Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adju...Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.展开更多
Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:...Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.展开更多
Objective:Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma(PTCL).This phase 1 b study evaluated the safety,pharmacokinetics,and prelim...Objective:Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma(PTCL).This phase 1 b study evaluated the safety,pharmacokinetics,and preliminary efficacy of chidamide in combination with cyclophosphamide,doxorubicin,vincristine and prednisone(CHOP)for treatment-na?ve PTCL patients.Methods:This study was an open-label,multicenter trial composed of dose escalation and dose expansion.Patients received CHOP for six 21-d cycles and chidamide on d 1,4,8 and 11 in each cycle.Four dose levels of chidamide(20,25,30 and 35 mg)were evaluated.The primary objective was to evaluate the safety and tolerability of the combination regimen.Results:A total of 30 patients were evaluated in this study:15 in the dose-escalation part and 15 in the doseexpansion part.In the dose-escalation study,three patients were enrolled in the 35 mg chidamide cohort.One had dose-limiting toxicity with grade 3 vascular access complications,and one had grade 2 neutropenia with a sustained temperature>38°C.Dose escalation was stopped at this chidamide dose level.The most common(≥10%)grade 3 or 4 adverse events(AEs)were leukopenia(90.0%),neutropenia(83.3%),vomiting(13.3%),thrombocytopenia(10.0%)and febrile neutropenia(10.0%).No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment.The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3%(25/28),with 16(57.1%)achieving complete response or unconfirmed complete response.The estimated median progression-free survival was 14.0 months.In summary,we chose chidamide 30 mg as the recommended dose for phase 2.Conclusions:The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients,which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.展开更多
Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel a...Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.展开更多
Objective Due to the rarity of angioimmunoblastic T-cell lymphoma(AITL),very limited data concerning its incidence patterns and prognostic factors are available.This study aimed to explore the incidence,characteristic...Objective Due to the rarity of angioimmunoblastic T-cell lymphoma(AITL),very limited data concerning its incidence patterns and prognostic factors are available.This study aimed to explore the incidence,characteristics,survival outcomes,and prognostic factors of AITL.Methods Age-adjusted incidence and temporal trends were calculated based on 1247 AITL patients from the National Cancer Institute’s Surveillance,Epidemiology,and End Results(SEER)-13 database.A total of 1525 AITL patients from the SEER-18 database and 43 patients from our single center were included for survival analysis and nomogram construction.Results The age-adjusted incidence for overall cohort was 0.123[95%confidence interval(CI),0.117–0.131)per 100000 during 1992–2017.The overall incidence increased steeply at the rate of 15.3%(95%CI 11.0%–19.8%,P<0.001)per year during 1992–2004,but remained stable during 2004–2017(P=0.200).Similar incidence trends were observed in age,sex,and stage subgroups.The final nomograms consisted of four variables:age at diagnosis,sex,Ann Arbor stage,and primary site.The concordance index(C-index)of the nomogram for 5-year overall survival prediction was 0.717,0.690 and 0.820 in the training cohort,validation cohort-1 and cohort-2,respectively.Regarding the disease-specific survival(DSS),the nomogram also demonstrated a good discrimination level,with the C-index for predicting the probability of DSS at 5 years of 0.716,0.682 and 0.813 for the three cohorts,respectively.The calibration displayed good concordance between the nomogram-predicted and actual observed outcomes.Conclusion The age-adjusted incidence for AITL was low during 1992–2017.The incidence continuously increased during 1992–2004,but remained stable during 2004–2017.The nomograms as proposed may provide a favorable and accurate prognostic survival prediction in AITL.展开更多
Three-dimensional （3D） quantitative structure-activity relationship （QSAR） studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity again...Three-dimensional （3D） quantitative structure-activity relationship （QSAR） studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity against pancreas cancer Panc-I cells and colon cancer HT-29 cells. The established 3D-QSAR models from the comparative molecular field analysis （CoMFA） in training set showed not only significant statistical quality, but also satisfying predictive ability, with high correlation coefficient values （R12= 0.911, R22= 0.985） and cross-validation coefficient values （q2= 0.580, q22= 0.722）. Based on the CoMFA contour maps, some key structural factors responsible for anticancer activity of these series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new curcumin-related compounds with anticancer activity and predicting their activities prior to synthesis.展开更多
