As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer of...As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.展开更多
Mucosal melanoma(MM)is extremely rare in Caucasians,whereas it is the second predominant melanoma subtype in Asian and other non-Caucasian populations.Distinct from cutaneous melanoma in terms of epidemiology,biology,...Mucosal melanoma(MM)is extremely rare in Caucasians,whereas it is the second predominant melanoma subtype in Asian and other non-Caucasian populations.Distinct from cutaneous melanoma in terms of epidemiology,biology,and molecular characteristics,MM is characterized by more aggressive biological behavior,lower mutational burden,more chromosomal structure variants,and poorer prognosis.Because of the rarity of MM,its biological features are not fully understood,and potential novel therapies are less well depicted.Whereas immunotherapy has shown encouraging efficacy for cutaneous melanoma,its efficacy in MM is unclear due to limited sample sizes in clinical trials.Thus,in this review,we describe the epidemiological,clinical,and molecular features of MM and summarize the efficacies of different immunotherapies for MM,including immune checkpoint inhibitors,vaccines,oncolytic virus therapy,adoptive T-cell therapy,and various combination therapies.展开更多
BACKGROUND Antiangiogenic agents(AAs)are increasingly used to treat malignant tumors and have been associated with gastrointestinal(GI)bleeding and perforation.Elective surgeries and endoscopy are recommended to be de...BACKGROUND Antiangiogenic agents(AAs)are increasingly used to treat malignant tumors and have been associated with gastrointestinal(GI)bleeding and perforation.Elective surgeries and endoscopy are recommended to be delayed for 31 d until after AAs treatment.Data regarding the safety of endoscopy while on antiangiogenic agents is extremely limited.No guidelines are in place to address the concern about withholding these anti-angiogenic drugs.AIM To evaluate the risks of endoscopy in patients on antiangiogenic agents from 2015 to 2020 at our institution.METHODS This is a single centered retrospective study approved by the institutional review board statement of the institution.Patients that underwent endoscopy within 28 d of antiangiogenic agents’treatment were included in the study.Primary outcome of interest was death,and secondary outcomes included perforation and GI bleeding.Data were analyzed utilizing descriptive statistics.Fifty-nine patients were included in the final analysis and a total of eighty-five procedures were performed that were characterized as low risk and high risk.RESULTS Among the 59 patients a total of 85 endoscopic procedures were performed with 24(28.2%)categorized as high-risk and 61(71.8%)procedures as low-risk.Of the total number of patients,(50%)were on bevacizumab and the rest were on imatinib(11.7%),lenvatinib(6.7%)and,ramucirumab(5%).The average duration between administration of AAs and the performance of endoscopic procedures was 9.9 d.No procedure-related adverse events were noted among our study population.We did observe two deaths with one patient,on lenvatinib for metastatic hepatocellular carcinoma,who had persistent bleeding despite esophageal variceal banding and died 4 d later from hemorrhagic shock.Another patient was diagnosed with acute myeloid leukemia died 24 d after an esophagogastroduodenoscopy with biopsy after transition to comfort care.CONCLUSION As per this single center retrospective study,the rate of endoscopic procedure-related adverse events and death within 28 d of AA administration appears to be low.展开更多
Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequ...Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension(PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The Pub Med database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: "liver cirrhosis", "portal hypertension", "pathogenesis", "angiogenesis", and "antiangiogenic therapy". Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studie donly in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.展开更多
● AIM: To evaluate the clinical efficacy and safety of ranibizumab for wet age-related macular degeneration(w AMD) in Chinese patients and to determine the mean number of injections administered over one year of foll...● AIM: To evaluate the clinical efficacy and safety of ranibizumab for wet age-related macular degeneration(w AMD) in Chinese patients and to determine the mean number of injections administered over one year of follow-up. ● METHODS: This single centre, retrospective observational case series study included data from 121 patients with w AMD(121 eyes) who were diagnosed by indirect ophthalmoscopy, fluorescence fundus angiography(FFA), indocyanine green angiography, and optical coherence tomography. Ranibizumab was injected into the vitreous cavities once per month for 3 mo and as needed afterwards. Changes in visual acuity and central foveal thickness(CFT) during the follow-up period were compared, and the mean number of injections over the year was calculated. Patients with one or more adverse events related to the drugs and injections were recorded for further adverse events analysis. ● RESULTS: The study population included 70 males and 51 females aged between 50 and 87y(mean: 71.32±9.41y). The mean number of injections over the first year was 5±1(range: 3-9). The mean best-corrected visual acuity by Early Treatment Diabetic Retinopathy Study increased from 43.2±19.3(95%CI: 39.8-46.7) at baseline to 51.7±20.1(95%CI: 48.1-55.3), and CFT decreased from 526.5±277.0 μm(95%CI: 476.6-576.4) to 258.2±161.6 μm(95%CI: 229.2-287.3) at 12 mo. The differences were statistically significant(P<0.001). Visual acuity significantly improved in 34.1% of the patients(38 eyes), stabilized in 66.1% of the patients(80 eyes), and significantly decreased in 2.5% of the patients(3 eyes). CFT at baseline was an independent risk factor of decreased CFT and increased visual acuity. None of the patients had severe adverse events during the follow-up period.● CONCLUSION: Ranibizumab can effectively control disease progression and improve visual acuity in patients with w AMD. The disease conditions of most patients stabilized after a one-year treatment with an average of 5 injections.展开更多
