Glycyrrhetinic acid(GA)sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver,however,the limitation of commonly used macromolecular GA modification approaches as well as ...Glycyrrhetinic acid(GA)sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver,however,the limitation of commonly used macromolecular GA modification approaches as well as the application gap across various vector have constrained its use.In this study,we proposed a novel perspective to break out,disulfide bonds(SS)were employed as linkage to facilitate GA modification,which allowed further connections with various carriers,while provided additional glutathione(GSH)-responsive property.The superiority of GA-disulfide conjunction was validated using mesoporous silica nanoparticles(MSN)as model carriers,chemotherapeutic drug(doxorubicin)and photosensitizer(indocyanine green)were loaded into MSN-SS-GA to further achieve chemo-photothermal synergistic anti-tumor therapy.Based on results from multiple evaluations,the GA-disulfide drafted MSN(DI/MSN-SS-GA)demonstrated expected liver tumor targeting effect and exhibited GSH-stimuli release property to reduce preleakage.Taken together,this study presents an effective chemo-photothermal therapy for liver cancer(88.26%),offers a potential,robust and straightforward strategy on GA application for enhancing liver targeting therapy.展开更多
For patients with primary stage IVB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review...For patients with primary stage IVB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords： ＂uterine cervical cancer＂, ＂chemotherapy＂, and ＂targeted therapies＂. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase III trials. To examine the best agent to combine with cisplatin, several landmark phase III clinical trials were conducted by Gynecologic Oncology Group （GOG） and Japan Clinical Oncology Group （JCOG）. Through, GOG204 and JCOG0505, paclitaxel/cisplatin （TP） and paclitaxel/carboplatin （TC） are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival （OS）. Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only modest gains in OS, particularly for patients with multiple poor prognostic factors. Therefore, it is crucial to consider not only the survival benefit, but also the minimization of treatment toxicity, and maximization of quality of life （QOL）.展开更多
To investigate the radioimmunotherapeutic efficacy, radio-immunoconjugate 131-I-3G9, 811-I-3H11 and 131-I-NMIgG (irre levant antibody) were i.p. injected into nude mice bearing human gastric cancer xenograftes. Each a...To investigate the radioimmunotherapeutic efficacy, radio-immunoconjugate 131-I-3G9, 811-I-3H11 and 131-I-NMIgG (irre levant antibody) were i.p. injected into nude mice bearing human gastric cancer xenograftes. Each animal received a single doses of 555MBq. Over 14 days the accumulative absorbed doses in tumors were 13.7 Gy for 131-I-3H11 and 12.17 Gy for 131-I-3G9. Both were significantly higher than that for 131-I-NMIgG (3.23 Gy). Thera peutic efficacy appeared most sharply from 2 to 3 weeks after injection. The inhibition ratio of tumor were 86% and 70% for 131-I-3H11 and 131-I-3G9 respectively. Histopathological evidance indicated that in tumor tissues radioactive damage was showed as karyopyknosis, karyorrhexis and necrosis or partial disappearance of tumor cells, while in the other tissues no radioactive damage was observed. WBC counts of all animals did not show significant difference before and after treatment, which indicated that the haemopoietic function of bone marrow was not affected.展开更多
Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found ...Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found at the time of diagnosis.[1] Surgical resection is now the standard treatment and also the only potentially curative treatment for resectable lesions.展开更多
SHP2 is the first identified oncogenic tyrosine phosphatase that promotes colorectal cancer(CRC)progression,and it is consistently overexpressed in CRC.It facilitates CRC oncogenesis by mediating downstream signaling ...SHP2 is the first identified oncogenic tyrosine phosphatase that promotes colorectal cancer(CRC)progression,and it is consistently overexpressed in CRC.It facilitates CRC oncogenesis by mediating downstream signaling cascades of receptor tyrosine kinases,including the RAS/ERK,JAK/STAT,and PI3K/AKT pathways,which are clinically associated with poor prognosis.Furthermore,SHP2 orchestrates immunosuppressive signaling networks by impairing cytotoxic T cell infiltration and changing the phenotype of tumor-associated macrophages within the tumor microenvironment(TME).Targeting SHP2 represents a dual therapeutic strategy in CRC:It concurrently regulates RTK signaling and reprograms the immunosuppressive TME.SHP2 inhibitors,administered both as monotherapy and in combination regimens,have advanced into clinical trial phases.Consequently,SHP2 serves as both a molecular target for precision oncology and an immunomodulatory node,positioning it as a high-priority candidate for CRC treatment.展开更多
Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address t...Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)interaction.This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and trials.TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53.MDM2 and TP53 activity is tightly regulated.However,cancerous breast cells overexpress MDM2 through five hypothesized mechanisms.Consequently,TP53 levels decrease with increased tumor cell proliferation.Three strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated TP53.MDM2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy cells.Few clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.展开更多
Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these app...Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.展开更多
Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agen...Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agents and small-molecule agents has significantly advanced our ability to target the disease more effectively[2].In the current review,we summarize the outcomes of targeted therapies in rosacea,mainly focusing on interleukin(IL)-17 inhibitors and Janus kinase(JAK)inhibitors.展开更多
BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a...BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a 17-year-old female patient presenting with in-termittent,non-cyclical vaginal bleeding and associated lower abdominal pain.Pelvic magnetic resonance imaging and additional examinations led to the dia-gnosis of cervical rhabdomyosarcoma.The primary treatment options for uterine cervical rhabdomyosarcoma include surgery,with or without adjuvant chemo-therapy and radiotherapy.This patient underwent surgery followed by a posto-perative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab.After 19 months of follow-up,the patient showed no signs of re-currence and maintained good overall health.Given the rarity of cervix rhab-domyosarcoma,this case is presented to provide insights into the diagnosis and treatment of this condition.CONCLUSION This suggests that bevacizumab may demonstrate potential efficacy in the treat-ment of cervical rhabdomyosarcoma.In the future,targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.展开更多
Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms...Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms, requiring histopathology for diagnosis. Surgery remains the standard of care for localized disease, serving both diagnostic and therapeutic purposes, though adjuvant chemotherapy has shown limited efficacy. In metastatic CDC, the gemcitabine-cisplatin regimen is commonly used due to its resemblance to urothelial cancer and supportive data from prospective studies. Newer therapies offer promise in advanced cases. Immune checkpoint inhibitors, such as nivolumab alone or with ipilimumab, have shown benefits in patients with high PD-L1 expression. Targeted therapies like cabozantinib demonstrated efficacy and safety as first-line treatments in phase II trials, while sunitinib and sorafenib have shown responses in various case reports and cohorts. However, combining chemotherapy with bevacizumab did not improve outcomes in phase II trials. Despite therapeutic advances in urothelial cancers and clear cell renal tumors, the CDC entity remains a challenging malignancy, emphasizing the need for continued research to understand the true efficacy of treatment and to prolong survival in advanced disease.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantati...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.展开更多
Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in...Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.展开更多
Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown pr...Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.展开更多
This article systematically reviews the application of biomimetic nanotechnology in targeted therapy for triple-negative breast cancer(TNBC).TNBC poses significant challenges for conventional treatments due to the lac...This article systematically reviews the application of biomimetic nanotechnology in targeted therapy for triple-negative breast cancer(TNBC).TNBC poses significant challenges for conventional treatments due to the lack of defined therapeutic targets,chemotherapy resistance,and a complex immunosuppressive microenvironment.Biomimetic nanotechnology,by mimicking the functional properties of biological structures(e.g.,cell membranes,exosomes),has significantly enhanced drug delivery efficiency,targeting precision,and anti-tumor immune responses.This review focuses on the design strategies of biomimetic nanocarriers(including cell membrane-coated nanoparticles,engineered exosomes,and biomimetic synthetic materials)and their innovative applications in TNBC therapy:(1)Targeted delivery systems that overcome tumor barriers and reduce systemic toxicity;(2)Photothermal therapy combined with immunomodulation for precise treatment and immune activation;(3)Tumor microenvironment regulation(e.g.,vascular normalization,pH neutralization,immunosuppression reversal).Studies demonstrate that biomimetic nanotechnology significantly improves TNBC treatment efficacy through multimodal synergistic mechanisms(e.g.,chemo-photothermal-immunotherapy).However,challenges such as scalable production,long-term safety,and personalized adaptation remain for clinical translation.Future research should integrate artificial intelligence for optimized design and dynamic imaging technologies to advance biomimetic nanomedicines toward clinical applications.展开更多
