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1.
Clin Transl Oncol ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472748

RESUMO

BACKGROUNDS: 125I brachytherapy is effective in relieving cancer pain due to osteolytic bone metastases. However, fewer studies focused on painful osteoblastic bone metastases (OBMs), we conducted a retrospective study to evaluate the efficacy of 125I brachytherapy for the treatment of painful OBMs. METHODS: From April 2017 to April 2019, clinical data of a total of 65 patients with OBMs who underwent CT/cone beam CT -guided 125I brachytherapy were collected and analyzed. The primary study endpoints were technical success, relief of pain (RoP), and quality of life (QoL). The secondary study endpoints were treatment-related complications, local tumor control (LCR), and overall survival (OS). The logistic regression analysis was performed to predict RoP. RESULTS: Technical success rate was 100%. Visual analog scale scores and daily morphine consumption continuously decreased significantly at 2 weeks, 6 weeks, and 10 weeks (all P < 0.05). The RoP at 6 weeks was 84.62%. QoL presented improvement at 6 and 10 weeks. Only minor complications occurred in 12 patients (18.46%). LCR was 93.85% at 10 weeks. The OS was 29.80 months. Two factors were significantly associated with the RoP: max diameter (MD, < 3 cm vs. ≥ 3 cm, P = 0.019) and serum levels of bone alkaline phosphatase (B-ALP, ≥ 100 U/L vs. < 100 U/L, P = 0.016). CONCLUSIONS: 125I brachytherapy is an effective treatment in relieving painful OBMs and improving patients' QoL.

2.
Clin Res Hepatol Gastroenterol ; : 102060, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36473631

RESUMO

OBJECTIVE: Camrelizumab synergizes with apatinib or transarterial chemoembolization via tumor immunity and chemosensitivity. This study aimed to investigate the efficacy and safety of camrelizumab plus apatinib with or without drug-eluting bead transarterial chemoembolization (DEB-TACE) in unresectable hepatocellular carcinoma (HCC) patients after progression to DEB-TACE plus apatinib. METHODS: Eighty-nine unresectable HCC patients accepted previous DEB-TACE plus apatinib therapy, then further received second-line camrelizumab plus apatinib with or without DEB-TACE treatment. Treatment responses were calculated at 3 months (M3) and 6 months (M6). Survival and treatment-related adverse events were documented. RESULTS: Objective response rate and disease control rate were 39.3% and 80.9% at M3; meanwhile, they were 22.4% and 54.1% at M6. Furthermore, the median progression-free survival (PFS) (95% confidence interval (CI)) was 7.0 (6.2-7.8) months with a 1-year PFS rate of 18.4%; the median overall survival (OS) (95% CI) was 17.0 (15.3-18.7) months with a 1-year OS rate of 73.9%. Multivariable Cox's proportional hazards regression analysis presented that 3-4 times (vs. 0 time) of DEB-TACE, apatinib dose duration> 4 months, and camrelizumab dose duration> 5 months independently predicted longer PFS (all P<0.05); meanwhile, declined ECOG PS score, new lesions as progression pattern, 1-2 and 3-4 times (vs. 0 time) of DEB-TACE, apatinib dose duration> 4 months independently predicted prolonged OS (all P<0.05). Moreover, treatment-related adverse events mainly included grade 1-2 fever, gastrointestinal reaction, fatigue, hand-foot skin reaction, and hypertension. CONCLUSION: After progression to DEB-TACE plus apatinib treatment, the addition of camrelizumab is effective and safe among unresectable HCC patients.