BACKGROUND Although hepatocellular carcinoma(HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected results.AIM To uncover immunohistochemical(IHC) aspects of angiogenesis i...BACKGROUND Although hepatocellular carcinoma(HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected results.AIM To uncover immunohistochemical(IHC) aspects of angiogenesis in HCC.METHODS A retrospective cohort study was performed and 50 cases of HCC were randomly selected. The angiogenesis particularities were evaluated based on the IHC markers Cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) A and the endothelial area(EA) was counted using the antibodies CD31 and CD105.RESULTS The angiogenic phenotype evaluated with VEGF-A was more expressed in small tumors without vascular invasion(pT1), whereas COX-2 was rather expressed in dedifferentiated tumors developed in non-cirrhotic liver. The CD31-related EA value decreased in parallel with increasing COX-2 intensity but was higher in HCC cases developed in patients with cirrhosis. The CD105-related EA was higher in tumors developed in patients without associated hepatitis.CONCLUSION In patients with HCC developed in cirrhosis, the newly formed vessels are rather immature and their genesis is mediated via VEGF. In patients with non-cirrhotic liver, COX-2 intensity and number of mature neoformed vessels increases in parallel with HCC dedifferentiation.展开更多
Objective:Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans（M.fragrans）（nutmeg） and Morinda citrifolia（M.citrifolia）（mengkudu） oils. Methods:The nutmeg and megkudu ess...Objective:Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans（M.fragrans）（nutmeg） and Morinda citrifolia（M.citrifolia）（mengkudu） oils. Methods:The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essenlial oils were delermined by beta-carotene/ linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations.Results:The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil.The nutmeg oil effectively inhibited the oxidation of linoleic acid with（88.68±0.1）%while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is（69.44±0.4）%.The nutmeg oil and mengkudu oil showed reducing power with an EC<sub>50</sub> value of 181.4μg/mL and 3 043.0μg/mL,respectively.The anliangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC<sub>50</sub> of 77.64μg/mL comparing to mengkudu oil which exhibits IC<sub>50</sub> of 109.30μg/mL.Conclusion:Bioactive compound（s） will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs.展开更多
Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential coll...Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential collaborations among researchers all over the world.In this article,10 more questions are presented as followed.Question 57.What are the major stresses that drive the formation,progression,and metastasis of a cancer? Question 58.What is the mechanism responsible for altering an acidic intracellular pH and a basic extracellular pH in normal tissue cells to a basic intracellular pH and an acidic extracellular pH in cancer cells,a fundamental and yet largely ignored phenomenon? Question 59.Where are the tumor-associated plasma microRNAs from in cancer patients? Question 60.Can we identify mechanisms employed by tumor subpopulations to evade standard therapies and seed relapse/metastatic tumors before treatment? Question 61.Why are mutation rates in epidermal growth factor receptor(EGFR) and erb-b2 receptor tyrosine kinase 2(ERBB2) higher in lung cancer from never smokers than that from smokers? Question 62.Does tumor vasculogenic mimicry contribute to the resistance against antiangiogenic therapy in renal cancer? Question 63.What molecular targeted drugs would be effective for non-clear cell renal cell carcinoma(RCC),especially metastatic papillary RCC and chromophobe RCC? Question 64.Can it be more effective by targeting both the vascular endothelial growth factor receptor(VEGFR) and MET signaling pathways in sporadic metastatic papillary renal cell carcinoma(RCC)? Question 65.What are the predictive biomarkers that may be used to identify the renal cell carcinoma(RCC) patients who can benefit from immune checkpoint inhibitor treatment? Question 66.How do we identify predictive molecular biomarkers to stratify clear cell renal cell carcinoma patients for targeted therapies?展开更多
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, ...Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77.How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?展开更多
Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and...Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and the absolute stereochemistry of 1 was determined by single crystal X-ray experiment.Compound 4 showed antiangiogenic activity evaluated by a zebrafish model and apoptosis-inducing effect on A549 lung cancer cells.展开更多
Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarel...Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarelix,a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer,may have antiangiogenic effects via its capacity to block follicle stimulating hormone(FSH)production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens.The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment.Degarelix induced a rapid decrease in FSH level.This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year.Contrast-enhanced ultrasonography demonstrated reduction of tumor vas-clature.This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug.展开更多
Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged par...Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi-zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.展开更多
Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic...Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).展开更多
Background:Endostatin(ES) is a well-established potent endogenous antiangiogenic factor.An ES variant,called zinc-binding protein-ES(ZBP-ES),is clinically available;however,its use is limited by rapid renal clearance ...Background:Endostatin(ES) is a well-established potent endogenous antiangiogenic factor.An ES variant,called zinc-binding protein-ES(ZBP-ES),is clinically available;however,its use is limited by rapid renal clearance and short residence time.PEGylation has been exploited to overcome these shortcomings,and mono-PEGylated ES(called M_2ES) as well as mono-PEGylated ZBP-ES(MZBP-ES) are developed in our study.This study aimed to compare the biophysical properties and biological effects of M_2ES and MZBP-ES to evaluate their druggability.Methods:Circular dichroism and tryptophan emission fluorescence were used to monitor the conformational changes of M_2ES and MZBP-ES.Their resistance to trypsin digestion and guanidinium chloride(GdmCl)-induced unfolding was examined by Coomassie staining and tryptophan emission fluorescence,respectively.The biological effects of M_2ES and MZBP-ES on endothelial cell migration were evaluated using Transwell migration and wound healing assays,and the uptake of M_2ES and MZBP-ES in endothelial cells was also compared by Western blotting and immunofluorescence.Results:Structural analyses revealed that M_2ES has a more compact tertiary structure than MZBP-ES.Moreover,M_2ES was more resistant to trypsin digestion and GdmCI-induced unfolding compared with MZBP-ES.In addition,although M_2ES and MZBP-ES showed comparable levels of inhibiting transwell migration and wound healing of endothelial cells,M_2ES displayed an increased ability to enter cells compared with MZBP-ES,possibly caused by the enhanced interaction with nucleolin.Conclusions:M_2ES has a more compact tertiary structure,is more stable for trypsin digestion and GdmCI-induced unfolding,exhibits increased cellular uptake and shows equivalent inhibitory effects on cell migration relative to MZBP-ES,indicating that M_2ES is a more promising candidate for anticancer drug development compared with MZBP-ES.展开更多
BACKGROUND Squamous cell carcinoma (SCC) is one the most common subtypes of non-small cell lung cancer, yet the treatment options for it remain limited. Here, we report a case of advanced SCC and review the related li...BACKGROUND Squamous cell carcinoma (SCC) is one the most common subtypes of non-small cell lung cancer, yet the treatment options for it remain limited. Here, we report a case of advanced SCC and review the related literature focusing on the multiline therapy method. CASE SUMMARY We report the case of a 45-year-old man with advanced SCC who was deemed inoperable at the time of advanced SCC diagnosis. The patient had been referred to our hospital in April 2013 with complaints of a stuffy feeling in the chest, dyspnea, and pain in the right shoulder lasting for 1 mo. Physical examination found no obvious abnormalities, except for lower breath sound in the right lower lung. Laboratory data were within normal limits. Immunohistochemistry analysis of the tumor tissue showed CK5/6 (+), p63 (+), CD56 (+), and Ki-67 (+, approximately 30%), and genetic testing detected no EGFR mutation. He received a multiline treatment that included chemotherapy, radiotherapy, targeted therapy, and antiangiogenic therapy. After more than 5-year comprehensive treatment, the patient remains alive. CONCLUSION This typical case highlights the importance of appropriate multiline therapy for those patients with advanced SCC.展开更多
Metastatic renal cell cancer(mRCC)management has undergone a paradigm shift in recent decades.The first revolution came with the emergence of vascular endothelial growth factor inhibitors;there was a second wave with ...Metastatic renal cell cancer(mRCC)management has undergone a paradigm shift in recent decades.The first revolution came with the emergence of vascular endothelial growth factor inhibitors;there was a second wave with the unprecedented success of checkpoint inhibitors,and then the latest approach,which is becoming the new care standard in mRCC,of combining these two strategies in different ways.Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival(PFS),overall survival(OS),and objective response rate(ORR)in intermediate and high-risk patients.However,several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place,and so far,the only one for nivolumab/ipilimumab is the frontline setting.The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembrolizumab/axitinib over sunitinib in favorable-risk mRCC,suggesting that it should no longer be the first line of choice in low-risk patients.Finally,the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS,OS,and ORR,providing a new first-line option among all International Metastatic RCC Database Consortium risk patients.Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib,cabozantinib/atezolizumab,and lenvatinib/pembrolizumab,providing promising grounds upon which to start phase III studies.In addition,other works are using novel therapeutic agents with different mechanisms of action,including telaglenastat(a glutaminase inhibitor),entinostat[an inhibitor of histone deacetylases(HDACs)],and olaparib and talazoparib,poly(ADP-ribose)polymerase inhibitors widely used in other tumors.However,some questions regarding mRCC management still need to be addressed,such as head-to-head comparisons between the current options,treatment sequencing,non-clear cell mRCC,and the role of biomarkers to ascertain the best treatment choice.展开更多
BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tu...BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.展开更多
Endometriosis is an inflammatory oestrogen dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The modern advance in treatment of endometriosis management is tackling the ...Endometriosis is an inflammatory oestrogen dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The modern advance in treatment of endometriosis management is tackling the debilitating pain it causes, besides the infertility in patients desiring fertility in reproductive age group. This can be achieved by surgical or medical means, although in most cases a combination of both treatments is required. Usually, long term treatment is required in most cases. Unfortunately in most cases, pain symptoms recur between 6months and 12 months once treatment is stopped. A lot of research has gone in understanding the pathogenesis and further medical management of endometriosis besides surgery to be useful in relieving pain and use in patients desiring fertility besides hormonal treatments used earlier like hormonal contraceptives (oral, transdermal or vaginal administration), progestogens, danazol, Gonadotrophic releasing hormone agonist (GnRH), aromatase inhibitors. Newer agents like antiangiogenic drugs, phytochemical agents like resveratrol, TNF-α inhibitors, GnRH antagonists like egalogolix, statins, antiinflammatory agents like COX2 Inhibitors and PPARγ inhibitors like pioglitazone etc., with recent work of combined efficacy of telmesartan of both PPARγ partial agonism along with angiotensin 1 receptor agonism having more efficacy, role of immunomodulators like rapamycin, lipoxin 4 and pentoxyphylline, GnRH antagonists like egalogolix are still under study undergoing phase III trials although preliminary results show promising results with fewer side effects as compared to similar duration of GnRH agonist and much less BMD side effects. Increasing number of trials show the safety of SPRM’s, along with efficacy although disadvantage is suppression of fertility so cannot be used for women desiring fertility. Currently, only mifepristone and ulipristal have received FDA approval for indication in fibroid treatment, MTP and not for endometriosis as yet. The advantages and disadvantages of all the recent advances are discussed in an update in the pathophysiology as well medical treatment of endometriosis.展开更多
AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separat...AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126and thalidomide for solid tumors.展开更多
BACKGROUND Thymic-enteric adenocarcinoma with positive expression of CDX2 and CK20 is rare in adults,with only 16 reported cases.However,standard treatment options for this type of thymic adenocarcinoma has not yet be...BACKGROUND Thymic-enteric adenocarcinoma with positive expression of CDX2 and CK20 is rare in adults,with only 16 reported cases.However,standard treatment options for this type of thymic adenocarcinoma has not yet been established.Therefore,we report a case of stage IV thymic-enteric adenocarcinoma treated with radiotherapy,chemotherapy,and anti-angiogenesis therapy.CASE SUMMARY We report a case of thymic-enteric adenocarcinoma occurring in a 44-year-old woman.The tumor was considered unresectable owing to its invasiveness.The patient was treated with six cycles of oxaliplatin(130 mg/m^(2),day 1)and capecitabine(1000 mg/m^(2) BID,days 1-14).During the first three cycles of chemotherapy,concurrent radiotherapy(60 Gy/30 fractions)and anti-angiogenic therapy using apatinib were recommended.The primary tumor achieved partial remission based on the Response Evaluation Criteria in Solid Tumors.During follow-up,there was no evidence of disease relapse,except a high serum CA19-9 level.The patient is alive and regularly followed.Based on the previous literature and the present case,we believe that early diagnosis of thymic-enteric adenocarcinoma is important.CONCLUSION XELOX(capecitabine plus oxaliplatin)combined with radiotherapy is an optional therapy for inoperable thymic-enteric adenocarcinoma.展开更多
基金supported by the National Natural Science Foun-dation of China(grant numbers 81974483 and 82072589)the ChineseSocietyofClinicalOncology-HengruiCancerResearch Fund(Y-HR2020QN-0946).
文摘As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.
