1.Expression of CDKN3 in tumors and its correlation with prognosis
Bangjie Chen ; Xinyi Wang ; Yipin Yang ; Haiwen Li ; Wei Shao ; Kangsheng Gu
Acta Universitatis Medicinalis Anhui 2024;59(11):1944-1957,1966
Objective:
To investigate the expression changes of cyclin-dependent kinase inhibitor 3(CDKN3) indifferent tumors and its effect on tumor staging, prognosis and immunotherapy.
Methods:
The expression characteristics of CDKN3 in different cancers using data from TCGA, CCLE, ICGC, and GTEx databases were evaluated. The GEPIA2 platform and Kaplan-Meier analysis were utilized to assess the effect of CDKN3 on tumor pathological staging and survival prognosis. The TIMER platform was employed to explore the influence of CDKN3 on the tumor immune microenvironment and immunotherapy. Its effect on immune checkpoint and key immunotherapeutic predictors using bioinformatics methods was explored. The GeneMANIA tool was used to construct the protein-protein interaction(PPI) network of CDKN3. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Onotology(GO) enrichment analyses were conducted to explore the biological processes and signaling pathways associated with CDKN3. The effect of CDKN3 on HepG2 cell proliferation, invasion, migration, and apoptosis was validated through transfection with CDKN3 siRNA.
Results:
CDKN3 was found to be widely overexpressed in tumors. High expression of CDKN3 was often associated with advanced pathological staging and poor survival prognosis. CDKN3 expression was negatively correlated with most immune checkpoints and positively correlated with tumor mutation burden(TMB), microsatellite instability(MSI), and mismatch repair(MMR) genes. CDKN3 was associated with cell cycle, cellular senescence, and the p53 signaling pathway. Furthermore, EdU staining, JC-1 staining, Transwell, and Wound Healing assays confirmed that CDKN3 promoted HCC cell proliferation, invasion, and migration while inhibiting apoptosis.
Conclusion
Abnormal expression of CDKN3 is closely related to tumor staging, prognosis, and immune microenvironment characteristics, making it a potential prognostic marker and immunotherapy adjuvant target in cancer.
2. Clinical efficacy and safety of paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer
Chenchen ZHAO ; Wei WEI ; Kangsheng GU
Chinese Journal of Primary Medicine and Pharmacy 2019;26(12):1450-1453
Objective:
To compare the treatment effect and adverse reaction of oxaliplatin and tiggio and paclitaxel or docetaxel combined with oxaliplatin or cisplatin and fluorouracil or tiggio in the treatment of advanced gastric cancer.
Methods:
From January 2015 to April 2018, 60 patients with advanced gastric cancer were selected from Department of Oncology of the First Affiliated Hospital of Anhui Medical University.The patients were randomly divided into two groups according to the principle of simple randomization, with 30 cases in each group.The control group was treated with oxaliplatin + tiggio.The observation group was given paclitaxel (or docetaxel) combined with oxaliplatin (or cisplatin) and fluorouracil.The incidence of adverse reactions(hematotoxicity and non-hematologic toxicity), the efficacy(CR, PR, SD, PD) of the two groups were compared.
Results:
The RR level of the observation group was 66.7%, which was significantly higher than 40.0% of the control group (χ2=4.286,
3.Influence of different chemotherapeutic drugs combined with oxaliplatin on living quality and serum related tumor markers in gastric cancer patients with postoperative recurrence and metastasis
Yi WANG ; Kangsheng GU ; Baolong WANG
Chongqing Medicine 2017;46(27):3795-3797
Objective To study the influence of capecitabine or S-1 combined with oxaliplatin on the quality of life and serum tumor marker in gastric cancer patients with postoperative recurrence and metastasis.Methods One hundred and six cases of postoperative recurrence and metastasis treated by gastric cancer radical operation in our hospital from January 2013 to December 2015were selected and divided into the control group and observation group according to the random number table method,53 cases in each group.The control group was given S-1 combined with oxaliplatin treatment,while the experimental group was given capeeitabine combined with oxaliplatin treatment.The clinical efficacy,quality of life,serum related tumor markers and adverse reactions were compared between the two groups.Results The effective rate was 64.15% in the control group and 69.81% in the observation group,the difference was not statistically significant (P<0.05).The improvement rate of the quality of life in the control group was 73.58%,the stability rate was 18.87% and decline rate was 26.42%,the total improvement rate was 73.58%,which in the observation group were 49.06 %,20.75 %,30.19 % and 69.81 % respectively,the differences were not statistically significant (P>0.05).After treatment,the levels of CA50,CA125,CA199 and CEA in the two groups were significantly decreased compared with before treatment (P<0.05),but the serum related tumor markers had no statistically significant difference between the two groups (P>0.05).The common adverse reactions in the two groups included hemoglobin decrease,white blood cell decline,thrombocytopenia,nausea and vomiting,the two groups could be tolerated,the difference was not statistically significant (P>0.05).Conclusion Capecitabine or S-1 combined with oxaliplatin has the same curative effect in treating postoperative recurrence and metastasis after gastric cancer operation,the improvement of quality of life and serum related tumor indicators is similar,and the adverse reactions could be tolerated.