4.
Front Pharmacol ; 13: 1079707, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518678

RESUMO

Aim: Drug-eluting beads are usually applied for the treatment of advanced hepatocellular carcinoma. Oxaliplatin was suggested as first-line therapy for advanced non-small-cell lung cancer. However, there has been little investigation about the application of drug-eluting beads transarterial chemoembolization (DEB-TACE) with oxaliplatin-loaded CalliSpheres beads (CB) for the treatment of unresectable or advanced lung cancer. We aimed to investigate the safety and efficacy of oxaliplatin-loaded DEB-TACE for the treatment of unresectable or advanced lung cancer. Methods: From January 2019 to December 2021, all patients with primary unresectable or advanced lung cancer who underwent DEB-TACE with oxaliplatin-loaded CB were retrospectively enrolled. This study defined overall survival and objective response rate (ORR) as the primary endpoints, disease control rate (DCR) and progression-free survival (PFS) as the secondary endpoints. Results: A total of 33 sessions of DEB-TACE were performed in 20 patients, with a mean of 1.7 ± 1.0 sessions. A total of 55 arteries were emoblized by CB, including 40 bronchial arteries, 13 intercostal arteries, one suprarenal artery and one inferior phrenical artery. No procedural-related mortality or severe complications were observed. The median tumor diameter was 49.0 [Interquartile range (IQR) 37.8-66.8] mm before DEB-TACE, and decreased to 38.8 (IQR 27.7-56.9), 26.1 (IQR 19.1-48.8), and 20.5 (IQR 13.1-49.7) mm at 1, 3 and 6 months later (p = 0.04). The ORR and DCR at 1, 3, and 6 months after DEB-TACE were 28.6% and 92.9%, 38.5% and 84.6%, 30.8% and 61.5%, respectively. The median PFS and median overall survival was 9.9 and 29.6 months, respectively. Conclusion: DEB-TACE with oxaliplatin-loaded CB is suggested as a safe, effective and well-tolerated treatment for patients with unresectable or advanced lung cancer.

5.
J Hepatocell Carcinoma ; 9: 1341-1352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36575732

RESUMO

Purpose: Chemoresistance is a major factor contributing to the failure of cancer treatment. The conventional chemotherapy agent 5-fluorouracil (5-FU) has been used for cancer treatment for decades. However, its use is limited in the treatment of hepatocellular carcinoma (HCC) due to acquired resistance. Nrf2 (NF-E2-related factor 2) is known to be associated with drug resistance across a wide range of cancer types. Also, since arsenic trioxide (As2O3) showed antitumor effects on HCC, the purpose of this study was to determine whether As2O3 and Nrf2-siRNA could inhibit HCC synergistically. Methods: We generated two separate 5-FU-resistant HCC cell lines (SNU-387/5-FU and Hep3B/5-FU). Western blotting was used to determine protein levels. An efficient lentiviral delivery system was used to establish stable knockdown or overexpression of Nrf2 and HIF-1α. In vitro and in vivo analyses of the effects of Nrf2 gene knockdown and As2O3 on 5-FU-resistant HCC cells were conducted. Results: The expression of Nrf2 was higher in the 5-FU-resistant HCC cell lines than in the parental cell lines. When coupled with Nrf2 knockdown, As2O3 treatment significantly decreased 5-FU-resistant SNU-387 and Hep3B cell viability, migration, and invasion, inactivated HIF-1α/HSP70 signaling, inhibited anti-apoptotic B-cell lymphoma (Bcl-2) activity, and increased the expression of pro-apoptotic Bcl-2-associated X protein (BAX) along with caspase-3. The synergistic effect was also confirmed using a 5-FU-resistant Hep3B mouse xenograft model in vivo. Conclusion: Nrf2 knockdown could improve the effect of As2O3 on reversing drug resistance in 5-FU-resistant HCC cells.

7.
Mol Cancer ; 21(1): 220, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517820

RESUMO

Cancer drug resistance represents the main obstacle in cancer treatment. Drug-resistant cancers exhibit complex molecular mechanisms to hit back therapy under pharmacological pressure. As a reversible epigenetic modification, N6-methyladenosine (m6A) RNA modification was regarded to be the most common epigenetic RNA modification. RNA methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) are frequently disordered in several tumors, thus regulating the expression of oncoproteins, enhancing tumorigenesis, cancer proliferation, development, and metastasis. The review elucidated the underlying role of m6A in therapy resistance. Alteration of the m6A modification affected drug efficacy by restructuring multidrug efflux transporters, drug-metabolizing enzymes, and anticancer drug targets. Furthermore, the variation resulted in resistance by regulating DNA damage repair, downstream adaptive response (apoptosis, autophagy, and oncogenic bypass signaling), cell stemness, tumor immune microenvironment, and exosomal non-coding RNA. It is highlighted that several small molecules targeting m6A regulators have shown significant potential for overcoming drug resistance in different cancer categories. Further inhibitors and activators of RNA m6A-modified proteins are expected to provide novel anticancer drugs, delivering the therapeutic potential for addressing the challenge of resistance in clinical resistance.