The emerging messenger RNA(mRNA)nanomedicines have sprung up for disease treatment.Developing targeted mRNA nanomedicines has become a thrilling research hotspot in recent years,as they can be precisely delivered to s...The emerging messenger RNA(mRNA)nanomedicines have sprung up for disease treatment.Developing targeted mRNA nanomedicines has become a thrilling research hotspot in recent years,as they can be precisely delivered to specific organs or tissues to enhance efficiency and avoid side effects.Herein,we give a comprehensive review on the latest research progress of mRNA nanomedicines with targeting functions.mRNA and its carriers are first described in detail.Then,mechanisms of passive targeting,endogenous targeting,and active targeting are outlined,with a focus on various biological barriers that mRNA may encounter during in vivo delivery.Next,emphasis is placed on summarizing mRNA-based organtargeting strategies.Lastly,the advantages and challenges of mRNA nanomedicines in clinical translation are mentioned.This review is expected to inspire researchers in this field and drive further development of mRNA targeting technology.展开更多
Hemoptysis is a severe complication of pulmonary hypertension (PH) with a low in- cidence of 6%-11%.^([1-4])Although occurring in all forms of PH,it is more commonly seen in pulmonary arterial hypertension (PAH),assoc...Hemoptysis is a severe complication of pulmonary hypertension (PH) with a low in- cidence of 6%-11%.^([1-4])Although occurring in all forms of PH,it is more commonly seen in pulmonary arterial hypertension (PAH),associated with congenital heart disease (PAH-CHD).^([5,6])Since enlarged bronchial arteries are a frequent source of pulmonary bleeding,the primary treatment focuses on bronchial artery embolization (BAE),especially for chronic thromboembolic pulmonary hypertension (CTEPH) patients^([7,8]).However,there is disagreement regarding medical therapy,which has received little attention in the recently published PH guidelines.^([5,6])展开更多
BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and progno...BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.展开更多
Osteopontin(OPN),a key extracellular matrix protein,promotes gastrointestinal tumor progression by activating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.OPN enhances tumor proliferation and s...Osteopontin(OPN),a key extracellular matrix protein,promotes gastrointestinal tumor progression by activating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.OPN enhances tumor proliferation and survival through mechanistic target of rapamycin and B-cell lymphoma 2 upregulation(e.g.,via denticleless E3 ubiquitin protein ligase homolog in hepatocellular carcinoma)and drives metastasis via PI3K/AKT-mediated epithelial-mesenchymal transition and androgen receptor(AR)activation(e.g.,via the OPN-RAN-AR axis in pancreatic cancer).Additionally,OPN induces chemoresistance by activating anti-apoptotic proteins(e.g.,XIAP via CXCR3/PI3K/AKT in colorectal cancer)and remodels the tumor microenvironment through VEGF-dependent angiogenesis and cluster of differentiation 44-PI3K/AKT-mediated immune evasion.Its interaction with TLR4,WNT,and other pathways amplifies oncogenic effects.Therapies targeting the OPN-PI3K/AKT axis(e.g.,PI3K inhibitors like LY294002)or combination treatments(e.g.,with EGFR-TKIs)show promise for reversing drug resistance.Future research should focus on OPN isoform specificity,clinical translation,and interactions with autophagy and long non-coding RNAs to refine precision therapies.This review summarizes recent advances in understanding the molecular mechanisms,therapeutic targets,and clinical challenges of the OPN-PI3K/AKT axis in gastrointestinal tumors,providing a foundation for overcoming resistance and developing precision therapies.展开更多
Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD),but they still face challenges in successfully passing through ...Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD),but they still face challenges in successfully passing through the harsh gastrointestinal environment and intestinal mucus barrier.To overcome the gastrointestinal barriers for oral drug delivery mentioned above,a“spore-like”oral nanodrug delivery platform(Cur/COS/SC NPs)has been developed.Firstly,chitooligosaccharides(COS)are encapsulated on the surface of Curcumin nanoparticles(Cur NPs)to form carrier-free nanoparticles(Cur/COS NPs).Subsequently,inspired by the natural high resistance of spore coat(SC),SC is chosen as the“protective umbrella”to encapsulate Cur/COS NPs for precision targeted therapy of IBD.After oral administration,SC can effectively protect NPs through the rugged gastrointestinal environment and exhibit excellent intestinal mucus penetration characteristics.Moreover,the negatively-charged Cur/COS/SC NPs specifically target positivelycharged inflamed colon via electrostatic interactions.It is demonstrated that Cur/COS/SC NPs can promote the expression of tight junction proteins,inhibit aberrant activation of the Toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway,and downregulate the levels of pro-inflammatory factors,exhibiting excellent anti-inflammatory effects.Notably,it is found that Cur/COS/SC NPs can significantly increase the richness and diversity of gut microbiota,and restore the homeostasis of gut microbiota by inhibiting pathogenic bacteria and promoting probiotics.Hence,Cur/COS/SC NPs provide a safe,efficient,and feasible new strategy for IBD treatment.展开更多
In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using networ...In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using network metaanalysis methodology.We focus specifically on the potential advantages and role of HAIC in the treatment algorithm for advanced HCC.However,there remains numerous knowledge gaps before the role of HAIC can be established.There is significant heterogeneity of HAIC regimes with difficult interpretation of the clinical outcomes.Additionally,there is a lack of direct comparative data between HAIC,systemic chemotherapy,novel immunotherapies and targeted therapies.The underlying biochemical mechanisms that might explain the efficacy of HAIC and its effect on the HCC microenvironment requires further research.In the developing era of nanotechnology and targeted drug delivery systems,there is potential for integration of HAIC with novel technologies to effectively treat advanced HCC whilst minimising systemic complications.展开更多
基金funded by Research Project of Department of Education of Liaoning Province(No.LJKMZ20221363,China)。
文摘Glycyrrhetinic acid(GA)sheds new light on liver-targeted therapy due to high-specific accumulation to GA receptors in liver,however,the limitation of commonly used macromolecular GA modification approaches as well as the application gap across various vector have constrained its use.In this study,we proposed a novel perspective to break out,disulfide bonds(SS)were employed as linkage to facilitate GA modification,which allowed further connections with various carriers,while provided additional glutathione(GSH)-responsive property.The superiority of GA-disulfide conjunction was validated using mesoporous silica nanoparticles(MSN)as model carriers,chemotherapeutic drug(doxorubicin)and photosensitizer(indocyanine green)were loaded into MSN-SS-GA to further achieve chemo-photothermal synergistic anti-tumor therapy.Based on results from multiple evaluations,the GA-disulfide drafted MSN(DI/MSN-SS-GA)demonstrated expected liver tumor targeting effect and exhibited GSH-stimuli release property to reduce preleakage.Taken together,this study presents an effective chemo-photothermal therapy for liver cancer(88.26%),offers a potential,robust and straightforward strategy on GA application for enhancing liver targeting therapy.
文摘For patients with primary stage IVB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords： ＂uterine cervical cancer＂, ＂chemotherapy＂, and ＂targeted therapies＂. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase III trials. To examine the best agent to combine with cisplatin, several landmark phase III clinical trials were conducted by Gynecologic Oncology Group （GOG） and Japan Clinical Oncology Group （JCOG）. Through, GOG204 and JCOG0505, paclitaxel/cisplatin （TP） and paclitaxel/carboplatin （TC） are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival （OS）. Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only modest gains in OS, particularly for patients with multiple poor prognostic factors. Therefore, it is crucial to consider not only the survival benefit, but also the minimization of treatment toxicity, and maximization of quality of life （QOL）.
文摘To investigate the radioimmunotherapeutic efficacy, radio-immunoconjugate 131-I-3G9, 811-I-3H11 and 131-I-NMIgG (irre levant antibody) were i.p. injected into nude mice bearing human gastric cancer xenograftes. Each animal received a single doses of 555MBq. Over 14 days the accumulative absorbed doses in tumors were 13.7 Gy for 131-I-3H11 and 12.17 Gy for 131-I-3G9. Both were significantly higher than that for 131-I-NMIgG (3.23 Gy). Thera peutic efficacy appeared most sharply from 2 to 3 weeks after injection. The inhibition ratio of tumor were 86% and 70% for 131-I-3H11 and 131-I-3G9 respectively. Histopathological evidance indicated that in tumor tissues radioactive damage was showed as karyopyknosis, karyorrhexis and necrosis or partial disappearance of tumor cells, while in the other tissues no radioactive damage was observed. WBC counts of all animals did not show significant difference before and after treatment, which indicated that the haemopoietic function of bone marrow was not affected.
