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Objective:To study the combined use of neoadjuvant chemotherapy and immunotherapy in patients with borderline resectable pancreatic cancer.Methods:The clinical data of patients with pancreatic cancer who were planned to undergo perioperative treatment before surgical treatment at the Fifth Medical Center of PLA General Hospital from January 2019 to June 2021 were retrospectively studied. Of 22 patients with pancreatic cancer, there were 10 males and 12 females, aged (56.0±10.2) years old. Preoperative treatment with chemotherapy (nab-paclitaxel and S-1, AS) and immunotherapy regimen before surgery were given. The baseline characteristics, treatment efficacy, surgical pathology and prognosis were analyzed.Results:Of 22 patients who were treated with neoadjuvant chemotherapy combined with programmed death-1 (PD-1) monoclonal antibody, 11 patients (50%) had tumors in the head, neck and uncinated process of pancreas. On radiographic assessment, one patient achieved CR (4.5%, 1/22), 9 patients PR (40.9%, 9/22), and 11 patients SD (50.0%, 11/22). All patients subsequently underwent R 0 resection. The postoperative pTNM staging showed 91% (20/22) of patients were in stage IA-IIB, 31.8% (7/22) of patients had pT2, 63.6% (14/22) had N0, and 1 patient had pCR. Thirteen patients (54.2%, 13/22) received postoperative adjuvant therapy. The median recurrence-free survival (RFS) was 6.4 months and the median time to progression (TTP) was 12.8 months. The median overall survival of patients was not reached. Postoperative pathology TNM staging IIA to III ( HR=3.63, 95% CI: 1.18-11.20, P=0.025) and postoperative pathology T2-3 stage ( HR=2.02, 95% CI: 1.01-5.05, P=0.049) were significantly associated with RFS. Postoperative pathology TNM stages IIA to III ( HR=2.39, 95% CI: 1.04-5.50, P=0.041) and postoperative pathology T2-3 stage ( HR=2.53, 95% CI: 1.26-5.09, P=0.009) were significantly associated with TTP. Conclusion:AS combined with PD-1 monoclonal antibody showed good efficacy as a neoadjuvant therapy for patients with borderline-resectable pancreatic cancer.
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BACKGROUND@#Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear.@*METHODS@#To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification.@*RESULTS@#PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs.@*CONCLUSIONS@#As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.
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Animals , Humans , Mice , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Epithelial Cells/metabolism , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Gene Expression Regulation, Neoplastic , PAX5 Transcription Factor/genetics , Tumor Suppressor Protein p53/genetics , Xenograft Model Antitumor AssaysABSTRACT
Objective:To evaluate the efficacy of preoperative neoadjuvant chemoradiotherapy for low and locally advanced rectal cancer.Methods:Clinical data of 46 patients with low rectal tumors located within 6 cm from the edge of anal admitted to our hospital between February 2014 and December 2018 were retrospectively analyzed. SIB-IMRT technique was adopted for preoperative radiotherapy. Rectal tumors and positive lymph nodes were irradiated with a dose of 58.75 Gy in 25 fractions (2.35 Gy/fraction), and pelvic lymphatic drainage area was given with 50 Gy in 25 fractions (2.0 Gy/fraction). Oral administration of capecitabine was delivered for concurrent chemotherapy. Radical surgery for rectal cancer was performed at 6 to 12 weeks after the end of chemoradiotherapy. The overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), local recurrence-free survival (LRFS) and metastasis-free survival (MFS) were calculated by using Kaplan- Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox’s regression model. Results:After a median follow-up of 47 months, local recurrence occurred in 3 patients and distant metastasis in 6 patients. The ypCR rate was 26%(12/46), the sphincter-preservation rate was 74%(34/46), the R 0 resection rate was 100%(44/44), the overall tumor response TN down staging rate was 87%(40/46), and the postoperative complication rate was 13%(6/46). The 3-year OS, DFS, and PFS were 93%, 91% and 87%, respectively. In univariate analysis, ypN staging was an important factor affecting OS, DFS, PFS, LRFS and MFS (all P<0.05). In multivariate analysis, ypN staging was significantly correlated with DFS, PFS, LRFS and MFS (all P<0.05). Conclusions:Preoperative SIB-IMRT 58.75 Gy in 25 fractions combined with capecitabine chemotherapy is a safe and efficacious treatment for patients with low and locally advanced rectal cancer, which improves the ypCR rate and quality of life, and yields tolerable adverse reactions. Nevertheless, the long-term survival benefits remain to be validated.
