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Aqueous zinc-ion hybrid capacitors (ZIHCs), as ideal candidates for high energy-power supply systems, are restricted by unsatisfied energy density and poor cycling durability for further applications. The construction of a surface-functionalized carbon cathode is an effective strategy for improving the performance of ZIHCs. Herein, a high-performance ZIHC is achieved using oxygen-rich hierarchically porous carbon rods (MDPC-X) prepared by the pyrolysis of a metal-organic framework (MOF) assisted by KOH activation. The MDPC-X samples displayed high electric double-layer capacitance (EDLC) and pseudocapacitance owing to their oxygen-rich surfaces, abundant electroactive sites, and short ions/electron transfer lengths. The surface oxygen functional groups for the reversible chemical adsorption/desorption of Zn2+ are identified using ex situ X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Consequently, the as-assembled ZIHC exhibited a high capacity of 323.4 F g-1 (161.7 mA h g-1) at 0.5 A g-1 and a retention of 147 F g-1 (73.5 mA h g-1) at an ultrahigh current density of 50 A g-1, corresponding to high energy and power densities of 145.5 W h kg-1 and 45 kW kg-1, respectively. Furthermore, an excellent cycling life with 96.5% of capacity retention is also maintained after 10 000 cycles at 10 A g-1, demonstrating its promising potential for applications.
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As a promising low-cost and high-safety energy storage candidate, zinc-ion hybrid capacitors (ZIHCs) have received extensive attention. For maximizing the advantages of ZIHC with high energy density and high power density, the structural engineering of the porous carbon materials is the crucial and effective strategy. Herein, an oxygen-enriched hierarchical porous carbon has been fabricated from the pyrolysis of olive leaves combing the chemical activation. The abundant interfacial active sites and short ions/electrons transfer length endow the hierarchical porous carbon cathode with high ions adsorption capacity and fast kinetic behaviors. Meanwhile, the oxygen-rich functional groups can provide extra pseudocapacitance and improve the wettability and conductivity of porous carbon. Benefiting from these advantages, an anti-self-discharge ZIHC device with a high energy-power feature has been assembled. The electrochemical process is studied by ex situ X-ray diffraction (XRD) and scanning electron microscope (SEM) methods. Finally, an excellent energy density of 136.3 W h kg-1 , and high power output of 20 kW kg-1 , as well as long cycle life with 91% capacity retention over 20â¯000 cycles at 10 A g-1 are realized by as-assembled ZIHC.
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OBJECTIVE: Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM. METHODS: This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias. RESULTS: Of 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58-0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%-14.8%) and 18.4% (95% CI, 12.3%-24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months. CONCLUSIONS: Compared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.
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BACKGROUND: Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown. METHODS: LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments. RESULTS: LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/ß-catenin pathway in an APC-dependent manner. CONCLUSIONS: Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/ß-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.
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Proteína da Polipose Adenomatosa do Colo/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , Proteína da Polipose Adenomatosa do Colo/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Metástase Neoplásica , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
BACKGROUND/AIMS: Considerable evidence indicates that long noncoding RNAs (lncRNAs) exert importantly regulatory functions during human cancer initiation and progression and are promising biotargets in the flight against cancer. METHODS: In this study, we evaluated the role of the lncRNA LINC01133 in esophageal squamous cell carcinoma (ESCC). LINC01133 expression in ESCC was examined by quantitative real-time PCR. The correlations between LINC01133 expression and clinicopathological variables and survival were examined by the χ2 test, Kaplan-Meier method, log-rank test, and univariate Cox regression analysis. RESULTS: LINC01133 expression levels were frequently lower in ESCC tissues and cell lines than in paired normal tissues and an immortalized esophageal epithelial cell line, respectively. The expression of LINC01133 decreased in a TNM stage- and lifestyle-independent manner. LINC01133 was an independent protective factor and had an anti-tumor effect in the early stage of ESCC development. More importantly, we discovered that drinking status in our cohort impaired the predictive accuracy of LINC01133 for patients with ESCC. Furthermore, a new risk model combining LINC01133 expression, drinking status, and TNM stage provided better survival discrimination compared with three other predictors. CONCLUSIONS: Our data indicate that a loss of LINC01133 expression is a potential poor prognostic biomarker and therapeutic target for ESCC and provide additional prognostic information to improve the outcomes of ESCC patients.
