2.Current research analysis and prospects on sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy.
Wen-Jia CHEN ; Xia MAO ; Yan-Qiong ZHANG ; Na LIN
China Journal of Chinese Materia Medica 2019;44(23):5231-5239
The wide application of artemisinins in the treatment of multiple cancers reflects the advantages of traditional Chinese medicine used in this field. The existing basic and clinical studies have revealed that artesunate can effectively suppress the malignant progression of breast cancer,colon cancer,leukemia,melanoma,ovarian cancer,prostate cancer,kidney cancer and various tumors in central nervous system. The pharmacological mechanisms of artesunate against cancers are reflected in many aspects,such as inhibiting tumor cell proliferation,invasion and metastasis,inducing tumor cell apoptosis and autophagy,regulating cell signal transduction and inhibiting tumor angiogenesis. Meanwhile,growing experimental evidences have indicated that artesunate has been used for the sensitization of radiotherapy with X-ray,β-ray,γ-ray and~(60)Co γ-ray,as well as chemotherapy with cisplatin,carboplatin and doxorubicin.This review collected basic and clinical studies on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy published on PubMed and CNKI during April 2000 and February 2019,and summarized the clinical positioning and application of artesunate,with the aim to provide a more comprehensive explanation on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy,and offer the inspiration and ideas for the development of radiotherapy and chemotherapy sensitizers,as well as cancer resistance reversal agents.
Artesunate/therapeutic use*
;
Carboplatin/therapeutic use*
;
Cell Line, Tumor
;
Cell Proliferation
;
Cisplatin/therapeutic use*
;
Doxorubicin/therapeutic use*
;
Humans
;
Neoplasms/radiotherapy*
;
Radiation-Sensitizing Agents/therapeutic use*
3.Analysis of clinical factors for the efficacy of TPF in treating hypopharyngeal carcinoma.
Lianhe LI ; Fuxian TAN ; Wenhui YUE ; Hongmei WANG ; Hongmin WANG ; Hao XUE ; Zhenlei WEN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(19):1705-1707
OBJECTIVE:
To summarize the clinical effect of TPF regimen in the treatment of hypopharyngeal carcinoma and explore various clinical factors affecting treatment efficacy.
METHOD:
The clinical data of 20 cases with hypopharyngeal carcinoma, who received TPF treatment, were analyzed retrospectively. After two courses of chemotherapy, based on radiographic outcomes, next treatment plan was developed. To sum up the clinical information, including the clinical type, patterns of tumor growth, pathologic type, tumor stage, lymph node metastasis, age and so on. To analyze possible influencing factors affecting curative effect.
RESULT:
(1) After 20 cases with hypopharyngeal carcinoma received two courses of TPF treatment, the effect was evaluated. Objective response rate was 65%. (2) In patients with hypopharyngeal carcinoma, the efficacy of TPF therapy was significantly related to the clinical type, patterns of tumor growth and pathologic type; there was no statistical significance in tumor stage, lymph node metastasis and age.
CONCLUSION
According to the clinical type, patterns of tumor growth and pathologic type of hypopharyngeal carcinoma, resistance to chemotherapy in hypopharyngeal carcinoma can be assessed, which provides important basis for designing individualized treatment plan.
Antineoplastic Combined Chemotherapy Protocols
;
therapeutic use
;
Cisplatin
;
therapeutic use
;
Fluorouracil
;
therapeutic use
;
Humans
;
Hypopharyngeal Neoplasms
;
therapy
;
Lymphatic Metastasis
;
Retrospective Studies
;
Taxoids
;
therapeutic use
;
Treatment Outcome
4.Rituximab combined with second line regimens for treatment of seven relapsed and refractory Hodgkin lymphoma patients.
Huimin LIU ; Heng LI ; Wenjie XIONG ; Shuhua YI ; Dehui ZOU ; Lugui QIU
Chinese Journal of Hematology 2015;36(7):578-582
OBJECTIVETo investigate the efficacy and safety of Rituximab combined with second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.