BACKGROUND The role of oxidative stress in the pathogenesis of colorectal carcinoma(CRC)has garnered considerable interest recently.Specific oxidative factors have been implicated in the pathogenesis of adenomatous po...BACKGROUND The role of oxidative stress in the pathogenesis of colorectal carcinoma(CRC)has garnered considerable interest recently.Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma.AIM To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma.METHODS A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study.They were allocated in three groups;those with sporadic colon adenocarcinoma(n=56,32.9%),those with colonic polyps(n=33,19.4%)and healthy controls(n=81,47.7%).All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A,25(OH)D3,E,C,B12,folic acid,glutathione,selenium(Se),zinc(Zn),free iron(Fe^(2+)),and malondialdehyde and results were compared between groups.RESULTS Serum levels of vitamins C,E,D,Se,Zn,vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group(P=0.002,P=0.009,P<0.001,P<0.001,P<0.001,P=0.020 and P<0.001,correspondingly).Increased levels of vitamin E(P=0.004),vitamin D(P<0.001),Se(P<0.001)and Zn(P<0.001)seem to bestow a protective effect on the development of CRC.For vitamin D(P<0.001)and Zn(P=0.036),this effect seems to extend to the development of colon polyps as well.On the other hand,elevated serum levels of malondialdehyde are associated with a higher risk of CRC(OR=2.09 compared to controls,P=0.004).Regarding colonic polyp development,increased concentrations of vitaminΑand Fe^(2+) are associated with a higher risk,whereas lower levels of malondialdehyde with a lower risk.CONCLUSION Increased oxidative stress may play an important role in the pathogenesis and progression of CRC.Antioxidants’presence may exert a protective effect in the very early stages of colon carcinogenesis.展开更多
Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Met...Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Methods: The 4-anilinoquinazolines compounds were prepared by hydrolyzed, ringed, halagenated, substituded in turn from 2-amino-5-nitrobenzylcarbonitril. The synthesized 4- anilinoquinazoline compounds has been rudimentarily screened by using A431 tumor cell line which overexpresses epidermal growth factor receptor as model adopted MTT method. Results: Five 6-nitro-4-halo-sbstituted anilinoquinazolines and five 6-amino-4-halo-substituted anilinoquinazolines have been obtained,and all of them had anticancer activity. The anticancer activity of 6-amino substituted inhibitors was higher than that of 6-nitro substituted inhibitors. However, the difference of anticancer activity between two series of quinazoline was much less than that of their inhibiting EGFR tyrosine kinase activity. Conclusion: The probable reason for 6-nitro-4-anilinoquinazolines having anticancer activity in vitro was that they had been partially transformed to 6-amino-4-anilinoquinazolines through endocellular cytochrome oxidation-reduction system.展开更多
Research into anticancer substances madefrom Chinese herbal drugs and their clinicalapplication is gaining international attention bythe medical profession of the more than 20analogues of camptothecine isolated from C...Research into anticancer substances madefrom Chinese herbal drugs and their clinicalapplication is gaining international attention bythe medical profession of the more than 20analogues of camptothecine isolated from Camp-totheca tree in China, most exhibited anticanceractivity. Among them, 10-hydroxycamptothe-cine has a wide anticancer spectrum and is lesstoxic. In suspension, it exhibits some therapeu-tic effects on primary hepatic cancer, gastriccarcinoma, cancer of the urinary bladder andleukemia.展开更多
Dear Researchers,Proceedings of Anticancer Research is an international peer-reviewed and open access journal,which is devoted to the rapid publication of high quality original articles,reviews,case reports,short comm...Dear Researchers,Proceedings of Anticancer Research is an international peer-reviewed and open access journal,which is devoted to the rapid publication of high quality original articles,reviews,case reports,short communication and letters on all aspects of experimental and clinical oncology.展开更多
