From 1975 through 1990, 199 patients with limited small cell lung cancer (LSCLC) were subjected to multimodality treatment including surgical resection combined with chemotherapy or chemoradiotherapy in our department...From 1975 through 1990, 199 patients with limited small cell lung cancer (LSCLC) were subjected to multimodality treatment including surgical resection combined with chemotherapy or chemoradiotherapy in our department. The median postoperative survival time of the 199 patients was 39 months, and the 5-year survival rate was 26%, which was decreased with increase of tumor-stage. In comparison of the survival time of patients in Stage Ⅰ and those in Stage Ⅲa, there was a significant difference (P<0.01). There were no significant differences in survival rate of 3 and 5 years between the patients receiving chemotherapy prior to or after surgical resection. The improvement in survival was documented by surgical resection combined with chemotherapy or chemoradiotherapy for LSCLC. The effect of multimodality treatment is correlated with tumor P-TNM staging, the involvement of lymph node, especially that of the mediastinal lymph node, is a negative factor influencing the prognosis. Surgical resection as an initial management, followed by chemotherapy or chemoradiotherapy may be indicated in LSCLC patients of Stage Ⅰ, Stage Ⅱ and some Stage Ⅲa as the cancer can be resected completely.展开更多
Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclu- sively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an e?ort to improve su...Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclu- sively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an e?ort to improve survival. Results from phase III randomized trials are encouraging however, they revealed 五笔字型计算机汉字输入技术 that only patients with major histopathological response will bene?t from treatment. Therefore, predic- tive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym: HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who ful?l the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not bene?t from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-e?ective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.展开更多
Spinal cord injury(SCI)is a serious traumatic disease of the central nervous system,which can give rise to the loss of motor and sensory function.Due to its complex pathological mechanism,the treatment of this disease...Spinal cord injury(SCI)is a serious traumatic disease of the central nervous system,which can give rise to the loss of motor and sensory function.Due to its complex pathological mechanism,the treatment of this disease still faces a huge challenge.Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord.Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI.In this review,hydrogel-based multimodal therapeutic strategies to repair SCI are provided,and a combination of hydrogel scaffolds and other therapeutic modalities are discussed,with particular emphasis on the repair mechanism of SCI.展开更多
A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most...A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.展开更多
BACKGROUND Laparoscopic duodenojejunostomy(LDJ) has become the standard surgical procedure for superior mesenteric artery syndrome due to its sufficient outcome in terms of safety and symptom relief. However, there ar...BACKGROUND Laparoscopic duodenojejunostomy(LDJ) has become the standard surgical procedure for superior mesenteric artery syndrome due to its sufficient outcome in terms of safety and symptom relief. However, there are only a few reports about LDJ for malignant stenosis and its indication remains uncertain.CASE SUMMARY A 77-year-old woman with a history of pancreatic cancer(PC) treated with distal pancreatectomy with en bloc resection of the transverse colon 7 mo ago was admitted for recurrent vomiting. Imaging upon admission revealed marked distention of the duodenum and a tumor around the duodenojejunal flexure. She was diagnosed with malignant stenosis caused by local recurrence of PC. LDJ was performed with an uneventful postoperative course, followed by chemotherapy which gave her 10 mo overall survival.CONCLUSION We think that LDJ is a valuable method for unresectable malignant stenosis around the duodenojejunal flexure as a part of multimodal therapy.展开更多
Objective: Combined small cell lung cancer (C-SCLC) is an uncommon subgroup of small cell lung cancer (SCLC) and few clinical data can be referred. Our study is to investigate the clinical features and prognostic...Objective: Combined small cell lung cancer (C-SCLC) is an uncommon subgroup of small cell lung cancer (SCLC) and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.Methods: Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.Results: One hundred and fourteen patients were enrolled, with a median age of 59 (range: 20-79) years old. The most common combined component was squamous cell carcinoma (52.6%). Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients (70.2%) received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival (OS) was 26.2 months. On univariate analysis, smoking (P=0.029), Karnofsky performance score (KPS) 〈80 (P=0.000), advanced TNM stage (P=0.000), no surgery (P=0.010), positive resection margin (P=0.000), positive lymph nodes ≥4 (P=0.000), positive lymph node ratio 〉10% (P=0.000) and non-multimodality treatment (P=0.004) were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉 10% were poor prognostic features. Conclusions: C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉10% are poor prognostic factors.展开更多
BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a highly malignant tumour.Hepatectomy is an effective treatment for early ICC,but postoperative recurrence greatly affects patient survival.Studies on recurrent ICC af...BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a highly malignant tumour.Hepatectomy is an effective treatment for early ICC,but postoperative recurrence greatly affects patient survival.Studies on recurrent ICC after hepatectomy are lacking.AIM To investigate the clinical characteristics of patients with recurrent ICC after hepatectomy,analyse prognostic factors and explore diagnosis and treatment strategies.METHODS A retrospective analysis was performed on all ICC patients undergoing hepatectomy from January 2013 to August 2021.Patients with postoperative recurrence were selected according to the inclusion and exclusion criteria.Cumulative overall survival was plotted by the Kaplan-Meier method,and differences were assessed by univariate survival analysis using the log-rank test.Multivariate analysis of cumulative survival was performed using the Cox proportional risk model.RESULTS During the 8-year study period,103 patients underwent ICC-related hepatectomy,and 54 exhibited postoperative recurrence.The median disease-free survival(DFS)was 6 mo,the median overall survival(OS)was 9 mo,and the cumulative OS rates at 1,2 and 3 years after the operation were 40.7%,14.8%and 7.4%,respectively.The median OS after recurrence was 4 mo,and the cumulative OS rates at 1,2 and 3 years after recurrence were 16.1%,6.7%and 3.4%,respectively.Multivariate analysis showed that alcohol consumption[hazard ratio(HR)=4.64,95%confidence interval(CI):1.53-14.04,P=0.007]and DFS<6 mo(HR=3.47,95%CI:1.59-7.60,P=0.002)were independent risk factors for the cumulative survival of patients with recurrence,while treatment after recurrence(HR=0.21,95%CI:0.08-0.55,P=0.001)was an independent protective factor.The median OS time of patients receiving multimodality therapy after recurrence of ICC was 7 mo,which was significantly higher than that of patients receiving only local therapy(3 mo),patients receiving systematic therapy(4 mo)and patients receiving the best supportive therapy(1 mo).Patients with recurrent ICC who received multimodality therapy had a significantly better long-term survival after recurrence than those who did not(P=0.026).CONCLUSION The prognosis of patients with recurrence after ICC-related hepatectomy is poor.Alcohol consumption and DFS<6 mo are independent risk factors in terms of the cumulative survival of patients with recurrence,while treatment after recurrence is an independent protective factor.Multimodality therapy can effectively improve the prognosis of patients.展开更多
Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett's esophagitis...Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett's esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage Ⅲ or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.展开更多
Objective: Brain Metastasis (BM) from primary gynecologic cancers is a rare entity. The advances and successes in the treatment of primary gynecologic malignancies, have led to prolonged survival and, a higher inciden...Objective: Brain Metastasis (BM) from primary gynecologic cancers is a rare entity. The advances and successes in the treatment of primary gynecologic malignancies, have led to prolonged survival and, a higher incidence of BM. This study aims to report the experience at our institution in managing these patients, and provide possible data points that may be essential to note as prognostic factors, and see if our findings are consistent with the literature in this subject. We also aim to provide a brief literature review of patients with gynecologic cancers and BM. Methods: This is a small single institution retrospective study of 23 patients with a gynecologic malignancy and BM, identified between the years 2007-2015. Data were collected on variables including patient demographics, disease and treatment. Results: The median overall survival from the primary diagnosis was 28 months. Median time from diagnosis of BM to death was 9 months. Conclusion: The outcomes in our study are similar to what is stated in the current literature with regard to BM from gynecologic malignancies. Our literature search also revealed that the molecular analysis and treatment of the primary tumor remain important to prevent BMs. The tendency of tumors to metastasize varies for one tumor type to another for the same type of tumor. The tendency to develop BM may not only depend on risk factors such as stage, grade, and histology, but also on the genetic profile of the primary tumor. The study suggests that multimodal treatment of BM has better outcomes in managing BM from gynecologic cancers.展开更多
Objective:The objectives of this study were to evaluate the long-term results with multimodality therapy, and to clarify the clinicopathologic of features of patients surviving ≥ 3 years for unresectable hepatocellul...Objective:The objectives of this study were to evaluate the long-term results with multimodality therapy, and to clarify the clinicopathologic of features of patients surviving ≥ 3 years for unresectable hepatocellular carcinoma(HCC).Methods:Between 1999 and 2003, a total of 166 patients underwent multimodality therapy for unresectable HCC.All patients underwent multimodality therapy, such as transarterial chemoembolization(TACE), chemotherapy, local ablative therapy, and/ or Chinese traditional medicine.Thirty-nine(23.5%) patients survival ≥ 1 years, and 10(6.0%) patients survived ≥ 3 years.These 39 patients surviving over 1 year were investigated in this study.Eighteen clinical and biologic variables were assessed using univariate and multivariate analyses.Results:TNM staging and tumor extension were isolated by univariate analysis.Only tumor extension was independent risk factors by multiple regression analysis.Of these, 25.6%(10 of 39) survived over 3 years.These 10 patients surviving over 3 years were investigated further.By the end of June 2004, follow-up varied from 3 years and 2 months to 5 years and 1 month.Six patients were still alive with free of disease.Conclusion:Tumor extension was demonstrated to be prognostic of long-term survivors.Multimodality therapy may make a major contribution to achieving long-term survival in patients with unresectable HCC.展开更多