Assuntos
Adenosina , Neoplasias , Humanos , Adenosina/metabolismo , Metiltransferases/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , RNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Microambiente Tumoral
9.
Elife ; 112022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36345721

RESUMO

Molecular subtypes of colorectal cancer (CRC) are currently identified via the snapshot transcriptional profiles, largely ignoring the dynamic changes of gene expressions. Conversely, biological networks remain relatively stable irrespective of time and condition. Here, we introduce an individual-specific gene interaction perturbation network-based (GIN) approach and identify six GIN subtypes (GINS1-6) with distinguishing features: (i) GINS1 (proliferative, 24%~34%), elevated proliferative activity, high tumor purity, immune-desert, PIK3CA mutations, and immunotherapeutic resistance; (ii) GINS2 (stromal-rich, 14%~22%), abundant fibroblasts, immune-suppressed, stem-cell-like, SMAD4 mutations, unfavorable prognosis, high potential of recurrence and metastasis, immunotherapeutic resistance, and sensitive to fluorouracil-based chemotherapy; (iii) GINS3 (KRAS-inactivated, 13%~20%), high tumor purity, immune-desert, activation of EGFR and ephrin receptors, chromosomal instability (CIN), fewer KRAS mutations, SMOC1 methylation, immunotherapeutic resistance, and sensitive to cetuximab and bevacizumab; (iv) GINS4 (mixed, 10%~19%), moderate level of stromal and immune activities, transit-amplifying-like, and TMEM106A methylation; (v) GINS5 (immune-activated, 12%~24%), stronger immune activation, plentiful tumor mutation and neoantigen burden, microsatellite instability and high CpG island methylator phenotype, BRAF mutations, favorable prognosis, and sensitive to immunotherapy and PARP inhibitors; (vi) GINS6, (metabolic, 5%~8%), accumulated fatty acids, enterocyte-like, and BMP activity. Overall, the novel high-resolution taxonomy derived from an interactome perspective could facilitate more effective management of CRC patients.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Humanos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Ilhas de CpG , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Metilação de DNA , Instabilidade de Microssatélites , Mutação , Proteínas Cromossômicas não Histona/metabolismo
10.
Cell Death Dis ; 13(11): 925, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335094

RESUMO

The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.


Assuntos
Ferroptose , Neoplasias , Humanos , Necrose , Neoplasias/metabolismo , Ferro/metabolismo , Tolerância Imunológica , Microambiente Tumoral
11.
Cell Mol Life Sci ; 79(11): 577, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316529

RESUMO

Recently, immunotherapy has gained increasing popularity in oncology. Several immunotherapies obtained remarkable clinical effects, but the efficacy varied, and only subsets of cancer patients benefited. Breaking the constraints and improving immunotherapy efficacy is extremely important in precision medicine. Whereas traditional sequencing approaches mask the characteristics of individual cells, single-cell sequencing provides multiple dimensions of cellular characterization at the single-cell level, including genomic, transcriptomic, epigenomic, proteomic, and multi-omics. Hence, the complexity of the tumor microenvironment, the universality of tumor heterogeneity, cell composition and cell-cell interactions, cell lineage tracking, and tumor drug resistance mechanisms are revealed in-depth. However, the clinical transformation of single-cell technology is not to the point of in-depth study, especially in the application of immunotherapy. The newly discovered vital cells and tremendous biomarkers facilitate the development of more efficient individualized therapeutic regimens to guide clinical treatment and predict prognosis. This review provided an overview of the progress in distinct single-cell sequencing methods and emerging strategies. For perspective, the expanding utility of combining single-cell sequencing and other technologies was discussed.


