L1 expression may benefit more from anti-PD-1/PD-L1 therapy. 1st-line anti-PD-1/PD-L1 therapy can be chosen as the best modality. Squamous cell lung cancer also benefit from anti-PD-1/PD-L1 therapy.
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http://dx.doi.org/10.1007/s12253-015-0011-zDOI Listing
April 2016

Long Noncoding RNA MALAT-1 Can Predict Metastasis and a Poor Prognosis: a Meta-Analysis.

Pathol Oncol Res 2015 Sep 10;21(4):1259-64. Epub 2015 Jul 10.

Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical University, No.261, huansha Road, shangcheng District, Hangzhou, 310006, People's Republic of China.

Elevated expression of MALAT-1 was found in various cancers, and correlated with metastasis and prognostic. This meta-analysis collected all relevant articles and explored correlation of MALAT-1 with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS). A quantitative meta-analysis was performed through a systematic search in PubMed, Web of Science, Medline, CNKI, CBM, and the Cochrane Library. The odds ratios (OR) of LNM and DM and hazard ratio (HR) of OS were calculated to assess the association strength. Eight studies with a total of 845 patients were included in the meta-analysis. Six different types of cancer were evaluated, with 2 non-small cell lung cancer (NSCLC), 1 colorectal cancer (CRC), 1 gastric cancer (GC), 2 pancreatic cancer (PC), 1 clear cell renal cell carcinoma (ccRCC), and 1 osteosarcoma (OSA). Compared with low MALAT-1 expression, high MALAT-1 expression correlated with more LNM (OR = 2.08, 95 %CI: 1.00-4.32, p = 0.05) by a random-effects model (I (2) = 71 %, p = 0.004). A similar result was seen between MALAT-1 expression and DM, the OR was 3.52 (95 %CI: 1.06-11.71, p = 0.04) adopting a random-effects model (I (2) = 59 %, p = 0.04). Additionally, our analysis showed a poorer OS in patients with high MALAT-1 expression than those with low MALAT-1 expression (HR = 2.12, 95 %CI: 1.60-2.82, p < 0.001) adopting a random-effects model (I (2) = 56 %, p = 0.04). MALAT-1 may serve as a molecular marker for cancer metastasis and prognosis.
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http://dx.doi.org/10.1007/s12253-015-9960-5DOI Listing
September 2015

HDAC inhibitors: a new radiosensitizer for non-small-cell lung cancer.

Tumori 2015 May-Jun;101(3):257-62. Epub 2015 May 1.

1 Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou - PR China.

For many decades, lung cancer has been the most common cancer and the leading cause of cancer death worldwide. More than 50% of non-small-cell lung cancer patients receive radiotherapy (alone or in combination with chemotherapy or surgery) during their treatment. The intrinsic radiosensitivity of tumors and dose-limiting toxicity restrict the curative potential of radiotherapy. Histone deacetylase inhibitors (HDACis) are an emerging class of agents that target histone deacetylase and represent promising radiosensitizers that affect various biological processes, such as cell growth, apoptosis, DNA repair, and terminal differentiation. Histone deacetylase inhibitors have been found to suppress many important DNA damage responses by downregulating proteins in the homologous recombination and nonhomologous end joining repair pathways in vitro. In this review, we describe the rationale for using HDACis as radiosensitizers and the clinical evidence regarding the use of HDACis for the treatment of non-small-cell lung cancer.
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http://dx.doi.org/10.5301/tj.5000347DOI Listing
September 2015

Primary anorectal malignant melanoma treated with neoadjuvant chemoradiotherapy and sphincter-sparing surgery: A case report.

Oncol Lett 2014 May 28;7(5):1605-1607. Epub 2014 Feb 28.

Department of Radio-Chemotherapy Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Primary anorectal (PA) malignant melanoma (MM) is a rare disease associated with a high mortality rate. The most appropriate treatment strategy for PAMM remains controversial. A 55-year-old female patient, who was misdiagnosed with locally advanced rectal carcinoma, was treated with preoperative radiotherapy and concurrent oral capecitabine. During the therapy, grade 1 leukopenia occurred, however, there was no interruption to treatment. Following chemoradiotherapy, a computer tomography scan identified that the tumor had shrunk significantly and the original enlarged lymph nodes had disappeared. Eight weeks after completion of chemoradiotherapy, sphincter-sparing surgery was performed on the patient and based on the postoperative pathological result, MM was diagnosed. At the time of writing, the patient has survived disease-free for 15 months and at the most recent follow-up examination the Karnofsky Performance Scale score was 100. The therapeutic regimen of neoadjuvant concurrent chemoradiotherapy together with sphincter-sparing surgery is considered to be an optimal choice for patients with PAMM. However, further studies are required to evaluate the efficacy and clinical utility of this therapeutic regimen.
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http://dx.doi.org/10.3892/ol.2014.1925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997679PMC
May 2014

Comparison between artificial neural network and Cox regression model in predicting the survival rate of gastric cancer patients.

Biomed Rep 2013 Sep 18;1(5):757-760. Epub 2013 Jul 18.

Department of Radio-Chemotherapy Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325002, P.R. China.

The aim of this study was to determine the prognostic factors and their significance in gastric cancer (GC) patients, using the artificial neural network (ANN) and Cox regression hazard (CPH) models. A retrospective analysis was undertaken, including 289 patients with GC who had undergone gastrectomy between 2006 and 2007. According to the CPH analysis, disease stage, peritoneal dissemination, radical surgery and body mass index (BMI) were selected as the significant variables. According to the ANN model, disease stage, radical surgery, serum CA19-9 levels, peritoneal dissemination and BMI were selected as the significant variables. The true prediction of the ANN was 85.3% and of the CPH model 81.9%. In conclusion, the present study demonstrated that the ANN model is a more powerful tool in determining the significant prognostic variables for GC patients, compared to the CPH model. Therefore, this model is recommended for determining the risk factors of such patients.
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http://dx.doi.org/10.3892/br.2013.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917700PMC
September 2013

High efficacy of combination chemotherapy with S-1 and low-dose docetaxel for the treatment of highly advanced gastric cancer with peritoneal dissemination: A case report.

Oncol Lett 2013 May 8;5(5):1509-1512. Epub 2013 Mar 8.

Department of Radio-Chemotherapy Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325035, P.R. China.

S-1 has been developed as a new oral anticancer drug based on the biological modulation of 5-fluorouracil. We treated a patient with highly advanced gastric carcinoma with a new combination chemotherapy of S-1 and low-dose docetaxel. Evident tumor reduction was observed following two cycles of this therapy in the primary tumor and metastatic lymph nodes. This was concluded to be a partial response. The gastric tumor exhibited significant invasion to the serosa. Lymph nodes around the stomach were swollen. Peritoneal dissemination was also identified in the mesocolon. Palliative resection of part of the distal stomach and dissection of regional lymph nodes were performed. Histological examination demonstrated that no tumor cells were detected in the greater omentum, suggesting pathological complete remission. It is suggested that this regimen may provide a potent combined therapy for the treatment of patients with highly advanced gastric carcinoma and it may be useful as an adjuvant chemotherapy. Further studies are necessary to evaluate the efficacy of this therapy.
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http://dx.doi.org/10.3892/ol.2013.1237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678634PMC
May 2013