In older patients with comorbidities,hip fractures are both an important and debilitating condition.Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improvin...In older patients with comorbidities,hip fractures are both an important and debilitating condition.Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improving clinical outcomes,the choice of the most effective and safest pathway represents a great challenge.A key point of concern is the anesthetic approach and above all the choice of the locoregional anesthesia combined with general or neuraxial anesthesia.展开更多
Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the bioma...Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression.Here,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer therapy.In this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are packaged.To intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as well.When the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells.These tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation therapy.Overall,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.展开更多
Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic sid...Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects.In the past decade,nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention,high accumulation at tumor sites,co-loading with different drugs,and combination of various therapies.This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy,radiotherapy,phototherapy(photothermal therapy and photodynamic therapy),chemodynamic therapy,gas therapy,and immunotherapy.Additionally,the therapeutic mechanisms,limitations,improvements,and future of the above therapies are discussed.展开更多
BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective....BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective.Poorly differentiated neuroendocrine carcinomas(NECs)represent only 5%-10%of digestive NETS.Due to aggressive growth and rapid metastatic diffusion,early diagnosis and a multidisciplinary approach are mandatory.The role of surgery and radiotherapy in this setting is still debated,and chemotherapy remains the treatment of choice.CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3(Ki67 index>90%)on May 2015 and initially treated with 3 cycles of first-line chemotherapy,but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection.In September 2015,the first post-surgery total-body computed tomography(CT)scan showed an early pelvic disease relapse.Therefore,systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response.This was followed by pelvic radiotherapy(50 Gy).On April 2016,a CT scan and 18F-fluorodeoxy-glucose positron emission tomography imaging showed a complete response(CR)of the pelvic lesion,but pathological abdominal inter-aortocaval lymph nodes were observed.Due to disease progression of abdominal malignant nodes,the patient received radiotherapy at 45 Gy,and finally obtained a CR.As of January 2021,the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.展开更多
The aim of this report was to describe the feasibility, overall survival and quality of life of combining multimodal therapy with a complementary therapy concept called LOTUS Care Cure program. The peritoneal carcinom...The aim of this report was to describe the feasibility, overall survival and quality of life of combining multimodal therapy with a complementary therapy concept called LOTUS Care Cure program. The peritoneal carcinomatosis (PC) working group described their observations on the combination of multimodal therapy with a complementary therapy concept based on 132 patients with different cancer entities with suspected PC. PC was not confirmed by laparoscopy in 32.5% of the patients included in the working group of patients with suspected PC. Patient compliance and the feasibility were high. For Ki67, there is a cut-off at 45% with a slower progression at <45% and a faster progression of the disease at >45%. The higher the Karnofsky index, the more improved the therapy and tolerability, with a cut-off of 80%. Overall, 72.0% of patients died. The median survival time in the overall population was 3.74 years (95% CI, 2.57 to 4.91) with a sharp decline in the first 16 weeks. The quality of life of patients can be improved with the implementation of the complementary LOTUS Care Cure Project. Overall, the therapy of PC requires a multi-professional team of therapists and a multimodal therapy concept. The multimodal concept together with the Lotus Care Cure project shows very good feasibility with high compliance and ultimately leads to better and low-risk patient care.展开更多
Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled ...Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT efficacy.This nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.展开更多