基金supported by the National Natural Science Foundation of China(82272676,82073011,81972562,81972566)Beijing Medical Award Foundation(YXJL-2020-0889-0106)+1 种基金Beijing Municipal Administration of Hospitals'Ascent Plan(DFL20220901)Beijing Xisike Clinical Oncology Research Foundation(Y-Roche2019/2-0076).
文摘Mucosal melanoma(MM)is extremely rare in Caucasians,whereas it is the second predominant melanoma subtype in Asian and other non-Caucasian populations.Distinct from cutaneous melanoma in terms of epidemiology,biology,and molecular characteristics,MM is characterized by more aggressive biological behavior,lower mutational burden,more chromosomal structure variants,and poorer prognosis.Because of the rarity of MM,its biological features are not fully understood,and potential novel therapies are less well depicted.Whereas immunotherapy has shown encouraging efficacy for cutaneous melanoma,its efficacy in MM is unclear due to limited sample sizes in clinical trials.Thus,in this review,we describe the epidemiological,clinical,and molecular features of MM and summarize the efficacies of different immunotherapies for MM,including immune checkpoint inhibitors,vaccines,oncolytic virus therapy,adoptive T-cell therapy,and various combination therapies.
文摘BACKGROUND Antiangiogenic agents(AAs)are increasingly used to treat malignant tumors and have been associated with gastrointestinal(GI)bleeding and perforation.Elective surgeries and endoscopy are recommended to be delayed for 31 d until after AAs treatment.Data regarding the safety of endoscopy while on antiangiogenic agents is extremely limited.No guidelines are in place to address the concern about withholding these anti-angiogenic drugs.AIM To evaluate the risks of endoscopy in patients on antiangiogenic agents from 2015 to 2020 at our institution.METHODS This is a single centered retrospective study approved by the institutional review board statement of the institution.Patients that underwent endoscopy within 28 d of antiangiogenic agents’treatment were included in the study.Primary outcome of interest was death,and secondary outcomes included perforation and GI bleeding.Data were analyzed utilizing descriptive statistics.Fifty-nine patients were included in the final analysis and a total of eighty-five procedures were performed that were characterized as low risk and high risk.RESULTS Among the 59 patients a total of 85 endoscopic procedures were performed with 24(28.2%)categorized as high-risk and 61(71.8%)procedures as low-risk.Of the total number of patients,(50%)were on bevacizumab and the rest were on imatinib(11.7%),lenvatinib(6.7%)and,ramucirumab(5%).The average duration between administration of AAs and the performance of endoscopic procedures was 9.9 d.No procedure-related adverse events were noted among our study population.We did observe two deaths with one patient,on lenvatinib for metastatic hepatocellular carcinoma,who had persistent bleeding despite esophageal variceal banding and died 4 d later from hemorrhagic shock.Another patient was diagnosed with acute myeloid leukemia died 24 d after an esophagogastroduodenoscopy with biopsy after transition to comfort care.CONCLUSION As per this single center retrospective study,the rate of endoscopic procedure-related adverse events and death within 28 d of AA administration appears to be low.
基金Supported by RFBR according to the research project,No.18-315-00434
文摘Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension(PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The Pub Med database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: "liver cirrhosis", "portal hypertension", "pathogenesis", "angiogenesis", and "antiangiogenic therapy". Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studie donly in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.
文摘● AIM: To evaluate the clinical efficacy and safety of ranibizumab for wet age-related macular degeneration(w AMD) in Chinese patients and to determine the mean number of injections administered over one year of follow-up. ● METHODS: This single centre, retrospective observational case series study included data from 121 patients with w AMD(121 eyes) who were diagnosed by indirect ophthalmoscopy, fluorescence fundus angiography(FFA), indocyanine green angiography, and optical coherence tomography. Ranibizumab was injected into the vitreous cavities once per month for 3 mo and as needed afterwards. Changes in visual acuity and central foveal thickness(CFT) during the follow-up period were compared, and the mean number of injections over the year was calculated. Patients with one or more adverse events related to the drugs and injections were recorded for further adverse events analysis. ● RESULTS: The study population included 70 males and 51 females aged between 50 and 87y(mean: 71.32±9.41y). The mean number of injections over the first year was 5±1(range: 3-9). The mean best-corrected visual acuity by Early Treatment Diabetic Retinopathy Study increased from 43.2±19.3(95%CI: 39.8-46.7) at baseline to 51.7±20.1(95%CI: 48.1-55.3), and CFT decreased from 526.5±277.0 μm(95%CI: 476.6-576.4) to 258.2±161.6 μm(95%CI: 229.2-287.3) at 12 mo. The differences were statistically significant(P<0.001). Visual acuity significantly improved in 34.1% of the patients(38 eyes), stabilized in 66.1% of the patients(80 eyes), and significantly decreased in 2.5% of the patients(3 eyes). CFT at baseline was an independent risk factor of decreased CFT and increased visual acuity. None of the patients had severe adverse events during the follow-up period.● CONCLUSION: Ranibizumab can effectively control disease progression and improve visual acuity in patients with w AMD. The disease conditions of most patients stabilized after a one-year treatment with an average of 5 injections.