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Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.
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Objective To evaluate the feasibility and clinical efficacy of preoperative simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with neoadjuvant chemotherapy of capecitabine in patients with locally-advanced low rectal cancer.Methods Between 2015 and 2016,26 patients admitted to 301 Hospital who were diagnosed with locally-advanced low rectal cancer,which was located within 5 cm from the anal verge,were enrolled in this investigation.Dose fractionation pattern was delivered:58.75 Gy in 25 fractions (2.35 Gy/fraction) for rectal cancer and lymph node metastasis and 50 Gy in 25 fractions for the pelvic lymphatic drainage area and simultaneously combined with capecitabine chemotherapy (825 mg/m2,bid d 1-5 weekly).One cycle of capecitabine (1 250 mg/m2,twice daily,d 1-14)was given at one week after the completion of chemoradiotherapy (CRT).Total mesorectal excision (TME)was performed at 6 to 8 weeks after the completion of CRT.The primary endpoints included pathological complete response rate (ypCR) and sphincter-preserving rate.The secondary endpoints included acute toxicity,tumor downstaging rate and postoperative complications.Results Twenty-six patients successfully completed neoadjuvant CRT,25 of them underwent surgical resection and one patient failed to receive surgery due to pxrianal edema.Postoperative ypCR rate was 32％ (8/25),the sphincter-preserving rate was 60％ (15/25),the tumor downstaging rate was 92％ (23/25) and the R0 resection rate was 100％.During the period of CRT,grade 1 and 2 adverse events occurred in 24 patients,grade 3 radiation dermatitis was noted in 2 cases.No ≥ grade 4 acute adverse event was observed.Postoperative complications included ureteral injury in one case and intestinal obstruction in one patient.Conclusions Preoperative SIB-IMRT combined with neoadjuvant chemotherapy of capecitabine is a feasible and safe treatment for patients with locallyadvanced low rectal cancer,which yields expected ypCR rate,R0 resection rate and sphincter-preserving rate.Nevertheless,the long-term clinical benefits remain to be elucidated.Clinical Trial Registry Chinese Clinical Trial Registry,registration number:ChiCTR-ONC-12002387.
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Objective: To evaluate the prognostic value of chemotherapy-induced neutropenia (CIN) in metastatic colon cancer undergoing first-line chemotherapy with FOLFOX.Methods: Data were collected from a retrospective survey of 158 consecutive metastatic colon cancer patients who had undergone FOLFOX chemotherapy.The clinicopathological characteristics and chemotherapy features of the patients were analyzed as potential prognostic factors.The patients were stratified by the decreased level of CIN to three groups: large decreased level (the number of neutrophil decreased more than 1.0×109 compared with that before chemotherapy),small decreased level (the number of neutrophil decreased less than 1.0×109 compared with that before chemotherapy) and the absence of neutropenia.Results: According to a multivariate COX model, decreased level of CIN was a independent prognostic factor of colon cancer patients.Hazard ratios of death were 0.687 (95% CI: 0.381-0.812, P=0.016) for patients with large decreased level of CIN and 0.817 (95% CI: 0.527-0.939,P=0.027) for those with small decreased level of CIN compared with those of absent neutropenia patients.Median overall survival was 12.9 months (95% CI: 10.4-15.4) for patients without neutropenia (A) compared with 20.8 months (95% CI: 18.3-23.1) for patients with large-decreased level of CIN (L) and with 17.3 months (95% CI: 16.2-18.8) for those with small-decreased level of CIN (S vs.L, P=0.018;L vs.A, P=0.009;S vs.A, P=0.011).Conclusion: Our results demonstrate that the decreased level of CIN is a predictor of prognosis in patients with metastatic colon cancer undergoing FOLFOX chemotherapy.Patients who have experienced large decreased level of CIN haave longer survival time than small decreased level of CIN or absent patients.To monitor CIN decreased level timely and adjust chemotherapy drug dose may help improve the prognosis.
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Colonic neoplasms is the third most commonly diagnosed cancer in men and second most commonlv diagnosed cancer in women worldwide.The morbidity of Colonic neoplasms is increasing year by year.Despite the fact that surgery is still the main treatment for patients with colon cancer,surgery alone hasn't improved the treatment effectiveness.The current management of colon cancer has come to multidisciplinary team (MDT) modality.MDT modality could offer the optimal treatment option and the internal communication.Under the pattern of MDT which integrates the surgery,chemotherapy,radiotherapy,interventional therapy,targeted therapy and immune therapy,there has been a big progress in the diagnosis and treatment of colon cancer.Patients with metastatic colon cancer should undergo a discussion by a multidisciplinary team before the initial treatment.