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Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , RNA Longo não Codificante/metabolismo , Consumo de Bebidas Alcoólicas , Área Sob a Curva , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , Curva ROCRESUMO
BACKGROUND/AIMS: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells. METHODS: The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial-mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot. RESULTS: XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells. CONCLUSION: High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.
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Resistencia a Medicamentos Antineoplásicos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/metabolismo , Resistência a Múltiplos Medicamentos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Regulação para CimaRESUMO
Materials and Methods: Hsa_circ_0051908 expression was determined using RT-qPCR. HCC cell proliferation, apoptosis, invasion, and migration were assessed using CCK-8 assay, EdU staining, TUNEL staining, flow cytometry, and transwell assay. The molecular mechanism was analyzed using western blotting. In addition, the role of hsa_circ_0051908 in tumor growth was evaluated in vivo. Results: Hsa_circ_0051908 expression was increased in both HCC tissues and cell lines. The proliferation, migration, and invasion of HCC cells were significantly decreased after hsa_circ_0051908 knockdown, while cell apoptosis was notably increased. Furthermore, we found that hsa_circ_0051908 silencing downregulated vimentin and Snail and upregulated E-cadherin. In vivo, hsa_circ_0051908 silencing significantly inhibited the growth of the tumor. Conclusions: Our data provide evidence that hsa_circ_0051908 promotes HCC progression partially by mediating the epithelial-mesenchymal transition process, and it may be used for HCC treatment.
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Carcinoma Hepatocelular , Progressão da Doença , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , RNA Circular , Animais , Humanos , Masculino , Apoptose/genética , Caderinas/metabolismo , Caderinas/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , RNA Circular/genética , RNA Circular/metabolismo , Vimentina/metabolismo , Vimentina/genéticaRESUMO
Background: Hsa_circ_0028861, a newly discovered serum exosome circular RNA (circRNA), is greatly reduced in the serum of patients with hepatocellular carcinoma (HCC). However, the exact role of hsa_circ_0028861 in the progression of liver cancer is still unknown. Materials and Methods: Thirty patients with HCC were enrolled in this study. Hsa_circ_0028861 expression was explored via real-time polymerase chain reaction (PCR) assay. The influence of curcumol on HCC cells were tested using CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, cell wound healing assay, and migration assay, respectively. The related mechanism was determined by Western blot. A xenograft tumor model was constructed, and mice were administrated with curcumol. Results: The expression of hsa_circ_0028861 in tumor tissues was elevated of patients with HCC and in HCC cells. Curcumol treatment decreased the expression of hsa_circ_0028861 in HCC cells. Curcumol treatment could largely suppress the viability, proliferation, and migration of HCC cells by reducing hsa_circ_0028861 expression and mediating the epithelial-mesenchymal transition (EMT) process. Curcumol also effectively restrained tumor growth in the HCC mice model. Conclusions: Curcumol exerted an inhibitory role in HCC progression by downregulating hsa_circ_0028861 expression and mediating the EMT process, which provides evidence for screening new therapeutic targets and drug therapies for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Sesquiterpenos , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , MicroRNAs/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Gastric cancer (GC) is a malignant tumor with seriously poor outcomes. Studies have shown that microRNAs (miRNAs) play an omnifarious regulatory effect in GC. However, the role of miR-3650 in the progression of GC is not well known. METHODS: In this study, miR-3650 expression and its clinical significance were determined using clinical specimens. The biological functions of miR-3650 were determined in gastric cancer cell lines through CCK-8, cell scratch, and transwell experiments. Bioinformatics predictions, combined with Western blot experiments, were employed to explore its downstream molecular targets. RESULTS: We observed that miR-3650 was overexpressed in GC specimens and most cell lines, i.e., 77.8% (MKN28, SNU1, AGS, MKN45, N87, BGC823 and SGC7901). The overexpression correlated with advanced T-stage, N-stage, M-stage, and TNM-stage. Furthermore, miR-3650 promoted the proliferation and migration of gastric cancer cells, and its overexpression promoted the PI3K-AKT-mTOR pathway and inhibited the PTEN and hippo pathways. The potassium ion signaling pathway was also involved in the biological process of miR-3650 promoting cancer. CONCLUSION: Therefore, we concluded that miR-3650/PTEN/PI3K-AKT-mTOR and miR-3650/hippo pathways are vital in the progression of GC and serve as novel targets for GC therapy.