Chemotherapy-induced nausea and vomiting(CINV)is common in patients receiving moderately or highly emetogenic chemotherapy and is caused by the activation of peripheral and central nervous system pathways,with the neu...Chemotherapy-induced nausea and vomiting(CINV)is common in patients receiving moderately or highly emetogenic chemotherapy and is caused by the activation of peripheral and central nervous system pathways,with the neurokinin-1 receptor playing a central role in delayed CINV.Neurokinin-1 receptor antagonists(NK1RAs)in combination with other antiemetic agents are recommended in international and Chinese guidelines for the prevention of acute and delayed CINV.Therefore,a summary of current data for NK1RAs would be of great clinical utility.This article summarizes the available clinical and real-world data on the use of NK1RAs in CINV prophylaxis,with a focus on evidence from China,where three NK1RAs,aprepitant,fosaprepitant and netupitant,are currently approved.NK1RAs have demonstrated efficacy and favorable safety in the prevention of acute and delayed CINV.Further research is required to determine the optimal use of these drugs and to identify strategies for CINV management in specific patient populations.展开更多
Parkinson’s disease(PD)is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra that leads to reduced dopamine levels and impaired motor function.Current treatmen...Parkinson’s disease(PD)is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra that leads to reduced dopamine levels and impaired motor function.Current treatments only provide temporary symptom relief without addressing the underlying neuronal loss.A promising new approach for treating PD is stem cell therapy,particularly induced pluripotent stem cells and human pluripotent stem cells.They have the ability to differentiate into various neural cells,offering potential for neuronal replacement and restoration of brain function.Induced pluripotent stem cells are derived from reprogramming adult cells and present advantages such as genetic compatibility and reduced immune rejection,overcoming ethical concerns associated with embryonic stem cells.Preclinical studies show promising results,demonstrating that stem cells can differentiate into dopaminergic neurons and improve motor function in animal models.These advancements pave the way for clinical trials and potential long-term solutions for patients with PD.This review highlighted the significance of stem cell therapy in neuroregeneration and addressed pre-clinical successes,challenges in long-term safety,and ethical considerations,with the hope of revolutionizing PD treatment and improving patient outcomes.展开更多
Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcou...Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.展开更多
AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting cir-culating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood sam...AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting cir-culating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P< 0.001) and preoperative serum levels of CEA (P=0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented signif icant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RTPCR assay can provide useful information concerning disease stage and overall survival of CRC patients.展开更多
Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from ...Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.展开更多
Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in Nationa...Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.展开更多
基金supported in part by Grants from National Science-Technology Support Plan Projects of China (2014BAI09B12)National Major Project for New Drug Innovation of China (2008ZX09312 and 2012ZX09303012)the Ministry of Education Doctor Foundation of China (20010023018, 20050023045, and 200800230019)
文摘Background: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone(CHOP) is an eicient treatment of non-Hodgkin's lymphoma(NHL). This study aimed to assess the eicacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab(R-CHOP) by examining the stem cell mobilization in NHL patients. Factors afecting the collection of CD34+ cells were also explored.Methods: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were inancially eligible received R-CHOP for autologous peripheral blood stem cell(APBSC) mobilization; the remaining 25 patients received CHOP.Results: The median CD34+ cell yield was 7.01 × 106 cells/kg body weight(range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ber of apheresis procedures per patient was 1(range 1–3). The≥2.0 APBS× 106 cells/kg body weight. The median numC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group(P response(CR) rate in = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the completeB cell lymphoma patients as compared with CHOP(P = 0.01). No signiicant diferences in toxicity or engraftment were observed between the two groups.Conclusion: The present study demonstrated that dose-adjusted CHOP chemotherapy efectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.