文摘Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found at the time of diagnosis.[1] Surgical resection is now the standard treatment and also the only potentially curative treatment for resectable lesions.
基金Supported by Zhejiang Provincial Natural Science Foundation for Youths,No.QN25H160012Zhejiang Medical and Health Science and Technology Plan,No.2023RC006.
文摘SHP2 is the first identified oncogenic tyrosine phosphatase that promotes colorectal cancer(CRC)progression,and it is consistently overexpressed in CRC.It facilitates CRC oncogenesis by mediating downstream signaling cascades of receptor tyrosine kinases,including the RAS/ERK,JAK/STAT,and PI3K/AKT pathways,which are clinically associated with poor prognosis.Furthermore,SHP2 orchestrates immunosuppressive signaling networks by impairing cytotoxic T cell infiltration and changing the phenotype of tumor-associated macrophages within the tumor microenvironment(TME).Targeting SHP2 represents a dual therapeutic strategy in CRC:It concurrently regulates RTK signaling and reprograms the immunosuppressive TME.SHP2 inhibitors,administered both as monotherapy and in combination regimens,have advanced into clinical trial phases.Consequently,SHP2 serves as both a molecular target for precision oncology and an immunomodulatory node,positioning it as a high-priority candidate for CRC treatment.
文摘Breast cancer is a significant global concern,with limited effective treatment options.Therefore,therapies with high efficacy and low complications,unlike the existing chemotherapies,are urgently required.To address this issue,advances have been made in therapies targeting molecular pathways related to the murine double minute 2 protooncogene(MDM2)-tumor proteinp53(TP53)interaction.This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells,as evidenced by clinical studies,reviews,and trials.TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53.MDM2 and TP53 activity is tightly regulated.However,cancerous breast cells overexpress MDM2 through five hypothesized mechanisms.Consequently,TP53 levels decrease with increased tumor cell proliferation.Three strategies have been identified for controlling MDM2 upregulation in cells with wild-type or mutated TP53.MDM2 inhibitors(MDM2i)are administered in combination with existing chemotherapies to reduce their effects on healthy cells.Few clinical and preclinical studies have been conducted using MDM2i,which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.
文摘Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.
文摘Dear Editor,Rosacea is characterized by persistent or transient erythema,papules,pustules,telangiectasia,and/or phymatous lesions[1].Although multiple treatments are available for rosacea,the advent of biological agents and small-molecule agents has significantly advanced our ability to target the disease more effectively[2].In the current review,we summarize the outcomes of targeted therapies in rosacea,mainly focusing on interleukin(IL)-17 inhibitors and Janus kinase(JAK)inhibitors.
文摘BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a 17-year-old female patient presenting with in-termittent,non-cyclical vaginal bleeding and associated lower abdominal pain.Pelvic magnetic resonance imaging and additional examinations led to the dia-gnosis of cervical rhabdomyosarcoma.The primary treatment options for uterine cervical rhabdomyosarcoma include surgery,with or without adjuvant chemo-therapy and radiotherapy.This patient underwent surgery followed by a posto-perative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab.After 19 months of follow-up,the patient showed no signs of re-currence and maintained good overall health.Given the rarity of cervix rhab-domyosarcoma,this case is presented to provide insights into the diagnosis and treatment of this condition.CONCLUSION This suggests that bevacizumab may demonstrate potential efficacy in the treat-ment of cervical rhabdomyosarcoma.In the future,targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.
文摘Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms, requiring histopathology for diagnosis. Surgery remains the standard of care for localized disease, serving both diagnostic and therapeutic purposes, though adjuvant chemotherapy has shown limited efficacy. In metastatic CDC, the gemcitabine-cisplatin regimen is commonly used due to its resemblance to urothelial cancer and supportive data from prospective studies. Newer therapies offer promise in advanced cases. Immune checkpoint inhibitors, such as nivolumab alone or with ipilimumab, have shown benefits in patients with high PD-L1 expression. Targeted therapies like cabozantinib demonstrated efficacy and safety as first-line treatments in phase II trials, while sunitinib and sorafenib have shown responses in various case reports and cohorts. However, combining chemotherapy with bevacizumab did not improve outcomes in phase II trials. Despite therapeutic advances in urothelial cancers and clear cell renal tumors, the CDC entity remains a challenging malignancy, emphasizing the need for continued research to understand the true efficacy of treatment and to prolong survival in advanced disease.