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MicroRNAs , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Gastric cancer (GC) is one of the most common malignant tumors globally. About 20-30% of patients with gastric cancer show peritoneal implantation metastasis at the first diagnosis. Peritoneal metastasis is responsible for 70% of deaths of patients with advanced gastric cancer. Although there are many ways to treat advanced gastric cancer, the prognosis of patients with recurrence is unsatisfactory. An auxiliary treatment with hyperthermic intraperitoneal chemotherapy (HIPEC), is an internationally recognized recommended treatment for advanced gastric cancer. A series of clinical trials have shown that HIPEC significantly improves the overall survival of patients with cancer. Compared with the cytoreductive surgery (CRS) alone, HIPEC combined with CRS markedly reduced the rate of peritoneal metastasis in patients with ovarian cancer and colorectal cancer. It has been demonstrated that HIPEC alters transcription of many genes by affecting non-coding RNAs, which may contribute to the suppressive effect of HIPEC on the synthesis of nucleic acids and proteins in cancer cells. This paper reviews the recent advances in understanding the role of non-coding RNAs in tumor invasion and metastasis of advanced gastric cancer. We also consider changes in noncoding RNA levels and other molecules in advanced gastric cancer cases treated with HIPEC. We hope that our review will provide a reference for future research on molecular epidemiology and etiology of advanced gastric cancer and promote precise treatment of this malignancy using HIPEC.
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Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , RNA Neoplásico , RNA não Traduzido , Neoplasias Gástricas , Humanos , RNA Neoplásico/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
Background: Gastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC. Methods: Biomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study. Results: The tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan-Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts. Conclusion: We found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.
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Nasopharyngeal carcinoma (NPC) is characterised by distinct geographical distribution and is particularly prevalent in Asian countries. But the mechanisms related to the progression of nasopharyngeal carcinoma (NPC) are not completely understood. MiR-124-3p functions as a tumor suppressor in many kinds of human cancers. Here, we explored the effects and mechanism of miR-124-3p on the proliferation and colony formation in NPC. In our study, we reported that miR-124-3p was significantly downregulated in NPC tissues and cell lines. Overexpression miR-124-3p decreased NPC cell proliferation and colony formation abilities. Meanwhile, knockdown miR-124-3p increased proliferation and colony formation abilities. Additionally, dual-luciferase assay showed that miR-124-3p could positively regulated PCDH8 by targeting its 3'-UTR. Overexpression of PCDH8 could partially rescue the proliferation and colony formation role of miR-124-3p inhibitor. Our study indicated that miR-124-3p played a tumor suppressor by directly interacting with PCDH8 and inhibiting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Overall, we found that miR-124-3p inhibited the activation of the PI3K/AKT/mTOR signaling pathway in NPC by interacting with PCDH8. Thus, PCDH8 may be a potential molecular target that impeded NPC proliferation and colony formation.
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Current administrations for precision drug uses are limited in evaluation speed. Here, we propose the use of multiplex gene-based digital markers for the extremely rapid personalized prediction of individual sensitivity to cancer drugs. We first screen the transcriptional profiles by applying two to three gene filters and scoring genes by their impact on drug sensitivity and finalize the gene lists by K-nearest neighbors cross-validation. The digital markers are cancer type dependent, are composed of tens to hundreds of gene expressions, and are rapidly quantified by reverse transcription quantitative real-time PCR (qRT-PCR) within 1-3 h after tumor sampling. The area under the receiver operating characteristic curve reached 0.88 when testing the performance of digital markers on organoids derived from colorectal cancer patient tumors. The algorithm and corresponding graphic user interface were developed to demonstrate the promise of digital markers for extremely rapid drug recommendation.
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Objective: To compare the efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) and intravesical chemotherapy (IVEC) in patients with intermediate and high risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection. Methods: We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers. We matched 364 intermediate or high risk cases and divided them into 2 groups: the HIVEC+IVEC group [chemohyperthermia (CHT) composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia] and the IVEC group (intravesical instillation without hyperthermia). The data were recorded in the database. The primary endpoint was 2-year recurrence-free survival (RFS) in all NMIBC patients (n = 364), whereas the secondary endpoints were the assessment of radical cystectomy (RC) and 5-year overall survival (OS). Results: There was a significant difference in the 2-year RFS between the two groups in all patients (n = 364; HIVEC+IVEC: 82.42% vs. IVEC: 74.18%, P = 0.038). Compared with the IVEC group, the HIVEC+IVEC group had a lower incidence of RC (P = 0.0274). However, the 5-year OS was the same between the 2 groups (P = 0.1434). Adverse events (AEs) occurred in 32.7% of all patients, but none of the events was serious (grades 3-4). No difference in the incidence or severity of AEs between each treatment modality was observed. Conclusions: This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients. Both treatments were well-tolerated in a similar manner.