文摘BACKGROUND Although hepatocellular carcinoma(HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected results.AIM To uncover immunohistochemical(IHC) aspects of angiogenesis in HCC.METHODS A retrospective cohort study was performed and 50 cases of HCC were randomly selected. The angiogenesis particularities were evaluated based on the IHC markers Cyclooxygenase-2(COX-2), vascular endothelial growth factor(VEGF) A and the endothelial area(EA) was counted using the antibodies CD31 and CD105.RESULTS The angiogenic phenotype evaluated with VEGF-A was more expressed in small tumors without vascular invasion(pT1), whereas COX-2 was rather expressed in dedifferentiated tumors developed in non-cirrhotic liver. The CD31-related EA value decreased in parallel with increasing COX-2 intensity but was higher in HCC cases developed in patients with cirrhosis. The CD105-related EA was higher in tumors developed in patients without associated hepatitis.CONCLUSION In patients with HCC developed in cirrhosis, the newly formed vessels are rather immature and their genesis is mediated via VEGF. In patients with non-cirrhotic liver, COX-2 intensity and number of mature neoformed vessels increases in parallel with HCC dedifferentiation.
基金funded by Universiti Sains Malaysia Research University(RU)Grant(1001/PFARMASI/813021)
文摘Objective:Toinvestigate the anti-angiogenic activity and antioxidant properties of Myristica fragrans（M.fragrans）（nutmeg） and Morinda citrifolia（M.citrifolia）（mengkudu） oils. Methods:The nutmeg and megkudu essential oils were obtained by steam distillation. The antioxidant activities of both essenlial oils were delermined by beta-carotene/ linoleic acid bleaching assay and reducing power while the anti-angiogenic activity was investigated using rat aortic ring assay using various concentrations.Results:The results showed that nutmeg oil has higher antioxidant activity than mengkudu oil.The nutmeg oil effectively inhibited the oxidation of linoleic acid with（88.68±0.1）%while the inhibition percentage of oxidation of linoleic acid of the mengkudu oil is（69.44±0.4）%.The nutmeg oil and mengkudu oil showed reducing power with an EC<sub>50</sub> value of 181.4μg/mL and 3 043.0μg/mL,respectively.The anliangiogenic activity of nutmeg oil showed significant antiangiogenic activity with IC<sub>50</sub> of 77.64μg/mL comparing to mengkudu oil which exhibits IC<sub>50</sub> of 109.30μg/mL.Conclusion:Bioactive compound（s） will be isolated from the nutmeg essential oil to be developed as antiangiogenic drugs.
文摘Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential collaborations among researchers all over the world.In this article,10 more questions are presented as followed.Question 57.What are the major stresses that drive the formation,progression,and metastasis of a cancer? Question 58.What is the mechanism responsible for altering an acidic intracellular pH and a basic extracellular pH in normal tissue cells to a basic intracellular pH and an acidic extracellular pH in cancer cells,a fundamental and yet largely ignored phenomenon? Question 59.Where are the tumor-associated plasma microRNAs from in cancer patients? Question 60.Can we identify mechanisms employed by tumor subpopulations to evade standard therapies and seed relapse/metastatic tumors before treatment? Question 61.Why are mutation rates in epidermal growth factor receptor(EGFR) and erb-b2 receptor tyrosine kinase 2(ERBB2) higher in lung cancer from never smokers than that from smokers? Question 62.Does tumor vasculogenic mimicry contribute to the resistance against antiangiogenic therapy in renal cancer? Question 63.What molecular targeted drugs would be effective for non-clear cell renal cell carcinoma(RCC),especially metastatic papillary RCC and chromophobe RCC? Question 64.Can it be more effective by targeting both the vascular endothelial growth factor receptor(VEGFR) and MET signaling pathways in sporadic metastatic papillary renal cell carcinoma(RCC)? Question 65.What are the predictive biomarkers that may be used to identify the renal cell carcinoma(RCC) patients who can benefit from immune checkpoint inhibitor treatment? Question 66.How do we identify predictive molecular biomarkers to stratify clear cell renal cell carcinoma patients for targeted therapies?