基金Supported by the National Natural Science Foundation of China,No.82270634Third Affiliated Hospital of Naval Medical University,No.tf2024yzyy01.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.
文摘Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.
基金Supported by 2023 Hebei Provincial Medical Scientific Research Project Plan,No.20231304.
文摘Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.
文摘This article systematically reviews the application of biomimetic nanotechnology in targeted therapy for triple-negative breast cancer(TNBC).TNBC poses significant challenges for conventional treatments due to the lack of defined therapeutic targets,chemotherapy resistance,and a complex immunosuppressive microenvironment.Biomimetic nanotechnology,by mimicking the functional properties of biological structures(e.g.,cell membranes,exosomes),has significantly enhanced drug delivery efficiency,targeting precision,and anti-tumor immune responses.This review focuses on the design strategies of biomimetic nanocarriers(including cell membrane-coated nanoparticles,engineered exosomes,and biomimetic synthetic materials)and their innovative applications in TNBC therapy:(1)Targeted delivery systems that overcome tumor barriers and reduce systemic toxicity;(2)Photothermal therapy combined with immunomodulation for precise treatment and immune activation;(3)Tumor microenvironment regulation(e.g.,vascular normalization,pH neutralization,immunosuppression reversal).Studies demonstrate that biomimetic nanotechnology significantly improves TNBC treatment efficacy through multimodal synergistic mechanisms(e.g.,chemo-photothermal-immunotherapy).However,challenges such as scalable production,long-term safety,and personalized adaptation remain for clinical translation.Future research should integrate artificial intelligence for optimized design and dynamic imaging technologies to advance biomimetic nanomedicines toward clinical applications.
基金supported by the National Key Research and Development Program of China(2022YFA1105304)the National Natural Science Foundation of China(T2225003 and 61927805)+5 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)the Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB032)the Natural Science Foundation of Jiangsu Province(BK20240223)the Project of Institute of Chinese Medicine of Nanjing University(ICM2024011)the Aid Project of Nanjing Drum Tower Hospital Health,Education&Research Foundation.
文摘The emerging messenger RNA(mRNA)nanomedicines have sprung up for disease treatment.Developing targeted mRNA nanomedicines has become a thrilling research hotspot in recent years,as they can be precisely delivered to specific organs or tissues to enhance efficiency and avoid side effects.Herein,we give a comprehensive review on the latest research progress of mRNA nanomedicines with targeting functions.mRNA and its carriers are first described in detail.Then,mechanisms of passive targeting,endogenous targeting,and active targeting are outlined,with a focus on various biological barriers that mRNA may encounter during in vivo delivery.Next,emphasis is placed on summarizing mRNA-based organtargeting strategies.Lastly,the advantages and challenges of mRNA nanomedicines in clinical translation are mentioned.This review is expected to inspire researchers in this field and drive further development of mRNA targeting technology.
基金supported by Liaoning Xingliao Talent Project (Grant No. XLYC2007020)。
文摘Hemoptysis is a severe complication of pulmonary hypertension (PH) with a low in- cidence of 6%-11%.^([1-4])Although occurring in all forms of PH,it is more commonly seen in pulmonary arterial hypertension (PAH),associated with congenital heart disease (PAH-CHD).^([5,6])Since enlarged bronchial arteries are a frequent source of pulmonary bleeding,the primary treatment focuses on bronchial artery embolization (BAE),especially for chronic thromboembolic pulmonary hypertension (CTEPH) patients^([7,8]).However,there is disagreement regarding medical therapy,which has received little attention in the recently published PH guidelines.^([5,6])
基金Supported by Chongqing Young and Middle-aged Medical High-end Talents,No.YXGD202405Chongqing District and County Head Goose Talents,Chongqing Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.2024ZYYB036Chongqing Banan District Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.BNWJ202300112.
文摘BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.
基金Supported by Hongkou District Health Commission of Shanghai Municipality,No.“Hongwei”2303-10.