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Antineoplásicos/uso terapêutico , Cistectomia , Hipertermia Induzida , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , China/epidemiologia , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
OBJECTIVE: Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer. Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia; validate an index of the hyperthermia chemotherapy sensitization enhancement ratio (HCSER) to identify the chemotherapeutics most enhanced by hyperthermia; and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment. METHODS: Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines. Cells from both sources were encapsulated in 3D Matrigel droplets, which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres. The microspheres were seeded in 96-well plates, with each well containing a single microsphere that developed into an organoid after 7 days. The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37°C as a control and 43°C for 90 min to examine hyperthermia synergism. Cell viability was counted with 10% CCK8. RESULTS: We successfully established a library of colorectal cancer organoids from 22 patient parental tumors. We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs. In 11 of the 22 patient organoids, raltitrexed had significant hyperthermia synergism, which was indexed as the highest HCSER score within each patient group. CONCLUSIONS: Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics. We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs.
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Importance: Interval cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising oncologic outcomes for patients with advanced ovarian cancer, but a large-scale, multicenter study to evaluate the efficacy of HIPEC combined with primary cytoreductive surgery (PCS) has yet to be conducted. Objective: To compare survival outcomes between PCS with HIPEC vs PCS alone for patients with stage III epithelial ovarian cancer. Design, Setting, and Participants: This cohort study was conducted from January 2010 to May 2017 at 5 high-volume institutions in China. A total of 584 patients with stage III primary epithelial ovarian cancer were treated with either PCS alone or PCS with HIPEC. The median (interquartile range) follow-up period was 42.2 (33.3-51.0) months. Data analysis was conducted from August to December 2019. Exposures: PCS with HIPEC vs PCS alone. Main Outcomes and Measures: Primary outcomes were median survival time and 3-year overall survival. The inverse probability of treatment weighting (IPTW) method, based on propensity score, was used to control for confounding factors. Results: From a total of 789 patients with stage III epithelial ovarian cancer, 584 patients (74.0%; mean [SD] age, 55.0 [10.5] years) were ultimately included for IPTW in this study. Of the 584 patients, 425 (72.8%) underwent PCS with HIPEC and 159 (27.2%) underwent PCS alone. After IPTW adjustment, the median survival time was 49.8 (95% CI, 45.2-60.2) months for patients undergoing PCS with HIPEC and 34.0 (95% CI, 28.9-41.5) months for patients undergoing PCS alone, and the 3-year overall survival rate was 60.3% (95% CI, 55.3%-65.0%) for patients undergoing PCS with HIPEC and 49.5% (95% CI, 41.0%-57.4%) for patients undergoing PCS alone (weighted hazard ratio, 0.64; 95% CI, 0.50-0.82; P < .001). Further stratified into complete and incomplete surgery subgroups, patients in the PCS with HIPEC group had significantly better survival than those in the PCS group, except for the 3-year overall survival rate in the incomplete subgroup. Among those who underwent complete surgical procedures and comparing those who received PCS with HIPEC vs those who received PCS alone, the median survival time was 53.9 (95% CI, 46.6-63.7) months vs 42.3 (95% CI, 31.1-59.3) months (P = .02), and the 3-year overall survival rate was 65.9% (95% CI, 60.1%-71.2%) vs 55.4% (95% CI, 44.7%-64.8%) (P = .04); meanwhile, among patients who underwent incomplete surgical procedures and comparing those who received PCS with HIPEC vs those who received PCS alone, the median survival time was 29.2 (95% CI, 22.3-45.5) months vs 19.9 (95% CI, 11.6-39.1) months (P = .03), and the 3-year OS rate was 44.3% (95% CI, 34.6%-53.4%) vs 36.7% (95% CI, 23.4%-50.1%) (P = .19). The treatment was well tolerated in both groups. Conclusions and Relevance: In this study, the PCS with HIPEC treatment approach was associated with better long-term survival. When complete PCS is possible, this approach could be a valuable therapy for patients with stage III epithelial ovarian cancer.