文摘Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77.How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79. What are the true beneficial mechanisms of antiangiogenic therapy in cancer patients? Question 80. How to approach the complex mechanisms of interplay among various cellular and molecular components in the tumor microenvironment? Question 81. Can tissue oxygenation improve the efficacy of conventional chemotherapy on cancer? Question 82. Can tissue oxygenation improve the efficacy of radiotherapy on digestive system tumors including liver cancer? Question 83. Can we integrate metabolic priming into multimodal management of liver cancer? Question 84. Has the limit of anti-androgen strategy in prostate cancer treatment been reached by the new generation of anti-androgen drugs? Question 85. Can we identify individuals with early-stage cancers via analyzing their clinical and non-clinical information collected from social media, shopping history, and clinical, pathological, and molecular traces?
基金supported financially by the Bureau of Science and Technology of Kunming City.
文摘Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and the absolute stereochemistry of 1 was determined by single crystal X-ray experiment.Compound 4 showed antiangiogenic activity evaluated by a zebrafish model and apoptosis-inducing effect on A549 lung cancer cells.
文摘Recently,follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers.In this context,we hypothesized that degarelix,a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer,may have antiangiogenic effects via its capacity to block follicle stimulating hormone(FSH)production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens.The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment.Degarelix induced a rapid decrease in FSH level.This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year.Contrast-enhanced ultrasonography demonstrated reduction of tumor vas-clature.This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug.
文摘Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi-zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.
文摘Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).
基金supported by the General Programs of the National Natural Science Foundation of China(No.81171998,81472667,and 81461148021)the National Science and Technology Major Project for "Major New Drugs Innovation and Development"(No.2013ZX09509103)supported by the General Programs of the National Natural Science Foundation of China(No. 81272529)
文摘Background:Endostatin(ES) is a well-established potent endogenous antiangiogenic factor.An ES variant,called zinc-binding protein-ES(ZBP-ES),is clinically available;however,its use is limited by rapid renal clearance and short residence time.PEGylation has been exploited to overcome these shortcomings,and mono-PEGylated ES(called M_2ES) as well as mono-PEGylated ZBP-ES(MZBP-ES) are developed in our study.This study aimed to compare the biophysical properties and biological effects of M_2ES and MZBP-ES to evaluate their druggability.Methods:Circular dichroism and tryptophan emission fluorescence were used to monitor the conformational changes of M_2ES and MZBP-ES.Their resistance to trypsin digestion and guanidinium chloride(GdmCl)-induced unfolding was examined by Coomassie staining and tryptophan emission fluorescence,respectively.The biological effects of M_2ES and MZBP-ES on endothelial cell migration were evaluated using Transwell migration and wound healing assays,and the uptake of M_2ES and MZBP-ES in endothelial cells was also compared by Western blotting and immunofluorescence.Results:Structural analyses revealed that M_2ES has a more compact tertiary structure than MZBP-ES.Moreover,M_2ES was more resistant to trypsin digestion and GdmCI-induced unfolding compared with MZBP-ES.In addition,although M_2ES and MZBP-ES showed comparable levels of inhibiting transwell migration and wound healing of endothelial cells,M_2ES displayed an increased ability to enter cells compared with MZBP-ES,possibly caused by the enhanced interaction with nucleolin.Conclusions:M_2ES has a more compact tertiary structure,is more stable for trypsin digestion and GdmCI-induced unfolding,exhibits increased cellular uptake and shows equivalent inhibitory effects on cell migration relative to MZBP-ES,indicating that M_2ES is a more promising candidate for anticancer drug development compared with MZBP-ES.
文摘BACKGROUND Squamous cell carcinoma (SCC) is one the most common subtypes of non-small cell lung cancer, yet the treatment options for it remain limited. Here, we report a case of advanced SCC and review the related literature focusing on the multiline therapy method. CASE SUMMARY We report the case of a 45-year-old man with advanced SCC who was deemed inoperable at the time of advanced SCC diagnosis. The patient had been referred to our hospital in April 2013 with complaints of a stuffy feeling in the chest, dyspnea, and pain in the right shoulder lasting for 1 mo. Physical examination found no obvious abnormalities, except for lower breath sound in the right lower lung. Laboratory data were within normal limits. Immunohistochemistry analysis of the tumor tissue showed CK5/6 (+), p63 (+), CD56 (+), and Ki-67 (+, approximately 30%), and genetic testing detected no EGFR mutation. He received a multiline treatment that included chemotherapy, radiotherapy, targeted therapy, and antiangiogenic therapy. After more than 5-year comprehensive treatment, the patient remains alive. CONCLUSION This typical case highlights the importance of appropriate multiline therapy for those patients with advanced SCC.