Assuntos
Neoplasias , Proteômica , Humanos , Imunoterapia/métodos , Microambiente Tumoral/genética , Medicina de Precisão/métodos , Neoplasias/genética , Neoplasias/terapia , Biomarcadores Tumorais , Análise de Célula Única
12.
Quant Imaging Med Surg ; 12(10): 4837-4851, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36185058

RESUMO

Background: Microwave ablation (MWA) for hepatocellular carcinoma (HCC) under the hepatic dome is still clinically challenging. This retrospective control study set out to analyze the technical application and clinical benefits of cone beam computed tomography (CBCT)-guided MWA for HCC under the hepatic dome. Methods: The study analyzed 76 patients with 110 HCC lesions under the hepatic dome from April 2016 to January 2020. The patients were divided into two groups: (I) the CBCT group (n=31), in which iGuide navigation was used for the puncture, and (II) the conventional computed tomography (cCT) group (n=45), in which a navigation tool was not used for the puncture. The primary endpoints were technical success, puncture score, and the rates of complete ablation (CA), complications, and local tumor progression (LTP). The secondary endpoints were tumor-free survival (TFS) and overall survival (OS). Results: In terms of the primary endpoints, the puncture score, occurrence of pleural effusion, and occurrence of right shoulder pain differed significantly between the CBCT group and the cCT group (2.8 vs. 2.2, P=0.002; 12.9% vs. 35.6%, P=0.03; 9.7% vs. 33.3%, P=0.03, respectively). However, the rates of technical success, CA, major complications, and LTP showed no significant differences between the two groups (100% vs. 100%, P>0.009; 0% vs. 0%, P>0.009; 95.6% vs. 89.2%, P=0.30; 4.5% vs. 4.6%, P=0.96, respectively). Regarding the secondary endpoints, the median TFS was 23.0 [95% confidence interval (CI): 19.5-26.5] vs. 22.0 (95% CI: 18.4-25.6) months (P=0.41) and the median OS was 31.0 (95% CI: 21.4-40.6) vs. 33.0 (95% CI: 27.9-38.2) months (P=0.95). Conclusions: Cone beam CT is a feasible and effective image guidance tool for MWA of HCC under the hepatic dome.

13.
Elife ; 112022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36282174

RESUMO

As the most aggressive tumor, the outcome of pancreatic cancer (PACA) has not improved observably over the last decade. Anatomy-based TNM staging does not exactly identify treatment-sensitive patients, and an ideal biomarker is urgently needed for precision medicine. Based on expression files of 1280 patients from 10 multicenter cohorts, we screened 32 consensus prognostic genes. Ten machine-learning algorithms were transformed into 76 combinations, of which we selected the optimal algorithm to construct an artificial intelligence-derived prognostic signature (AIDPS) according to the average C-index in the nine testing cohorts. The results of the training cohort, nine testing cohorts, Meta-Cohort, and three external validation cohorts (290 patients) consistently indicated that AIDPS could accurately predict the prognosis of PACA. After incorporating several vital clinicopathological features and 86 published signatures, AIDPS exhibited robust and dramatically superior predictive capability. Moreover, in other prevalent digestive system tumors, the nine-gene AIDPS could still accurately stratify the prognosis. Of note, our AIDPS had important clinical implications for PACA, and patients with low AIDPS owned a dismal prognosis, higher genomic alterations, and denser immune cell infiltrates as well as were more sensitive to immunotherapy. Meanwhile, the high AIDPS group possessed observably prolonged survival, and panobinostat may be a potential agent for patients with high AIDPS. Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment of PACA.


Assuntos
Perfilação da Expressão Gênica , Neoplasias Pancreáticas , Humanos , Perfilação da Expressão Gênica/métodos , Consenso , Inteligência Artificial , Panobinostat , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Aprendizado de Máquina , Biomarcadores
14.
Urol Oncol ; 40(12): 537.e11-537.e17, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36216664