基金supported by grants from National Natural Science Foundation of China(Grant No.81672932,81874380 and 81730108)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(Grant No.LR18H160001)+7 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.LY15H160028 and LY13H130002)the Science and Technology Development Fund,Macao SAR(130/2017/A3,0099/2018/A3)Zhejiang Province Medical Science and Technology Project(Grant No.2017RC007)Key Project of Zhejiang Province Ministry of Science and Technology(Grant No.2015C03055)Talent Project of Zhejiang Association for Science and Technology(Grant No.2017YCGC002)Zhejiang Province Science and Technology Project of TCM(Grant No.2019ZZ016)Key Project of Hangzhou Ministry of Science and Technology(Grant No.20162013A07,20142013A63)Zhejiang Provincial Project for the Key Discipline of Traditional Chinese Medicine(Grant No.2017-XK-A09)。
文摘Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.
基金supported by the sponsor Shenzhen Chipscreen Biosciences Co.,LTD.by grants from the China National Major Project for New Drug Innovation(No.2017ZX09304015)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-001)。
文摘Objective:Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma(PTCL).This phase 1 b study evaluated the safety,pharmacokinetics,and preliminary efficacy of chidamide in combination with cyclophosphamide,doxorubicin,vincristine and prednisone(CHOP)for treatment-na?ve PTCL patients.Methods:This study was an open-label,multicenter trial composed of dose escalation and dose expansion.Patients received CHOP for six 21-d cycles and chidamide on d 1,4,8 and 11 in each cycle.Four dose levels of chidamide(20,25,30 and 35 mg)were evaluated.The primary objective was to evaluate the safety and tolerability of the combination regimen.Results:A total of 30 patients were evaluated in this study:15 in the dose-escalation part and 15 in the doseexpansion part.In the dose-escalation study,three patients were enrolled in the 35 mg chidamide cohort.One had dose-limiting toxicity with grade 3 vascular access complications,and one had grade 2 neutropenia with a sustained temperature>38°C.Dose escalation was stopped at this chidamide dose level.The most common(≥10%)grade 3 or 4 adverse events(AEs)were leukopenia(90.0%),neutropenia(83.3%),vomiting(13.3%),thrombocytopenia(10.0%)and febrile neutropenia(10.0%).No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment.The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3%(25/28),with 16(57.1%)achieving complete response or unconfirmed complete response.The estimated median progression-free survival was 14.0 months.In summary,we chose chidamide 30 mg as the recommended dose for phase 2.Conclusions:The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients,which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-014)and National Key R&D Program of China(No.2021YFC2500700).
文摘Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.
基金supported by the China National Major Project for New Drug Innovation(No.2017ZX09304015)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-001).
文摘Objective Due to the rarity of angioimmunoblastic T-cell lymphoma(AITL),very limited data concerning its incidence patterns and prognostic factors are available.This study aimed to explore the incidence,characteristics,survival outcomes,and prognostic factors of AITL.Methods Age-adjusted incidence and temporal trends were calculated based on 1247 AITL patients from the National Cancer Institute’s Surveillance,Epidemiology,and End Results(SEER)-13 database.A total of 1525 AITL patients from the SEER-18 database and 43 patients from our single center were included for survival analysis and nomogram construction.Results The age-adjusted incidence for overall cohort was 0.123[95%confidence interval(CI),0.117–0.131)per 100000 during 1992–2017.The overall incidence increased steeply at the rate of 15.3%(95%CI 11.0%–19.8%,P<0.001)per year during 1992–2004,but remained stable during 2004–2017(P=0.200).Similar incidence trends were observed in age,sex,and stage subgroups.The final nomograms consisted of four variables:age at diagnosis,sex,Ann Arbor stage,and primary site.The concordance index(C-index)of the nomogram for 5-year overall survival prediction was 0.717,0.690 and 0.820 in the training cohort,validation cohort-1 and cohort-2,respectively.Regarding the disease-specific survival(DSS),the nomogram also demonstrated a good discrimination level,with the C-index for predicting the probability of DSS at 5 years of 0.716,0.682 and 0.813 for the three cohorts,respectively.The calibration displayed good concordance between the nomogram-predicted and actual observed outcomes.Conclusion The age-adjusted incidence for AITL was low during 1992–2017.The incidence continuously increased during 1992–2004,but remained stable during 2004–2017.The nomograms as proposed may provide a favorable and accurate prognostic survival prediction in AITL.