4.Research of microRNAs and tumor platinum-resistance
Xiaoli WEI ; Kangsheng GU ; Mengru GAO
Chinese Pharmacological Bulletin 2017;33(5):593-597
Chemotherapy is one of the primary treatment for malignant tumors.Platinum drugs as the most commonly used cycle non-specific clinical antitumor drugs show good curative effect in the clinical treatment of solid tumors,however,resistance or cross-resistance of theplatinum analogous has become one of the main obstacles for platinum and its analogous,which limits their clinical applications.miRNAs play an important role in biology,including cell proliferation,differentiation,apoptosis,stress tolerance,and physiological metabolism.There is a close relationship between miRNAs target gene regulation and tumor drug-resistance.This article is mainly about the role of miRNAs in tumor of platinum resistance.
5.Clinical prognosis with 71 thymic carcinoma patients
Ling XU ; Xinghao AI ; Kangsheng GU
Acta Universitatis Medicinalis Anhui 2015;50(9):1319-1322
Objective To explore the prognostic factor by analyzing clinical characters, pathologic features and treatment methods of thymic carcinoma. Methods From January 2000 to Deceber 2011, 71 patients received re-section of thymic carcinoma. They were analyzed retrospectively based on Masaoka stage(stageII 7,stageIII 33, stageIV 31). The clinical factors included histological classification, Masaoka stage, treatment and prognosis. Sur-vival rate was calculated and the survival curve was plotted by Kaplan-Meimer and Log-Rank method, Multi-analy-sis was carried out by COX regression. Results For these patients, the median survival time was 57. 2 months, the 5-year survival rate was 47. 9%. 25 patients received complete resection with 5-years survival rate 68%, 46 patients received partial resection with 5-years survival rate 36. 9%. 41 patients whose lump size was greater than or equal to 8 cm with 5-years survival rate 53. 6%, 40% with lower than 8 cm. Histology Masaoka staging with 5-years survival rate was stage II(57. 1%) , stage III(69. 7%) and stage IV(29. 0%) , respectively. Defferent his-tological type with 5-years survival rate squamous carcinoma(55. 1%) , adenocarcinoma (14. 3%) ,small cell car-cinoma ( 28. 6%) , adenosquamous carcinoma ( 33. 3%) , and carcinoid ( 100%) , respectively. The operation method, the maximum diameter, mass Masaoka stage and different pathology types for survival were statistically dif-ferent (P<0. 05). Preoperative treatment, postoperative radiotherapy and differentiation degree of survival had no statistical difference. Conclusion Surgical method, lump size, masaoka stage and histological type are the impor-tant factors affecting prognosis. Adjuvant radiotherapy maybe is not the poor prognosis factor of thymic tumors. Sur-gical method and lump size are the significant independent prognostic factors in patients with thymic tumors.
6.Characteristics of cisplatin resistance in human gastric cancer cell line SGC-7901
Nana HUANG ; Yiyin ZHANG ; Kangsheng GU
Acta Universitatis Medicinalis Anhui 2015;(3):298-301
Objective To investigate the characteristics of cisplatin resistance in human gastric cancer cell line SGC-7901 . Methods Single cell gel electrophoresis ( SCGE ) was used to measure the level of DNA damage and repair in gastric cancer cell line SGC-7901 and gastric cancer cisplatin resistance cell line SGC-7901/DDP by ob-serving the tail length. Morphological changes of SGC-7901 and SGC-7901/DDP were recorded to evalutate the differences between the two lines. The degree of migration of SGC-7901/DDP and SGC-7901 measured by cell wound scratch assay was used to estimate the ability of invasion. MTT assay was performed to determine the drug sensitivity, IC50 values and cross-resistance of SGC-7901/DDP treated with 5-FU, VP-16, ADM, TAX and LOHP separately. Results The level of DNA damage and repair in SGC-7901/DDP was higher than that in SGC-7901 ac-cording to the tail length of SCGE tests ,suggesting the relationship between cisplatin resistance and the abiity of DNA damage and repair. There was a much smaller volume in SGC-7901/DDP compared with SGC-7901,and clone aggregation always appeared in SGC-7901/DDP. Cell wound scratch assay showed that the migration of SGC-7901/DDP was weaker than that of SGC-7901. MTT showed the significant increase of IC50 and cross resitance in SGC-7901/DDP compared with SGC-7901 treated with 5-FU, VP-16, ADM, TAX and LOHP simultaneously. Conclu-sion The ability of DNA damage and repair in gastric cancer cisplatin resistance cell line SGC-7901 is enhanced significantly. The SGC-7901/DDP shows a notable promotion on multidrug resistance in vivo, and the migration of SGC-7901/DDP is weaker than that of SGC-7901 .