文摘Metastatic renal cell cancer(mRCC)management has undergone a paradigm shift in recent decades.The first revolution came with the emergence of vascular endothelial growth factor inhibitors;there was a second wave with the unprecedented success of checkpoint inhibitors,and then the latest approach,which is becoming the new care standard in mRCC,of combining these two strategies in different ways.Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival(PFS),overall survival(OS),and objective response rate(ORR)in intermediate and high-risk patients.However,several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place,and so far,the only one for nivolumab/ipilimumab is the frontline setting.The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembrolizumab/axitinib over sunitinib in favorable-risk mRCC,suggesting that it should no longer be the first line of choice in low-risk patients.Finally,the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS,OS,and ORR,providing a new first-line option among all International Metastatic RCC Database Consortium risk patients.Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib,cabozantinib/atezolizumab,and lenvatinib/pembrolizumab,providing promising grounds upon which to start phase III studies.In addition,other works are using novel therapeutic agents with different mechanisms of action,including telaglenastat(a glutaminase inhibitor),entinostat[an inhibitor of histone deacetylases(HDACs)],and olaparib and talazoparib,poly(ADP-ribose)polymerase inhibitors widely used in other tumors.However,some questions regarding mRCC management still need to be addressed,such as head-to-head comparisons between the current options,treatment sequencing,non-clear cell mRCC,and the role of biomarkers to ascertain the best treatment choice.
文摘BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.
文摘Endometriosis is an inflammatory oestrogen dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The modern advance in treatment of endometriosis management is tackling the debilitating pain it causes, besides the infertility in patients desiring fertility in reproductive age group. This can be achieved by surgical or medical means, although in most cases a combination of both treatments is required. Usually, long term treatment is required in most cases. Unfortunately in most cases, pain symptoms recur between 6months and 12 months once treatment is stopped. A lot of research has gone in understanding the pathogenesis and further medical management of endometriosis besides surgery to be useful in relieving pain and use in patients desiring fertility besides hormonal treatments used earlier like hormonal contraceptives (oral, transdermal or vaginal administration), progestogens, danazol, Gonadotrophic releasing hormone agonist (GnRH), aromatase inhibitors. Newer agents like antiangiogenic drugs, phytochemical agents like resveratrol, TNF-α inhibitors, GnRH antagonists like egalogolix, statins, antiinflammatory agents like COX2 Inhibitors and PPARγ inhibitors like pioglitazone etc., with recent work of combined efficacy of telmesartan of both PPARγ partial agonism along with angiotensin 1 receptor agonism having more efficacy, role of immunomodulators like rapamycin, lipoxin 4 and pentoxyphylline, GnRH antagonists like egalogolix are still under study undergoing phase III trials although preliminary results show promising results with fewer side effects as compared to similar duration of GnRH agonist and much less BMD side effects. Increasing number of trials show the safety of SPRM’s, along with efficacy although disadvantage is suppression of fertility so cannot be used for women desiring fertility. Currently, only mifepristone and ulipristal have received FDA approval for indication in fibroid treatment, MTP and not for endometriosis as yet. The advantages and disadvantages of all the recent advances are discussed in an update in the pathophysiology as well medical treatment of endometriosis.
基金Supported by National Natural Science Foundation of China,No.30670603
文摘AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126and thalidomide for solid tumors.
文摘BACKGROUND Thymic-enteric adenocarcinoma with positive expression of CDX2 and CK20 is rare in adults,with only 16 reported cases.However,standard treatment options for this type of thymic adenocarcinoma has not yet been established.Therefore,we report a case of stage IV thymic-enteric adenocarcinoma treated with radiotherapy,chemotherapy,and anti-angiogenesis therapy.CASE SUMMARY We report a case of thymic-enteric adenocarcinoma occurring in a 44-year-old woman.The tumor was considered unresectable owing to its invasiveness.The patient was treated with six cycles of oxaliplatin(130 mg/m^(2),day 1)and capecitabine(1000 mg/m^(2) BID,days 1-14).During the first three cycles of chemotherapy,concurrent radiotherapy(60 Gy/30 fractions)and anti-angiogenic therapy using apatinib were recommended.The primary tumor achieved partial remission based on the Response Evaluation Criteria in Solid Tumors.During follow-up,there was no evidence of disease relapse,except a high serum CA19-9 level.The patient is alive and regularly followed.Based on the previous literature and the present case,we believe that early diagnosis of thymic-enteric adenocarcinoma is important.CONCLUSION XELOX(capecitabine plus oxaliplatin)combined with radiotherapy is an optional therapy for inoperable thymic-enteric adenocarcinoma.