METHODSSeven patients with relapsed and refractory Hodgkin lymphoma were treated with Rituximab combined with second line regimen. Among them, two patients were treated with R-GDP (E) [rituximab, gemcitabine, cisplatin, dexamethasone (etoposide)] regimen, another two patients with R-IGVP (rituximab, ifosfamide, gemcitabine, vinorelbine, prednisone)regimen, and the left three patients with R-BEACOPP (rituximab, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)regimen. The efficacy and safety were evaluated during and after chemotherapy.
RESULTSThere're three male and four female patients, whose median age was 21 years (range 12-36 years) old. One patient was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and the other six patients as classical HL (four nodular sclerosis HL, one lymphocyte-rich classical HL and one hmixed cellularity HL). The median cycles of salvage therapy were 4(1-4), and the median follow-up was 29 months (24-58 months). Among these 7 patients, the complete remission was observed in 4 patients, stable disease in 2 patients, but one patient died during salvage therapy. The two-year survival rates were 85.7% and the major toxic effects were bone marrow suppression.
CONCLUSIONThese results indicate that the Rituximab combined with second line regimen is an effective therapy for relapsed and refractory Hodgkin lymphoma.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Child ; Cisplatin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Dexamethasone ; therapeutic use ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Female ; Hodgkin Disease ; drug therapy ; Humans ; Male ; Neoplasm Recurrence, Local ; Prednisone ; therapeutic use ; Procarbazine ; therapeutic use ; Remission Induction ; Rituximab ; therapeutic use ; Salvage Therapy ; Vinblastine ; analogs & derivatives ; Vincristine ; therapeutic use ; Young Adult
5.Rituximab plus Autologous Hemotopoietic Stem Cell Transplantation for The Treatment of CD5 Positive Diffuse Large B Cell Lymphoma with Autoimmune Hemolytic Anemia.
Yi-Qun HUANG ; Rui-Ji ZHENG ; Rong-Juan WU ; Xu-Dong MA
Journal of Experimental Hematology 2016;24(3):722-726
OBJECTIVETo summarize the clinical features and therapy experience of a case of CD5 positive diffuse large B cell lymphoma (CD5+ DLBCL) with autoimmune hemolytic anemia (AIHA).
METHODSA 49-years old patient was investigated. The routine blood examination, bone marrow smear, Coombs test, serological test, chest CT, abdominal MR and immunochemistry etc were performed for this patient; and therapeutic effects of the chemotherapy regimen consisting of rituximab plus autologous hematopoietic stem cell transplantation (auto-HSCT) were observed.
RESULTSThe cervical lymphnode biopsy confirmed CD5+ DLBCL; the severe anemia, reticulocyte increase, Coombs test positive, and erythroid hyperplasia in bone marrow all suggested the occurence of autoimmune hemolytic anemia (AIHA). After plasma exchange, immune suppression using methylprednisolone, blood transfusion, one course of chemotherapy with "R-CHOP-E", the symptoms of AIHA in patient disappeared. After a continuous treatment for 3 courses of "R-CHOP-E", the bone marrow infiltration appeared, which was assessed as "PD", then the treatment was changed to the "R-ESHAP" for 4 courses, the patient was reassessed as "CR". The patient subsequently underwent auto-HSCT, followed up for 6 months, patientis still "CR".
CONCLUSIONThe status of the CD5+ DLBCL patient with AIHA is severe, and the prognosis is poor. The curative effect of the chemotherapy regimen with rituximab plus auto-HSCT for this patien is well.
Anemia, Hemolytic, Autoimmune ; therapy ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD5 Antigens ; metabolism ; Cisplatin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Cytarabine ; therapeutic use ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; therapy ; Methylprednisolone ; therapeutic use ; Middle Aged ; Prednisone ; therapeutic use ; Rituximab ; therapeutic use ; Sentinel Lymph Node Biopsy ; Vincristine ; therapeutic use
6.A new vomiting animal model--mink.
Wang YUE ; Fang ZHANG ; Lei WANG ; Xuan FANG ; Yan-xia LIU ; Masaru MINAMI
Acta Pharmaceutica Sinica 2003;38(2):89-91
AIMTo establish a new, reliable vomiting model in minks.
METHODSAdult male minks (Mustela vison) were randomly divided into groups (n = 6). Cisplatin, apomorphine, copper sulfate and X-radiation were used to establish vomiting model. Retching and vomiting were observed after the vomiting models were given anti-vomiting agents. After the behavioral experiment, assay of 5-HT in the ileum was performed by immunohistologic method.