RESUMO

BACKGROUND: Long-term conventional high-dose radiation therapy can lead to retroperitoneal fibrosis and nerve damage in patients with advanced ureteral carcinoma (UC). The purpose of this study is to evaluate the safety and efficacy of nephrostomy combined with iodine-125 seed strand (ISS) brachytherapy for the treatment of UC. MATERIALS AND METHODS: Twenty-one patients with UC were treated with nephrostomy combined with ISS brachytherapy. The following parameters were recorded: technical success rate, procedure time, complications, mean D90 (dose delivered to the 90% gross tumor volume), organ at risk (OAR) dose, local control rate (LCR), ureteral patency (UP), local tumor progression (LTP), and overall survival (OS). The hydronephrosis score (HS), visual analog score (VAS), Karnofsky score and maximum diameter (MD) were compared before and 8 weeks after the operation. RESULTS: The technical success rate was 100%, with a mean procedure time of 54.6 min. Three cases (14.5%) had bladder implant metastasis but no other major complications, such as ureteral perforation, infection, or severe bleeding, occurred. The mean D90 and OAR doses were 50.7 and 3.8 Gy, respectively. LCR was 100% with 28.6% UP at the 8-week evaluation. During the mean follow-up of 16.6 months, LTP occurred in 4 cases (19.1%), and the median OS was 25.0 months (95% CI 21.3-28.5). The HS, VAS, Karnofsky score and MD showed significant changes (all P < 0.01). CONCLUSION: UC can be safely and effectively treated by nephrostomy combined with ISS brachytherapy, a viable option for patients who cannot undergo or refuse surgical resection.


Assuntos
Braquiterapia , Carcinoma , Humanos , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Radioisótopos do Iodo/uso terapêutico , Carcinoma/tratamento farmacológico , Bexiga Urinária , Dosagem Radioterapêutica , Resultado do Tratamento
15.
J Transl Med ; 20(1): 463, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221084

RESUMO

BACKGROUND: Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. METHODS: Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-ß and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. RESULTS: Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). CONCLUSIONS: In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.


Assuntos
Embolização Terapêutica , Lidocaína , Carragenina , Hemólise , Humanos , Inflamação , Interleucina-10 , Interleucina-6 , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Fator de Crescimento Transformador beta
16.
Sci Rep ; 12(1): 17215, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36241689

RESUMO

To investigate the safety and effectiveness of trans-oral trans-sheath forceps biopsy (TTFB) for patients with severe esophageal obstruction under fluoroscopy. From November 2016 to November 2019, 35 patients with level III or IV dysphagia and a Karnofsky score of less than 60 were enrolled to undergo TTFB and esophageal nutrition tube insertion or stenting simultaneously. Data on diagnostic performance, early complications, and radiation dose were collected, and Karnofsky scores before and after the procedures were compared. The technical success of TTFB was 100%. The sensitivity, specificity and accuracy were 92.3% (24/26), 77.8% (7/9), and 88.6% (31/35), respectively. Complications occurred in two cases (5.7%). The mean procedure duration and irradiation dose were 23.2 min and 7.2 mSv, respectively. The Karnofsky scores significantly increased after 2-4 weeks (t = 11.22, P < 0.0001). TTFB is a safe and effective method for patients with severe esophageal obstruction under fluoroscopy, especially in those who cannot undergo or refuse endoscopy.


Assuntos
Neoplasias Esofágicas , Estenose Esofágica , Biópsia/efeitos adversos , Neoplasias Esofágicas/complicações , Estenose Esofágica/complicações , Fluoroscopia/métodos , Humanos , Estudos Retrospectivos , Instrumentos Cirúrgicos/efeitos adversos
17.
Medicine (Baltimore) ; 101(39): e30894, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181045

RESUMO

To determine the safety, feasibility and clinical outcomes of interventional methods for the management of esophagomediastinal fistula, and to investigate the effect of stent placement on fistula healing and the swallowing. Sixty consecutive patients with esophagomediastinal fistula were treated using interventional method and were retrospectively assessed. Patients received 3-tube but without covered stent placement were placed in group A, the remaining patients received covered stent placement with/without 3-tube method were placed in group B. Tubes and stents would be removed once fistula heals. Interventional procedures were technically successful all patients (100%). Esophageal stents and abscess drainage tubes were successfully removed from 14 patients. Three patients underwent stent removal during the perioperative period, resulting in a clinical success rate of 88.5% of 26 patients in group B. A total of 13 complications were found in all patients, including 5 major complications. Patients in group B showed a higher healing rate of abscess cavity and better dysphagia score than group A. During follow up, 17 patients in group A and 11 patients in group B were still alive. Interventional treatment is safe, feasible and efficacious for esophagomediastinal fistula; covered stent placement can promote fistula healing and improve swallowing.