The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge....The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge.Herein,a self-regulated pho-totheranostic nanosystem with single wavelength-triggered photothermal therapy(PTT)/photodynamic therapy(PDT)transformation and oxygen supply for multi-modal synergistic therapy of bacterial biofilm infections is presented.This approach combines a eutectic mixture of natural phase-change materials(PCMs)and an aggregation-induced emission(AIE)phototheranostic agent TPA-ICN to form col-loidally stable nanopartcicles(i.e.AIE@PCM NPs).The reversible solid-liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN,enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs.Addition-ally,oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT.The nanosystem exhibits outstanding therapeu-tic efficacy against bacterial biofilms both in vitro and in vivo,with an antibacterial efficiency of 99.99%.This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release,holding great promise in the safe and efficient treatment of bacterial biofilm infections.展开更多
Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging...Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes (IOMS NCs) via the integration of MoS2 (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a 3?2 relaxivity coefficient of 48.86 (mM)^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.展开更多
Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evi...Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.展开更多
To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract (SE), reduced gra...To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract (SE), reduced graphene oxide (rGO) and gold nanocages (AuNCs). SE conduces to the formation of hydrogel, and also serves as a green material for improving the biocompatibility of hydrogel, and a natural pho- tosensitizer for killing tumor cells under laser radiation (fi60 nm). AuNts show obvious photothermy and can enhance the generation of cytotoxic singlet oxygen (102). The composite hydrogel shell on tumor cells exhibits several competitive advantages including enhanced antitumor effect by retaining the high con- centration of drugs around cancer cell, excellent PDT/FFr compatibility as well as high loading and controllable release of fluorouracil (5-FU) for synergetic multimodal treatment. The survival rate of HeLa cells incubated with 5-FU loaded hydrogel under NIR radiation for 10 min sharply decreases to 1.2%, in- dicating remarkably improved antitumor effects. These results demonstrate that the hydrogel is an excellent delivery carrier for localizable, NIR-responsive and combined PTT/PDT/Chemo synergetic antitumor.展开更多
文摘From 1975 through 1990, 199 patients with limited small cell lung cancer (LSCLC) were subjected to multimodality treatment including surgical resection combined with chemotherapy or chemoradiotherapy in our department. The median postoperative survival time of the 199 patients was 39 months, and the 5-year survival rate was 26%, which was decreased with increase of tumor-stage. In comparison of the survival time of patients in Stage Ⅰ and those in Stage Ⅲa, there was a significant difference (P<0.01). There were no significant differences in survival rate of 3 and 5 years between the patients receiving chemotherapy prior to or after surgical resection. The improvement in survival was documented by surgical resection combined with chemotherapy or chemoradiotherapy for LSCLC. The effect of multimodality treatment is correlated with tumor P-TNM staging, the involvement of lymph node, especially that of the mediastinal lymph node, is a negative factor influencing the prognosis. Surgical resection as an initial management, followed by chemotherapy or chemoradiotherapy may be indicated in LSCLC patients of Stage Ⅰ, Stage Ⅱ and some Stage Ⅲa as the cancer can be resected completely.
文摘Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclu- sively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an e?ort to improve survival. Results from phase III randomized trials are encouraging however, they revealed 五笔字型计算机汉字输入技术 that only patients with major histopathological response will bene?t from treatment. Therefore, predic- tive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym: HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who ful?l the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not bene?t from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-e?ective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.
文摘Spinal cord injury(SCI)is a serious traumatic disease of the central nervous system,which can give rise to the loss of motor and sensory function.Due to its complex pathological mechanism,the treatment of this disease still faces a huge challenge.Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord.Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI.In this review,hydrogel-based multimodal therapeutic strategies to repair SCI are provided,and a combination of hydrogel scaffolds and other therapeutic modalities are discussed,with particular emphasis on the repair mechanism of SCI.
文摘A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.
文摘BACKGROUND Laparoscopic duodenojejunostomy(LDJ) has become the standard surgical procedure for superior mesenteric artery syndrome due to its sufficient outcome in terms of safety and symptom relief. However, there are only a few reports about LDJ for malignant stenosis and its indication remains uncertain.CASE SUMMARY A 77-year-old woman with a history of pancreatic cancer(PC) treated with distal pancreatectomy with en bloc resection of the transverse colon 7 mo ago was admitted for recurrent vomiting. Imaging upon admission revealed marked distention of the duodenum and a tumor around the duodenojejunal flexure. She was diagnosed with malignant stenosis caused by local recurrence of PC. LDJ was performed with an uneventful postoperative course, followed by chemotherapy which gave her 10 mo overall survival.CONCLUSION We think that LDJ is a valuable method for unresectable malignant stenosis around the duodenojejunal flexure as a part of multimodal therapy.