基金Supported by the National Natural Science Foundation of China(21272043,8127452)Science and Technology Planning Project of Guangdong Province(2011B090400573,2012B091000170)Guangdong Natural Science Foundation(S2011010004967)
文摘Three-dimensional （3D） quantitative structure-activity relationship （QSAR） studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity against pancreas cancer Panc-I cells and colon cancer HT-29 cells. The established 3D-QSAR models from the comparative molecular field analysis （CoMFA） in training set showed not only significant statistical quality, but also satisfying predictive ability, with high correlation coefficient values （R12= 0.911, R22= 0.985） and cross-validation coefficient values （q2= 0.580, q22= 0.722）. Based on the CoMFA contour maps, some key structural factors responsible for anticancer activity of these series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new curcumin-related compounds with anticancer activity and predicting their activities prior to synthesis.
文摘BACKGROUND The role of oxidative stress in the pathogenesis of colorectal carcinoma(CRC)has garnered considerable interest recently.Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma.AIM To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma.METHODS A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study.They were allocated in three groups;those with sporadic colon adenocarcinoma(n=56,32.9%),those with colonic polyps(n=33,19.4%)and healthy controls(n=81,47.7%).All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A,25(OH)D3,E,C,B12,folic acid,glutathione,selenium(Se),zinc(Zn),free iron(Fe^(2+)),and malondialdehyde and results were compared between groups.RESULTS Serum levels of vitamins C,E,D,Se,Zn,vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group(P=0.002,P=0.009,P<0.001,P<0.001,P<0.001,P=0.020 and P<0.001,correspondingly).Increased levels of vitamin E(P=0.004),vitamin D(P<0.001),Se(P<0.001)and Zn(P<0.001)seem to bestow a protective effect on the development of CRC.For vitamin D(P<0.001)and Zn(P=0.036),this effect seems to extend to the development of colon polyps as well.On the other hand,elevated serum levels of malondialdehyde are associated with a higher risk of CRC(OR=2.09 compared to controls,P=0.004).Regarding colonic polyp development,increased concentrations of vitaminΑand Fe^(2+) are associated with a higher risk,whereas lower levels of malondialdehyde with a lower risk.CONCLUSION Increased oxidative stress may play an important role in the pathogenesis and progression of CRC.Antioxidants’presence may exert a protective effect in the very early stages of colon carcinogenesis.
文摘Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Methods: The 4-anilinoquinazolines compounds were prepared by hydrolyzed, ringed, halagenated, substituded in turn from 2-amino-5-nitrobenzylcarbonitril. The synthesized 4- anilinoquinazoline compounds has been rudimentarily screened by using A431 tumor cell line which overexpresses epidermal growth factor receptor as model adopted MTT method. Results: Five 6-nitro-4-halo-sbstituted anilinoquinazolines and five 6-amino-4-halo-substituted anilinoquinazolines have been obtained,and all of them had anticancer activity. The anticancer activity of 6-amino substituted inhibitors was higher than that of 6-nitro substituted inhibitors. However, the difference of anticancer activity between two series of quinazoline was much less than that of their inhibiting EGFR tyrosine kinase activity. Conclusion: The probable reason for 6-nitro-4-anilinoquinazolines having anticancer activity in vitro was that they had been partially transformed to 6-amino-4-anilinoquinazolines through endocellular cytochrome oxidation-reduction system.
文摘Research into anticancer substances madefrom Chinese herbal drugs and their clinicalapplication is gaining international attention bythe medical profession of the more than 20analogues of camptothecine isolated from Camp-totheca tree in China, most exhibited anticanceractivity. Among them, 10-hydroxycamptothe-cine has a wide anticancer spectrum and is lesstoxic. In suspension, it exhibits some therapeu-tic effects on primary hepatic cancer, gastriccarcinoma, cancer of the urinary bladder andleukemia.