Assuntos
Fístula Esofágica , Fístula , Abscesso/etiologia , Drenagem , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Fístula/etiologia , Fístula/cirurgia , Humanos , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do Tratamento
18.
Int J Biol Sci ; 18(15): 5607-5623, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263174

RESUMO

Immunotherapy treatments harnessing the immune system herald a new era of personalized medicine, offering considerable benefits for cancer patients. Over the past years, tumor neoantigens emerged as a rising star in immunotherapy. Neoantigens are tumor-specific antigens arising from somatic mutations, which are proceeded and presented by the major histocompatibility complex on the cell surface. With the advancement of sequencing technology and bioinformatics engineering, the recognition of neoantigens has accelerated and is expected to be incorporated into the clinical routine. Currently, tumor vaccines against neoantigens mainly encompass peptides, DNA, RNA, and dendritic cells, which are extremely specific to individual patients. Due to the high immunogenicity of neoantigens, tumor vaccines could activate and expand antigen-specific CD4+ and CD8+ T cells to intensify anti-tumor immunity. Herein, we introduce the origin and prediction of neoantigens and compare the advantages and disadvantages of multiple types of neoantigen vaccines. Besides, we review the immunizations and the current clinical research status in neoantigen vaccines, and outline strategies for enhancing the efficacy of neoantigen vaccines. Finally, we present the challenges facing the application of neoantigens.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Vacinas Anticâncer/genética , Vacinas Anticâncer/uso terapêutico , Imunoterapia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Peptídeos , RNA
19.
Front Pharmacol ; 13: 992526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249775

RESUMO

Aim: Drug-eluting beads transarterial chemoembolization (DEB-TACE) has not been widely used in patients with advanced and inoperable lung cancer. We aimed to report the preliminary outcomes of DEB-TACE with gemcitabine-loaded CalliSpheres beads for patients with advanced and inoperable lung cancer. Methods: From November 2017 to October 2021, 37 patients (29 males, mean age 64.7 ± 10.3 years) with advanced and inoperable lung cancer underwent DEB-TACE with gemcitabine-loaded CalliSpheres beads. The primary endpoint was overall response rate, and the secondary endpoints were overall survival and progression-free survival. Results: A total of 54 sessions of DEB-TACE were performed in 37 patients, with a technique success rate of 100%. Fourteen patients received a second session of DEB-TACE. The mean follow-up time was 18.7 ± 11.9 months. After 1, 3, and 6 months, overall response rate and disease control rate were 27.8% and 91.7%, 25.8% and 74.2%, 32.1%, and 67.9%, respectively. The median progression-free survival was 8.8 months (95% CI 7.5, 12.5 months). The 3-, 6- and 12- month progression-free survival rates were 67.1%, 57.0%, and 30.1%, respectively. The median overall survival was 10.0 months (95% CI 4.5, 13.1 months). The 3-, 6-, and 12- month overall survival rates were 88.5%, 72.7%, and 40.9%, respectively. Minor complications were observed in 14 patients (37.8%), with no procedure-related deaths or severe adverse events. Conclusion: DEB-TACE with gemcitabine-loaded CalliSpheres beads is a safe, feasible and effective treatment strategy for patients with advanced and inoperable lung cancer.

20.
Theranostics ; 12(14): 6273-6290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36168626

RESUMO

Chimeric antigen receptor (CAR)-T cell therapy represents a landmark advance in personalized cancer treatment. CAR-T strategy generally engineers T cells from a specific patient with a new antigen-specificity, which has achieved considerable success in hematological malignancies, but scarce benefits in solid tumors. Recent studies have demonstrated that tumor immune microenvironment (TIME) cast a profound impact on the immunotherapeutic response. The immunosuppressive landscape of TIME is a critical obstacle to the effector activity of CAR-T cells. Nevertheless, every cloud has a silver lining. The immunosuppressive components also shed new inspiration on reshaping a friendly TIME by targeting them with engineered CARs. Herein, we summarize recent advances in disincentives of TIME and discuss approaches and technologies to enhance CAR-T cell efficacy via addressing current hindrances. Simultaneously, we firmly believe that by parsing the immunosuppressive components of TIME, rationally manipulating the complex interactions of immunosuppressive components, and optimizing CAR-T cell therapy for each patient, the CAR-T cell immunotherapy responsiveness for solid malignancies will be substantially enhanced, and novel therapeutic targets will be revealed.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Terapia de Imunossupressão , Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T , Microambiente Tumoral
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