基金supported by the Capital Health Development Research Grant for Youth Scholars (20114002-05)the Funding for Talents Training Project in Beijing (2012D009008000001)
文摘Objective: Combined small cell lung cancer (C-SCLC) is an uncommon subgroup of small cell lung cancer (SCLC) and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.Methods: Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.Results: One hundred and fourteen patients were enrolled, with a median age of 59 (range: 20-79) years old. The most common combined component was squamous cell carcinoma (52.6%). Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients (70.2%) received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival (OS) was 26.2 months. On univariate analysis, smoking (P=0.029), Karnofsky performance score (KPS) 〈80 (P=0.000), advanced TNM stage (P=0.000), no surgery (P=0.010), positive resection margin (P=0.000), positive lymph nodes ≥4 (P=0.000), positive lymph node ratio 〉10% (P=0.000) and non-multimodality treatment (P=0.004) were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉 10% were poor prognostic features. Conclusions: C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉10% are poor prognostic factors.
基金Supported by Medical Science and Technology Project of Henan Province,No.SBGJ2018024。
文摘BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a highly malignant tumour.Hepatectomy is an effective treatment for early ICC,but postoperative recurrence greatly affects patient survival.Studies on recurrent ICC after hepatectomy are lacking.AIM To investigate the clinical characteristics of patients with recurrent ICC after hepatectomy,analyse prognostic factors and explore diagnosis and treatment strategies.METHODS A retrospective analysis was performed on all ICC patients undergoing hepatectomy from January 2013 to August 2021.Patients with postoperative recurrence were selected according to the inclusion and exclusion criteria.Cumulative overall survival was plotted by the Kaplan-Meier method,and differences were assessed by univariate survival analysis using the log-rank test.Multivariate analysis of cumulative survival was performed using the Cox proportional risk model.RESULTS During the 8-year study period,103 patients underwent ICC-related hepatectomy,and 54 exhibited postoperative recurrence.The median disease-free survival(DFS)was 6 mo,the median overall survival(OS)was 9 mo,and the cumulative OS rates at 1,2 and 3 years after the operation were 40.7%,14.8%and 7.4%,respectively.The median OS after recurrence was 4 mo,and the cumulative OS rates at 1,2 and 3 years after recurrence were 16.1%,6.7%and 3.4%,respectively.Multivariate analysis showed that alcohol consumption[hazard ratio(HR)=4.64,95%confidence interval(CI):1.53-14.04,P=0.007]and DFS<6 mo(HR=3.47,95%CI:1.59-7.60,P=0.002)were independent risk factors for the cumulative survival of patients with recurrence,while treatment after recurrence(HR=0.21,95%CI:0.08-0.55,P=0.001)was an independent protective factor.The median OS time of patients receiving multimodality therapy after recurrence of ICC was 7 mo,which was significantly higher than that of patients receiving only local therapy(3 mo),patients receiving systematic therapy(4 mo)and patients receiving the best supportive therapy(1 mo).Patients with recurrent ICC who received multimodality therapy had a significantly better long-term survival after recurrence than those who did not(P=0.026).CONCLUSION The prognosis of patients with recurrence after ICC-related hepatectomy is poor.Alcohol consumption and DFS<6 mo are independent risk factors in terms of the cumulative survival of patients with recurrence,while treatment after recurrence is an independent protective factor.Multimodality therapy can effectively improve the prognosis of patients.
文摘Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett's esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage Ⅲ or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.
文摘Objective: Brain Metastasis (BM) from primary gynecologic cancers is a rare entity. The advances and successes in the treatment of primary gynecologic malignancies, have led to prolonged survival and, a higher incidence of BM. This study aims to report the experience at our institution in managing these patients, and provide possible data points that may be essential to note as prognostic factors, and see if our findings are consistent with the literature in this subject. We also aim to provide a brief literature review of patients with gynecologic cancers and BM. Methods: This is a small single institution retrospective study of 23 patients with a gynecologic malignancy and BM, identified between the years 2007-2015. Data were collected on variables including patient demographics, disease and treatment. Results: The median overall survival from the primary diagnosis was 28 months. Median time from diagnosis of BM to death was 9 months. Conclusion: The outcomes in our study are similar to what is stated in the current literature with regard to BM from gynecologic malignancies. Our literature search also revealed that the molecular analysis and treatment of the primary tumor remain important to prevent BMs. The tendency of tumors to metastasize varies for one tumor type to another for the same type of tumor. The tendency to develop BM may not only depend on risk factors such as stage, grade, and histology, but also on the genetic profile of the primary tumor. The study suggests that multimodal treatment of BM has better outcomes in managing BM from gynecologic cancers.