7.The relationship between CD10,Bcl-6,VEGF with the prognosis in the primary gastrointestinal diffuse large B-cell lymphoma
Acta Universitatis Medicinalis Anhui 2015;(6):829-832
Objective To investigate the correlation between the expression of CD10,Bcl-6,VEGF with clinical characteristics and the prognosis in the primary gastrointestinal diffuse large B-cell lymphoma. Methods The clini-cal characteristics data of 66 patients with PGI-DLBCL were determined the levels of CD10,Bcl-6 and VEGF by immunohisto-chemical staining. Analyzed their correlation via Kaplan-Meier method and Log-rand test. Results Among those 66 patients,there were 36 cases(54. 5% )of primary stomach,while other 30 cases(45. 5% )were primary intestinal. 39 cases were GCB and 27 cases were non-GCB. The tumor stage and IPI were inverse propor-tion with the prognosis. The median progression-free-survival of GCB was 21. 50 months while non-GCB was 12. 00 months. The positive expression rate of Bcl-6 was 43. 9%(29 / 66)while that of CD10 was 34. 8%(23 / 66)and there were 29 cases(43. 9% )with positive expression of VEGF. Log-rank test revealed there was a positive correc-tion between the positive impression of CD10,Bcl-6 and PFS. On the contrary,the relationship between the ex-pressions of VEGF and PFS was negative. The expressions of CD10,Bcl-6 and VEGF were not correlated with clini-cal features. Cox multivariable analysis showed that the curative effect,the expressions of Bcl-6 and VEGF were in-dependent prognostic factors. Conclusion PGI-DLBCL is a highly invasive and heterogeneous malignancy. The stage of disease,the Hans classification,the level of IPI,the expression of CD10,Bcl-6 and VEGF may play im-portant roles in predicting the curative effect and the prognosis of the disease.
8.Effect on spontaneous activity in mice peripherally infected with influenza A WSN33 virus
Yanlin ZHOU ; Rui LI ; Liming GU ; Jun LIU ; Yanxia CHEN ; Kangsheng LI ; Gefei WANG
Chinese Journal of Immunology 2015;(5):603-606
Objective:To study the rule of spontaneous behavior and to explore the effect on emotion of mice peripherally infected with influenza A WSN33 virus( H1N1).Methods: Mice were intranasal inoculated with H1N1 WSN33 or saline.Then mice bodyweight change,and total distance movement,average movement speed distance in the central area and feces in the open field test in 5 minutes were recorded in two weeks.Results: Mice following WSN33 infection bodyweight declined sharply until day 7 post-inoculation,and mice bodyweight recovered from influenza infection at day 8 post-inoculation.Total distance movement of mice following H1N1 WSN33 infection decreased in the open field test,and difference of the reduction was significant from day 5 to day 10 post-inocu-lation.The average movement speed had no statistical difference.The range of numbers of fecal grains was large, and they were no significant difference.Conclusion:The total distance movement decreased,but average movement speed did not change following mice infected with H1N1 WSN33.They told us that mice infected with H1N1 WSN33 had anxiety,depressed and nervous emotion which is more evident in acute stage and early recovery stage,whereas the change of the nervous emotion was small and not obvious.
9.Progress of chemotherapy drug sensitivity markers for gastric cancer
Journal of International Oncology 2013;(1):61-64
Fluorouracil,platinum and taxane are commonly used in the current chemotherapy of gastric cancer.The relationship between the key molecular biomarkers of mechanism of drug action and drug sensitivity has become a researchful hotspot,which is the prerequisite to achieve individualized treatment of gastric cancer.
10.Molecular markers for prognosis of gastric cancer
Journal of International Oncology 2013;(6):456-459
A variety of molecular markers are related to the prognosis of gastric cancer,such as the the loss expression of AT rich interactive domain 1A (ARID1A),the overexpression of CD133 and survivin are releated to the incidence and poor prognosis of gastric cancer; leptin,CD44 and microRNA (miRNA) are releated to the invasion and metastasis of gastric cancer; the low expression of secreted protein acidic and rich in cysteine (SPARC) contributes to the angiogenesis of gastric cancer,but the relationship between SPARC and prognosis needs further study; the expression and gene polymorphism of excision repair cross-complementing 1 (ERCC1) may be useful for choice of medication in the treatment of gastric cancer.


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