1.Chemotherapy and comparison of agents for advanced duodenal carcinoma
Junbao LIU ; Chengxu CUI ; Jinwan WANG ; Yurong ZHANG ; Nan WANG ; Wei LIU ; Chunhui GAO ; Shuping SHI ; Haijian TANG ; Zhujun SHAO ; Tingting YANG
Chinese Journal of Clinical Oncology 2014;(5):319-323
Objective:This study aims to determine the efficacy of chemotherapy and to identify potential chemotherapy agents for advanced primary duodenal carcinoma (PDC). Methods:Fifty-six patients with advanced PDC, who did and did not receive chemo-therapy, were involved in this study. Response rates (RR), disease control rates (DCR), progression-free survival (PFS), and overall sur-vival (OS) were analyzed. Results:The overall RR and DCR of 43 patients were 19.04%and 71.42%, respectively. The patients who re-ceived chemotherapy agents fluorourzcil and oxaliplatin exhibited higher RR compared with patients who received other chemotherapy combinations (35.29%vs. 7.69%, P=0.010 9). Palliative chemotherapy improved the OS of patients with advanced PDC compared with patients who did not receive chemotherapy (13.35 months vs. 5.65 months, HR=0.203, 95%CI:0.083 to 0.497, P=0.000 5). Compared with the use of other chemotherapy regimens, treatment with a fluorourzcil-based chemotherapy agent resulted in a longer PFS (5.08 months vs. 1.08 months, HR=0.004, 95%CI:0.000 to 0.315, P=0.013 2). Multivariate analysis indicated mucinous histology and lymph mode metastasis as factors predictive of poor prognosis in patients with advanced PDC. Conclusion:Palliative chemotherapy may im-prove the OS of patients with advanced PDC.
2.Chemotherapy for metastatic colorectal cancer after failure of treatment with irinotecan and oxaliplatin
Junbao LIU ; Yurong ZHANG ; Tao QU ; Shuping SHI ; Zhujun SHAO ; Tingting YANG ; Haijian TANG ; Nan WANG ; Wei LIU ; Chunhui GAO ; Chengxu CUI
Chinese Journal of Clinical Oncology 2013;(23):1464-1467
Objective:This retrospective study aims to determine the efficacy of chemotherapy and improve a salvage chemother-apy agent for metastatic colorectal cancer (MCRC) after failure of treatment with irinotecan and oxaliplatin. Methods:Between Janu-ary 2002 and March 2013, 37 patients with metastatic MCRC who had progressed after treatment with irinotecan and oxaliplatin were analyzed for their response rate (RR) and progression-free survival (PFS). Results:The overall RR of the 37 patients was 13.51%, with 5 cases of partial response (PR), 12 cases of disease stabilization (SD), and 20 cases of progression (PD). Compared with other chemo-therapy regimens, treatment with a pemetrexed-based chemotherapy agent had a higher RR (17.64%vs. 10.00%, P=0.64) without a lon-ger PFS (2.00 months vs. 1.63 months, HR=0.79, 95%, CI:0.35 to 1.78, P=0.58). Compared with other chemotherapy regimens, treat-ment with a raltirexed-based chemotherapy agent had a higher RR (16.67%vs. 12.00%, P=0.34) without a longer PFS (1.58 months vs. 1.90 months, HR=2.24, 95%, CI:0.98 to 5.12, P=0.06).Conclusion:In patients with MCRC after failure of treatment with irinotecan and oxaliplatin, a pemetrexed-based or raltirexed-based chemotherapy agent may beneficial during salvage treatment and is therefore worthy of further study.
3.Inhibitory effect of mucopolysaccharide polysulfate cream on hypertrophic scar formation in a rabbit ear model and its mechanisms of action
Yan JING ; Wenmin FEI ; Chengxu LI ; Yong CUI
Chinese Journal of Dermatology 2022;55(8):720-726
Objective:To investigate the inhibitory effect and mechanisms of action of mucopolysaccharide polysulfate cream on hypertrophic scar formation.Methods:Circular full-thickness wounds with a diameter of 6 mm were made in both ears of 16 New Zealand white rabbits to establish a rabbit ear model of hypertrophic scar. There were 3 hypertrophic scars in each rabbit ear. About 14 days after the operation, scars on the left ear were topically treated with mucopolysaccharide polysulfate cream, and served as the experimental group; scars on the right ear were topically treated with the cream vehicle, and served as vehicle control group. The dosage of topical agents for one rabbit ear was approximately 0.4 g, which were given twice a day for 6 consecutive weeks. Scar tissues were collected on days 0, 14 and 42, that is, 14, 28 and 56 after operation respectively, and subjected to hematoxylin and eosin (HE) staining, Masson staining and immunohistochemical study, so as to evaluate histopathological scores, measure the scar thickness and collagen fiber density, and determine the expression of type Ⅰ and Ⅲ collagen and the ratio of type Ⅰ/Ⅲ collagen. The t test and one-way analysis of variance were used to compare the indices between groups. Results:Compared with pretreatment histopathological manifestations, HE staining showed extensive extracellular matrix deposition, inflammatory cell infiltration and local hyperemia in the control group after 42-day treatment, but no obvious changes in the experimental group. The pathological scores of scar tissues on the rabbit ears significantly increased over time in the control group (days 0, 14 and 42: 4.16 ± 1.61, 6.50 ± 1.46, 6.53 ± 1.34, respectively; F = 13.69, P = 0.001) , while there was no significant change in the experimental group (days 0, 14 and 42: 4.65 ± 1.52, 5.13 ± 1.83, 5.38 ± 1.60, respectively; F = 0.78, P > 0.05) . Masson staining showed extremely high content of dark blue-dyed collagen fibers in the control group on day 42, but there was a decrease in the content of collagen fibers in the experimental group; with the increase in treatment duration, the thickness of scar tissues significantly increased in the control group compared with that before treatment ( F = 5.64, P = 0.007) , while there was no significant change in the experimental group ( F = 1.48, P > 0.05) . Immunohistochemical study revealed no significant change in the expression of type Ⅲ collagen in either the experimental group or the control group at any of the above posttreatment time points compared with that on day 0 ( F = 0.22, 0.92, respectively, both P > 0.05) , but the expression of type Ⅰ collagen and the ratio of type Ⅰ/Ⅲ collagen significantly increased in the control group ( F = 7.47, P < 0.001; F = 4.70, P = 0.005, respectively) . On day 42, the expression of type Ⅰ collagen and the ratio of type Ⅰ/Ⅲ collagen significantly decreased in the experimental group compared with the control group ( t = 3.04, P = 0.007; t = 2.35, P = 0.030, respectively) . Conclusion:Topical mucopolysaccharide polysulfate cream is effective in preventing and inhibiting scar hypertrophy by reducing the scar thickness and inhibiting the collagen fiber hyperplasia and type I collagen expression.