RESULTSCisplatin 7.5 mg.kg-1 i.p., apomorphine 1.6 mg.kg-1 s.c. and copper sulfate 40 mg.kg-1 ig were shown to evoke vomiting. Retching and vomiting were significantly inhibited in ondansetron and metoclopramide pretreated minks (P < 0.05, P < 0.01).
CONCLUSIONAs a new vomiting model, minks may be of great value in studying vomiting mechanism and screening new antiemetic drugs.
Animals ; Antiemetics ; therapeutic use ; Apomorphine ; Cisplatin ; Copper Sulfate ; Disease Models, Animal ; Male ; Metoclopramide ; therapeutic use ; Mink ; Ondansetron ; therapeutic use ; Vomiting ; chemically induced ; drug therapy
7.Enhancement effect of caffeine on chemotherapy of osteosarcoma in Fischer 344/N rats.
Jian CHEN ; Chuan-long GU ; Shuang-lin WAN ; Shun-wu FAN
Journal of Zhejiang University. Medical sciences 2005;34(5):390-394
OBJECTIVETo determine the enhancement effects of caffeine on chemotherapy of transplanted osteosarcoma in Fischer 344/N rats.
METHODSOsteosarcoma-bearing Fischer 344/N rats were treated with cisplatin 2.5 mg/kg (Group DDP), caffeine 90 mg/kg x 2 d (Group caffeine), and cisplatin 2.5 mg/kg plus caffeine 90 mg/kg x 2 d (Group DDP+caffeine), and the control group was treated with normal saline in the same volume. All drugs were given by intra-peritoneum injection with micro-pump, in the rate of 0.5 ml/h. The tumor volume was measured and evaluated. The tumors were stained in TUNEL, and PCNA was detected with immunohistochemistry. The tumor growth inhibition rate, PCNA index and apoptosis index were calculated, and the survival time were recorded.
RESULTSThe tumor inhibition rate was -0.5219 +/-0.1429 in control group, 0.0362 +/-0.0957 in Group DDP, -0.4193 +/-0.1345 in Group caffeine, and 0.3646 +/-0.1313 in Group DDP+caffeine (P <0.01). PCNA index was 0.4587 +/-0.1312 in control group, 0.1847+/-0.0535 in Group DDP, 0.4381 +/-0.0706 in Group caffeine, and 0.0314 +/-0.0231 in Group DDP+caffeine (P <0.01). Apoptosis index was 0.0008 +/-0.0005 in control group, 0.0077 +/-0.0060 in Group DDP, 0.0011 +/-0.0003 in Group caffeine, and 0.0295 +/-0.0069 in Group DDP+caffeine (P <0.01). And the survival time was (33.63 +/-4.63)d in control group, (52.13 +/-11.74)d in Group DDP, (35.63 +/-5.15)d in Group caffeine, and (55.13 +/-16.23)d in Group DDP+caffeine (P <0.01).
CONCLUSIONCaffeine could enhance the anti-tumor effect of cisplatin in rat osteosarcoma.
Animals ; Antineoplastic Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; pathology ; Caffeine ; therapeutic use ; Cisplatin ; therapeutic use ; Drug Synergism ; Neoplasm Transplantation ; Osteosarcoma ; drug therapy ; pathology ; Rats ; Rats, Inbred F344
8.Effects of radical radiotherapy combined with different regimens of chemotherapy on radiation intestinal injury in patients with non-metastatic anal squamous cell carcinoma.