文摘Objective:The objectives of this study were to evaluate the long-term results with multimodality therapy, and to clarify the clinicopathologic of features of patients surviving ≥ 3 years for unresectable hepatocellular carcinoma(HCC).Methods:Between 1999 and 2003, a total of 166 patients underwent multimodality therapy for unresectable HCC.All patients underwent multimodality therapy, such as transarterial chemoembolization(TACE), chemotherapy, local ablative therapy, and/ or Chinese traditional medicine.Thirty-nine(23.5%) patients survival ≥ 1 years, and 10(6.0%) patients survived ≥ 3 years.These 39 patients surviving over 1 year were investigated in this study.Eighteen clinical and biologic variables were assessed using univariate and multivariate analyses.Results:TNM staging and tumor extension were isolated by univariate analysis.Only tumor extension was independent risk factors by multiple regression analysis.Of these, 25.6%(10 of 39) survived over 3 years.These 10 patients surviving over 3 years were investigated further.By the end of June 2004, follow-up varied from 3 years and 2 months to 5 years and 1 month.Six patients were still alive with free of disease.Conclusion:Tumor extension was demonstrated to be prognostic of long-term survivors.Multimodality therapy may make a major contribution to achieving long-term survival in patients with unresectable HCC.
文摘In older patients with comorbidities,hip fractures are both an important and debilitating condition.Since multimodal and multidisciplinary perioperative strategies can hasten functional recovery after surgery improving clinical outcomes,the choice of the most effective and safest pathway represents a great challenge.A key point of concern is the anesthetic approach and above all the choice of the locoregional anesthesia combined with general or neuraxial anesthesia.
基金financially supported by the National Natural Science Foundation of China(21874066,and 82073288)the National Key R&D Program of China(2019YFA0709200)+5 种基金the Key Research and Development Program of Jiangsu Province(BE2021373,China)Jiangsu Provincial Medical Key Discipline Cultivation Unit(JSDW202239,China)the Natural Science Foundation of Jiangsu Province(BK20200336,China)the Fundamental Research Funds for Central Universities(China)the Program for Innovative Talents and Entrepreneur in Jiangsu(China)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX23_0146,China).
文摘Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression.Here,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer therapy.In this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are packaged.To intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as well.When the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells.These tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation therapy.Overall,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.
基金the Joint Fund Project of National Natural Science Foundation of China,No.U21A20309the National Natural Science Foundation of China,No.22078280,21776238,22006128,22108235 and 22208282.
文摘Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects.In the past decade,nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention,high accumulation at tumor sites,co-loading with different drugs,and combination of various therapies.This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy,radiotherapy,phototherapy(photothermal therapy and photodynamic therapy),chemodynamic therapy,gas therapy,and immunotherapy.Additionally,the therapeutic mechanisms,limitations,improvements,and future of the above therapies are discussed.
文摘BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective.Poorly differentiated neuroendocrine carcinomas(NECs)represent only 5%-10%of digestive NETS.Due to aggressive growth and rapid metastatic diffusion,early diagnosis and a multidisciplinary approach are mandatory.The role of surgery and radiotherapy in this setting is still debated,and chemotherapy remains the treatment of choice.CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3(Ki67 index>90%)on May 2015 and initially treated with 3 cycles of first-line chemotherapy,but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection.In September 2015,the first post-surgery total-body computed tomography(CT)scan showed an early pelvic disease relapse.Therefore,systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response.This was followed by pelvic radiotherapy(50 Gy).On April 2016,a CT scan and 18F-fluorodeoxy-glucose positron emission tomography imaging showed a complete response(CR)of the pelvic lesion,but pathological abdominal inter-aortocaval lymph nodes were observed.Due to disease progression of abdominal malignant nodes,the patient received radiotherapy at 45 Gy,and finally obtained a CR.As of January 2021,the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.