4.FOLFOX/XELOX plus cetuximab administered weekly versus biweekly as a first-line treatment for patients with KRAS/RAS wild-type metastatic colorectal cancer: a retro-spective study
Yue YU ; Wen ZHANG ; Yongkun SUN ; Lin YANG ; Chengxu CUI ; Yixin ZENG ; Aiping ZHOU
Chinese Journal of Clinical Oncology 2018;45(23):1210-1214
To compare the efficacy and safety of cetuximab biweekly regimen with those of standard weekly regimen as a first-line therapy of KRAS/RAS wild-type metastatic colorectal cancer. Methods: Patients who received weekly or biweekly administra-tion of cetuximab plus FOLFOX/XELOX as a first-line therapy from July 2010 to December 2017 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively screened for eligibility. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and frequencies of adverse events (AEs) between the two groups were compared. Results: Of 152 eligible patients, 55 were in the biweekly group and 43 were in the weekly group. The biweekly group had significantly higher ORR than the weekly group (76.3% vs. 54.8%, P=0.025). Median PFS in the biweekly and weekly groups were 10.3 and 8.8 months, respectively (P=0.288), and the median OS were 33.5 and 27.4 months, respectively (P=0.563). The two groups showed no significant difference in PFS and OS. For overall AEs, the biweekly group presented significantly more stomatitis (32.7% vs. 14.0% , P=0.032) and tended to show substantially more acne-like rash (80.0% vs. 62.8%, P=0.058) and leukopenia and/or neutropenia (72.7% vs. 55.8%, P=0.081). The frequency of 3/4 grade acne-like rash in the biweekly and weekly groups were 18.2% and 7.0%, respectively (P=0.105). The frequency of all grade 3/4 AEs between the two groups showed no significant difference (P>0.05). Conclusions: Biweekly regimen of cetuximab plus FOLFOX/XE-LOX had similar efficacy and higher ORR compared with those of standard weekly regimen. Cetuximab administered biweekly may be an optional choice in clinical practice, with close attention paid to increased frequency of certain AEs.
5. Biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma
Liangze ZHANG ; Weiwei LI ; Chengxu CUI ; Hongtu ZHANG ; Yan SONG ; Yousheng MAO ; Jing HUANG
Chinese Journal of Oncology 2017;39(3):216-219
Objective:
To evaluate the feasibility and efficacy of biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma.
Methods:
We retrospectively analyzed the clinicopathological data of 20 patients with esophageal squamous cell carcinoma treated in our hospital between January 2012 and March 2016. All patients received biweekly paclitaxel and platinum chemotherapy followed by surgery.
Results:
20 cases received preoperative chemotherapy for 3-8 cycles with an average of 4 cycles. The main chemotherapy-related adverse events were bone marrow suppression (18/20, 90.0%), followed by vomiting and nausea (10/20, 50.0%). Five patients (25.0%) had grade 4 neutropenia and all toxicities were torlerable and manageable. After chemotherapy, all patients received surgery. The histological responses in the primary tumors were grade 1 in 13 (65.0%) patients, grade 2 in 7 (35.0%) patients, and grade 3 in 0 (0%) patient. None had disease progression. Downstaging of T-stage was observed in 5 cases (25.0%) after chemotherapy. Among them, 4 cases were with moderate histologicl responses and one case with mild histological response. The incidence of postoperative complications was 25.0%(5/20), and the complications were improved following symptomatic treatments. There was no treatment-related death.
Conclusions
Biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma is safe and effective. Further randomized clinical trial should be conducted to assess the value of this therapeutic regimen in the preoperative chemotherapy for esophageal cancer.
6.Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle.
Keke LI ; Jingkai XU ; Ke XUE ; Ruixing YU ; Chengxu LI ; Wenmin FEI ; Xiaoli NING ; Yang HAN ; Ziyi WANG ; Jun SHU ; Yong CUI
Chinese Medical Journal 2022;135(4):447-455
BACKGROUND:
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.
METHODS:
Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).
RESULTS:
TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.
CONCLUSION
TPCN2 might be a potential protective factor against SLE.
Apoptosis/genetics*
;
Cell Division
;
Humans
;
Jurkat Cells
;
Lupus Erythematosus, Systemic/genetics*
;
RNA, Small Interfering/genetics*