文摘Dear Researchers,Proceedings of Anticancer Research is an international peer-reviewed and open access journal,which is devoted to the rapid publication of high quality original articles,reviews,case reports,short communication and letters on all aspects of experimental and clinical oncology.
基金provided technical help and editorial assistance for this manuscriptsupport for this manuscript was also provided by Dr.Sharon Gladwin(Rude Health Consulting Limited)and funded by MSD Chinafunded by MSD China.
文摘Chemotherapy-induced nausea and vomiting(CINV)is common in patients receiving moderately or highly emetogenic chemotherapy and is caused by the activation of peripheral and central nervous system pathways,with the neurokinin-1 receptor playing a central role in delayed CINV.Neurokinin-1 receptor antagonists(NK1RAs)in combination with other antiemetic agents are recommended in international and Chinese guidelines for the prevention of acute and delayed CINV.Therefore,a summary of current data for NK1RAs would be of great clinical utility.This article summarizes the available clinical and real-world data on the use of NK1RAs in CINV prophylaxis,with a focus on evidence from China,where three NK1RAs,aprepitant,fosaprepitant and netupitant,are currently approved.NK1RAs have demonstrated efficacy and favorable safety in the prevention of acute and delayed CINV.Further research is required to determine the optimal use of these drugs and to identify strategies for CINV management in specific patient populations.
文摘Parkinson’s disease(PD)is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra that leads to reduced dopamine levels and impaired motor function.Current treatments only provide temporary symptom relief without addressing the underlying neuronal loss.A promising new approach for treating PD is stem cell therapy,particularly induced pluripotent stem cells and human pluripotent stem cells.They have the ability to differentiate into various neural cells,offering potential for neuronal replacement and restoration of brain function.Induced pluripotent stem cells are derived from reprogramming adult cells and present advantages such as genetic compatibility and reduced immune rejection,overcoming ethical concerns associated with embryonic stem cells.Preclinical studies show promising results,demonstrating that stem cells can differentiate into dopaminergic neurons and improve motor function in animal models.These advancements pave the way for clinical trials and potential long-term solutions for patients with PD.This review highlighted the significance of stem cell therapy in neuroregeneration and addressed pre-clinical successes,challenges in long-term safety,and ethical considerations,with the hope of revolutionizing PD treatment and improving patient outcomes.
文摘Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.
基金Supported by The Ministry of Development of the Greek Government (GGET-AKMON)
文摘AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting cir-culating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P< 0.001) and preoperative serum levels of CEA (P=0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented signif icant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RTPCR assay can provide useful information concerning disease stage and overall survival of CRC patients.
基金supported in part by grants from the National Technologies ResearchDevelopment Program of China during the 9th Five-Year Plan Period (A20199610396-906-01-12)+1 种基金the Ying Dong Fok Foundation for Young College Teacher (B231996001)Chinese National Major Project for New Drug Innovation (2008ZX09312, 2012ZX09303012)
文摘Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.
基金funded by grants from the National Science and Technology Support Program (No. 2014BAI09B12)Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-001)
文摘Objective: To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma(DLBCL)patients in China according to the primary site.Methods: A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site.Results: In the 1,085 patients, 679(62.6%) cases were nodal DLBCL(N-DLBCL) and 406 cases(37.4%) were extranodal DLBCL(EN-DLBCL). The most common sites of N-DLBCL were lymphonodus(64.8%), Waldeyer's ring(19.7%), mediastinum(12.8%) and spleen(2.7%), while in EN-DLBCL, stomach(22.4%), intestine(16.0%),nose and sinuses(8.9%), testis(8.4%), skin(7.9%), thyroid(6.9%), central nervous system(CNS)(6.4%), breast(5.7%), bone(3.4%), and salivary gland(2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival(OS) rate and progression-free survival(PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9%(P=0.008), and the 5-year PFS were57.0% and 49.0%(P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate(83.6%) and PFS rate(76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach,breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%,respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%.Conclusions: In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.