Xiao Lin PANG ; Shuai LIU ; Yan Ping LIU ; Hai Yang CHEN ; Fang HE ; Jian ZHENG ; Xiang Bo WAN
Chinese Journal of Gastrointestinal Surgery 2021;24(11):977-983
Objective: To investigate the effects of radical radiotherapy combined with different chemotherapy regimens (fluorouracil-based versus docetaxel plus cisplatin) on the incidence of radiation intestinal injury and the prognosis in patients with non-metastatic anal squamous cell carcinoma. Methods: A retrospective cohort study was conducted to recruit non-metastatic anal squamous cell carcinoma patients who underwent chemoradiotherapy in the Sixth Affiliated Hospital of Sun Yat-sen University and Nanfang Hospital from July 2013 to January 2021. Inclusion criteria: (1) newly diagnosed anal and perianal squamous cell carcinoma; (2) completed radical radiotherapy combined with concurrent chemotherapy; (3) tumor could be evaluated before radiotherapy. Exclusion criteria: (1) no imaging evaluation before treatment, or the tumor stage could not be determined; (2) patients undergoing local or radical resection before radiotherapy; (3) distant metastasis occurred before or during treatment; (4) recurrent anal squamous cell carcinoma. A total of 55 patients (48 from the Sixth Affiliated Hospital of Sun Yat-sen University and 7 from Nanfang Hospital) were given fluorouracil (the 5-FU group, n=34) or docetaxel combined with the cisplatin (the TP group, n=21). The evaluation of radiation intestinal injury, hematological toxicity and 3-year disease-free survival (DFS) rate were compared between the two groups. The effects of chemotherapy regimen and other clinicopathological factors on the incidence and severity of acute and chronic radiation intestinal injury were analyzed. The assessment of radiation intestinal injury was based on the American Cancer Radiotherapy Cooperation Group (RTOG) criteria. Results: During radiotherapy and within 3 months after radiotherapy, a total of 45 patients developed acute radiation intestinal injury, including 18 cases of grade 1 (32.7%), 22 cases of grade 2 (40.0%) and 5 cases of grade 3 (9.1%). No patient developed chronic radiation intestinal injury. Among the 34 patients in the 5-FU group, 21 had grade 2-3 radiation intestinal injury (21/34, 61.8%), which was significantly higher than that in the TP group (6/21, 28.6%) (χ(2)=5.723, P=0.017). Multivariate analysis showed that 5-FU chemotherapy regimen was an independent risk factor for radiation intestinal injury (HR=4.038, 95% CI: 1.250-13.045, P=0.020). With a median follow-up period of 26 (5-94) months, the 3-year DFS rate of patients in TP group and 5-FU group was 66.8% and 77.9%, respectively, whose difference was not significant (P=0.478). Univariate analysis showed that the DFS rate was associated with sex, age, tumor location, T stage, N stage, and induction chemotherapy (all P<0.05), while the DFS rate was not associated with chemotherapy regimen or radiation intestinal injury (both P>0.05). Multivariate analysis revealed that age ≥ 50 years old was an independent risk factor affecting the prognosis of patients (HR=8.301, 95% CI: 1.130-60.996, P=0.038). Conclusions: For patients with non-metastatic anal squamous cell carcinoma, radical radiotherapy combined with TP chemotherapy regimen can significantly reduce the incidence of radiation intestinal injury as compared to 5-FU regimen. However, due to the short follow-up time, the effect of different chemotherapy regimens on the prognosis is not yet clear.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Anus Neoplasms/radiotherapy*
;
Carcinoma, Squamous Cell/radiotherapy*
;
Chemoradiotherapy
;
Cisplatin/therapeutic use*
;
Fluorouracil/therapeutic use*
;
Humans
;
Middle Aged
;
Neoplasm Recurrence, Local
;
Retrospective Studies
9.Research progress of copper transporter 1 in platinum-based chemotherapy.
Qianying OUYANG ; Yujie LIU ; Yingzi LIU
Journal of Central South University(Medical Sciences) 2018;43(12):1376-1379
Platinum drugs are widely used in the treatment of various solid tumors, but their resistance to platinum is the most significant obstacle to successful treatment. Copper transporter 1 (CTR1) is the specific transporter for copper, and it mainly locates at the plasma membrane and plays a role in pumping copper into the cell. CTR1 is also the major platinum influx transporter and plays a key role in platinum resistance. The expression, polymorphism, and degradation of CTR1 affect platinum resistance in tumors. Therefore, CTR1 may be a potential predictive biomarker of platinum resistance and a therapeutic target for overcoming platinum resistance.