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Hypoxia plays a vital role in tumor metabolism, proliferation, apoptosis, invasion and metastasis via hypoxia-inducible factor (HIF). Epithelial to mesenchymal transition (EMT) is a crucial process to metastasis, which could be triggered by hypoxia. EMT could be regulated by HIF via multiple pathways including TGF-β, Notch, and Wnt/β-catenin. It has been shown that anti-HIF drugs combined with anti-EMT therapies could be a promising strategy for tumor therapy.
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Humans , Basic Helix-Loop-Helix Transcription Factors , Epithelial-Mesenchymal Transition , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasms , Transforming Growth Factor beta , beta CateninABSTRACT
Objective To investigate the effects of gemcetabine and LY294002 monotherapy or combination on the proliferation and poptosis of pancreatic cancer cell lines BxPc-3 and MiaPaCa-2.Methods Cell proliferation and poptosis were detected by MTT and Annexin V-FTTC,respectively.Results Both gemcetabine and LY294002 could inhabit the proliferation of the two cell lines.Their inhibitory effects were increased accompanied with increased drug concentrations and the cell survival rates was negatively correlated with logarithmic of the drug concentrations (r＜-0.95,P＜0.01).The inhibitory effects of gemcetabine and LY294002 to the BxPc-3 proliferation were significantly stronger than to the MiaPaCa-2(P＜0.05).For BxPc-3 and MiaPaCa-2,the IC50 of gemcetabine were(10.07±1.83),(36.45±2.71)μmol/L(P＜0.05),and the IC50 of LY294002 were(7.84±1.48),(17.89±1.98)μmol/L(P＜0.05),respectively.Gemcetabine and LY294002 could induce cell apoptosis(P＜0.01).Though both the concurrent or consecutive use of these two drugs could promote cell apoptosis,the effect of the concurrent group was significantly stronger(P＜0.05).The order of these two drugs in the concurrent group had no significant influence on their effects(P＞0.05).Conclusion Both gemcetabine and LY294002 could inhibit the proliferation of pancreatic cancer cell lines.Their concurrent application shows a significant inhibitory effect on the cell apoptosis.
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Objective: To evaluate the efficacy and tolerability of rhGM-CSF in prevention of neutropenia caused by chemothera- py of cancer patients. Methods: A muticenter, randomized,match and crossover clinical study was conducted. 64 enrolled patients were randomized into AB and BA groups and each patient received two cycles of combination chemotherapy.Results:59 patients were evaluted for clinical efficacy.rhGM-CSF significantly increased the number of WBC and ANC at the stage of nadir. The period when the patients, rhGM-CSF also resulted in a hastening recovery from leucopenia and neutropenia.Conclusion: The administraton of rhTM-CSF ensures the implement of sheduled combination chemotherapy. The main side effects such as fever, osteomyalgia,skin rash were generally tolerable.
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Objective To investigate the expression of p16 gene in malignant mesothelioma,and its relationship with histological types,clinical stages and prognosis.Methods Immunohistochemical staining was used to detect the expression of p16 gene in the specimens of 80 cases of malignant mesothelioma.Results The positive expression of p16 gene was found in 35% malignant mesothelioma specimens,and negative in 65%(P
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Expression of the GST-? in 51 cases of lung cancer was researched by quantitative RT-PCR. The results suggested that the expression of GST-? was significantly higher in lung cancer than in normal tissues adjacent to cancer, and tumoral native resistance might be dominant in tumoral resistance to chemotherapeutic drugs. No relationship was found between GST-? expression and clinicopathological parameters including tumor class, stage and differentiation. The study of GST-? expression is of importance in the evaluation of tumoral resistance to anticancer drugs.
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Objective To study the inhibitory effect of ibandronate(IBN)on the growth of lung cancer cell line PLA-801D in vitro,and the mechanism of such effect was studied.Methods The effects of different doses or treatment time of IBN on the growth of PLA-801D cell line were detected by MTT method.The mechanism of the effect was analyzed by the examination of cell cycle using flow cytometry.Results With the concentration of 10 to 100 ?g/ml,IBN obviously inhibited the growth of PLA-801D cell(P