文摘The aim of this report was to describe the feasibility, overall survival and quality of life of combining multimodal therapy with a complementary therapy concept called LOTUS Care Cure program. The peritoneal carcinomatosis (PC) working group described their observations on the combination of multimodal therapy with a complementary therapy concept based on 132 patients with different cancer entities with suspected PC. PC was not confirmed by laparoscopy in 32.5% of the patients included in the working group of patients with suspected PC. Patient compliance and the feasibility were high. For Ki67, there is a cut-off at 45% with a slower progression at <45% and a faster progression of the disease at >45%. The higher the Karnofsky index, the more improved the therapy and tolerability, with a cut-off of 80%. Overall, 72.0% of patients died. The median survival time in the overall population was 3.74 years (95% CI, 2.57 to 4.91) with a sharp decline in the first 16 weeks. The quality of life of patients can be improved with the implementation of the complementary LOTUS Care Cure Project. Overall, the therapy of PC requires a multi-professional team of therapists and a multimodal therapy concept. The multimodal concept together with the Lotus Care Cure project shows very good feasibility with high compliance and ultimately leads to better and low-risk patient care.
基金supported by the National Natural Science Foundation of China(22077030,22271092,21977018,82173657)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX03)。
文摘Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT efficacy.This nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.
基金National Natural Science Foundation of China,Grant/Award Numbers:92163126,52293380,52293383Fundamental Research Funds for the Central Universities,Grant/Award Numbers:63241614,63233051Beijing National Laboratory for Molecular Sciences,Grant/Award Number:BNLMS202308。
文摘The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention.However,efficient eradication of bacterial biofilms remains a challenge.Herein,a self-regulated pho-totheranostic nanosystem with single wavelength-triggered photothermal therapy(PTT)/photodynamic therapy(PDT)transformation and oxygen supply for multi-modal synergistic therapy of bacterial biofilm infections is presented.This approach combines a eutectic mixture of natural phase-change materials(PCMs)and an aggregation-induced emission(AIE)phototheranostic agent TPA-ICN to form col-loidally stable nanopartcicles(i.e.AIE@PCM NPs).The reversible solid-liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN,enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs.Addition-ally,oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT.The nanosystem exhibits outstanding therapeu-tic efficacy against bacterial biofilms both in vitro and in vivo,with an antibacterial efficiency of 99.99%.This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heat-triggered oxygen release,holding great promise in the safe and efficient treatment of bacterial biofilm infections.
基金This study was supported by the National Natural Science Foundation of China (NSFC) (No. 81671829).
文摘Molybdenum disulfide (MoS2), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes (IOMS NCs) via the integration of MoS2 (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a 3?2 relaxivity coefficient of 48.86 (mM)^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.
基金financially supported by the Liaoning Revitalization Talents Program (No. XLYC1907129)the Excellent Youth Science Foundation of Liaoning Province (No. 2020-YQ-06)the China Postdoctoral Science Foundation (No. 2020M670794)。
文摘Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment.
基金supported by the National Natural Science Foundation of China (Nos. 21171001, 51372004, 21571002 and 21371003)the Anhui Province Key Laboratory of Environmentfriendly Polymer Materials+1 种基金the Anhui Provincial College Student Innovation Fund Project (No. 201510375048)Key Project of the Natural Science Foundation of the Provincial Education Department (No. KJ2016A679)
文摘To combine localized drug release with multimodal therapy for malignant tumor, a composite hydrogel as an integrative drug delivery system was facilely prepared. The system contains spinach extract (SE), reduced graphene oxide (rGO) and gold nanocages (AuNCs). SE conduces to the formation of hydrogel, and also serves as a green material for improving the biocompatibility of hydrogel, and a natural pho- tosensitizer for killing tumor cells under laser radiation (fi60 nm). AuNts show obvious photothermy and can enhance the generation of cytotoxic singlet oxygen (102). The composite hydrogel shell on tumor cells exhibits several competitive advantages including enhanced antitumor effect by retaining the high con- centration of drugs around cancer cell, excellent PDT/FFr compatibility as well as high loading and controllable release of fluorouracil (5-FU) for synergetic multimodal treatment. The survival rate of HeLa cells incubated with 5-FU loaded hydrogel under NIR radiation for 10 min sharply decreases to 1.2%, in- dicating remarkably improved antitumor effects. These results demonstrate that the hydrogel is an excellent delivery carrier for localizable, NIR-responsive and combined PTT/PDT/Chemo synergetic antitumor.