Antineoplastic Agents
;
therapeutic use
;
Cation Transport Proteins
;
genetics
;
metabolism
;
Cisplatin
;
therapeutic use
;
Copper
;
Copper Transporter 1
;
Drug Resistance, Neoplasm
;
genetics
;
Platinum
;
therapeutic use
;
Research
;
trends
10.Study of the clinical significance of ETAR mRNA expression in high-grade serous ovarian cancer and the inhibitory effect of ETAR derived fusion polypeptide on cancer progression.
Yan Ling ZHANG ; Xiao Kun XIA ; Meng ZHANG
Chinese Journal of Obstetrics and Gynecology 2023;58(12):930-938
Objective: To investigate the clinical significance of endothelin A receptor (ETAR) expression in high-grade serous ovarian carcinoma (HGSOC). To design ETAR carboxyl terminal (ETAR-C) amino acids derived polypeptide and to study the inhibitory effect on ovarian epithelial carcinoma cells in vitro. Methods: (1) A total of 126 patients who received surgical treatment and were diagnosed with HGSOC by postoperative pathological examination in Central Hospital of Xuzhou from January 1, 2007 to December 31, 2017 were selected. All patients had completed clinicopathological data and follow-up data. Cancer tissue samples were collected and ETAR mRNA expression in HGSOC tissues was detected by reverse transcript-PCR. The clinical significance was analyzed. (2) ETAR-C fusion polypeptide was designed based on the sequence of carboxyl terminal amino acids of ETAR, expressed and purified in vitro. The effects of ETAR-C fusion polypeptide on migration and invasion ability of ovarian cancer SKOV3 and CAOV3 cells were detected by scratch test and invasion test, respectively. The effect of ETAR-C fusion polypeptide on chemosensitivity of cisplatin-resistant ovarian cancer SKOV3/cDDP and CAOV3/cDDP cells was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The effect of ETAR-C fusion polypeptide on β-arrestin-1 expression in ovarian cancer SKOV3 and CAOV3 cells was detected by western blot. Results: (1) The relative expression level of ETAR mRNA in HGSOC tissues was 18.6±5.1. Patients with HGSOC were divided into high ETAR mRNA expression (n=76) and low ETAR mRNA expression (n=50) with 61.7% as cut-off value analyzed by X-Tile software. High expression of ETAR mRNA was significantly correlated with abdominal water volume, platinum drug resistance, and cancer antigen 125 (CA125) value in HGSOC patients (all P<0.05), but was not related to the age of patients with HGSOC and the size of postoperative residual lesions (all P>0.05). The 5-year progression free survival rates were 18.4% and 28.0%, and the 5-year overall survival rates were 38.2% and 52.0% in HGSOC patients with high and low ETAR mRNA expression respectively, there were statistically significant differences (P=0.046, P=0.034). (2) The results of scratch test and invasion test showed that the scratch healing rate and cell invasion rate of SKOV3 or CAOV3 cells treated with endothelin-1 (ET-1) and ET-1+ETAR-C were respectively compared, and the differences were statistically significant (all P<0.05). MTT assay showed that the inhibition rates of ETAR-C fusion polypeptide treated in SKOV3/cDDP and CAOV3/cDDP cells were significantly higher than those of control cells after the addition of 4, 6, 8, 10, 12, and 24 μg/ml cisplatin (all P<0.05). Western blot analysis showed that the relative expression levels of β-arrestin-1 in SKOV3 or CAOV3 cells treated with ET-1 and ET-1+ETAR-C were 1.85±0.09 and 1.13±0.09 (SKOV3 cells), 2.14±0.15 and 1.66±0.12 (CAOV3 cells), respectively. The differences were statistically significant (all P<0.05). Conclusions: The prognosis of HGSOC patients with high expression of ETAR mRNA is significantly worse than those with low expression of ETAR mRNA. ETAR might be a new target for HGSOC treatment. The ETAR-C fusion polypeptide that interferes with the interaction of ETAR and β-arrestin-1 has good inhibitory effect on ovarian cancer cells in vitro, and might have clinical application potential.
Female
;
Humans
;
Amino Acids/therapeutic use*
;
beta-Arrestins/therapeutic use*
;
Cell Line, Tumor
;
Cisplatin/pharmacology*
;
Clinical Relevance
;
Ovarian Neoplasms/pathology*
;
Receptor, Endothelin A/therapeutic use*
;
RNA, Messenger/metabolism*