文摘Osteopontin(OPN),a key extracellular matrix protein,promotes gastrointestinal tumor progression by activating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.OPN enhances tumor proliferation and survival through mechanistic target of rapamycin and B-cell lymphoma 2 upregulation(e.g.,via denticleless E3 ubiquitin protein ligase homolog in hepatocellular carcinoma)and drives metastasis via PI3K/AKT-mediated epithelial-mesenchymal transition and androgen receptor(AR)activation(e.g.,via the OPN-RAN-AR axis in pancreatic cancer).Additionally,OPN induces chemoresistance by activating anti-apoptotic proteins(e.g.,XIAP via CXCR3/PI3K/AKT in colorectal cancer)and remodels the tumor microenvironment through VEGF-dependent angiogenesis and cluster of differentiation 44-PI3K/AKT-mediated immune evasion.Its interaction with TLR4,WNT,and other pathways amplifies oncogenic effects.Therapies targeting the OPN-PI3K/AKT axis(e.g.,PI3K inhibitors like LY294002)or combination treatments(e.g.,with EGFR-TKIs)show promise for reversing drug resistance.Future research should focus on OPN isoform specificity,clinical translation,and interactions with autophagy and long non-coding RNAs to refine precision therapies.This review summarizes recent advances in understanding the molecular mechanisms,therapeutic targets,and clinical challenges of the OPN-PI3K/AKT axis in gastrointestinal tumors,providing a foundation for overcoming resistance and developing precision therapies.
基金supported by the National Natural Science Foundation of China(Nos.82272847,82304417,82303529,82171333)China Postdoctoral Science Foundation(Nos.2023TQ0307,2023M743231,2023M730971)+2 种基金Science and Technology Project of Henan Province(No.242102311204)Postdoctoral Fellowship Program of CPSF(No.GZB20230675)Modern Analysis and Computer Center of Zhengzhou University.
文摘Colon-targeted oral drug delivery systems are one of the most promising therapeutic strategies for alleviating and curing inflammatory bowel disease(IBD),but they still face challenges in successfully passing through the harsh gastrointestinal environment and intestinal mucus barrier.To overcome the gastrointestinal barriers for oral drug delivery mentioned above,a“spore-like”oral nanodrug delivery platform(Cur/COS/SC NPs)has been developed.Firstly,chitooligosaccharides(COS)are encapsulated on the surface of Curcumin nanoparticles(Cur NPs)to form carrier-free nanoparticles(Cur/COS NPs).Subsequently,inspired by the natural high resistance of spore coat(SC),SC is chosen as the“protective umbrella”to encapsulate Cur/COS NPs for precision targeted therapy of IBD.After oral administration,SC can effectively protect NPs through the rugged gastrointestinal environment and exhibit excellent intestinal mucus penetration characteristics.Moreover,the negatively-charged Cur/COS/SC NPs specifically target positivelycharged inflamed colon via electrostatic interactions.It is demonstrated that Cur/COS/SC NPs can promote the expression of tight junction proteins,inhibit aberrant activation of the Toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway,and downregulate the levels of pro-inflammatory factors,exhibiting excellent anti-inflammatory effects.Notably,it is found that Cur/COS/SC NPs can significantly increase the richness and diversity of gut microbiota,and restore the homeostasis of gut microbiota by inhibiting pathogenic bacteria and promoting probiotics.Hence,Cur/COS/SC NPs provide a safe,efficient,and feasible new strategy for IBD treatment.
文摘In this manuscript,we comment on the article by Zhou et al,who assessed the efficacy of hepatic arterial infusion chemotherapy(HAIC)and its combination strategies for advanced hepatocellular carcinoma(HCC)using network metaanalysis methodology.We focus specifically on the potential advantages and role of HAIC in the treatment algorithm for advanced HCC.However,there remains numerous knowledge gaps before the role of HAIC can be established.There is significant heterogeneity of HAIC regimes with difficult interpretation of the clinical outcomes.Additionally,there is a lack of direct comparative data between HAIC,systemic chemotherapy,novel immunotherapies and targeted therapies.The underlying biochemical mechanisms that might explain the efficacy of HAIC and its effect on the HCC microenvironment requires further research.In the developing era of nanotechnology and targeted drug delivery systems,there is potential for integration of HAIC with novel technologies to effectively treat advanced HCC whilst minimising systemic complications.
