In this work, an integrated electrode system consisting of a graphene working electrode, a carbon counter electrode and an Ag/AgCl reference electrode was fabricated on an FR-4 glass fiber plate by a ...polyethylene self-adhesive mask stencil method combined with a manual screen printing technique. The integrated graphene electrode was used as the base electrode, and AuNPs were deposited on the working electrode surface by cyclic voltammetry. Then, the carcinoembryonic antigen aptamer was immobilized using the sulfhydryl self-assembly technique. The sensor uses Fe(CN)
as a redox probe for label free detection of carcinoembryonic antigen based on the impedance change caused by the difference in electron transfer rate before and after the binding of carcinoembryonic antigen aptamer and the target carcinoembryonic antigen. The results showed a good linear relationship when the CEA concentration is in the range of 0.2-15.0 ng/ml. The detection limit was calculated to be 0.085 ng/ml (S/N = 3).
The aim of the present study is to evaluate the safety and efficacy of iodine-125 brachytherapy for newly diagnosed brain metastasis in patients with non-small cell lung cancer (NSCLC).
The study ...included 158 NSCLC patients diagnosed with brain metastasis from December 2003 to August 2017. Ninety-nine patients underwent external beam radiotherapy (EBRT group), and 59 patients received iodine-125 brachytherapy (
I group). In addition, the 6- and 12-month progression-free survival (PFS) rates and the 12- and 24-month overall survival (OS) rates were compared between the EBRT group and the
I group. Median OS and PFS were analyzed using the Kaplan-Meier method with a log-rank test.
The 6-month PFS rate was significantly higher in the
I group (
= 0.002) than in the EBRT group, while no differences were found in the 12-month PFS rate (
= 0.184). Additionally, the 12- (
= 0.839) and 24-month (
= 0.284) OS rates were not significantly different between the two groups. No significant differences in median OS (
= 0.525) or PFS (
= 0.425) were found between the two groups.
Iodine-125 brachytherapy is an alternative therapy for patients unable to undergo surgical resection.
Background
Patients with extensive‐stage small cell lung cancer (ES‐SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide‐platinum is recommended ...as standard first‐line therapy. However, which combination pattern is the best still remains unknown. This network meta‐analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients.
Methods
Hazard ratios (HRs) and odds ratios (ORs) were generated using R software. The outcomes of overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (grade ≥ 3 adverse events AEs) were analyzed.
Results
A total of 10 randomized controlled trials (RCTs) involving 5544 patients were included for analysis. Drug combination patterns included adebrelimab, atezolizumab, durvalumab, durvalumab plus tremelimumab, ipilimumab, pembrolizumab, serplulimab, benmelstobart plus anlotinib, tislelizumab, tiragolumab plus atezolizumab and toripalimab in combination with chemotherapy. The novel antiangiogenic agent containing regimen benmelstobart + anlotinib + chemotherapy showed the highest possibility to present the best PFS and OS versus chemotherapy. Compared with ICI plus chemotherapy, it also achieved significantly better PFS and presented a tendency of OS benefit. As for safety and toxicity, patients treated with benmelstobart + anlotinib + chemotherapy and durvalumab + tremelimumab + chemotherapy suffered a higher likelihood of more grade ≥ 3 AEs without unexpected AEs.
Conclusion
PD‐1/PD‐L1 inhibitors‐based combinations are associated with significant improvement in both PFS and OS for treatment‐naïve ES‐SCLC patients. Benmelstobart plus anlotinib with chemotherapy (CT) yielded better survival benefit versus CT alone or other ICIs + CT with caution for more adverse effects along with the addition of an antiangiogenic agent.
We compared the efficacy and safety of currently available ICI‐based regimens, and investigated the most appropriate therapy for treatment‐naïve ES‐SCLC patients. PD‐1/PD‐L1 inhibitors‐based combinations are associated with significant improvement in both PFS and OS. The novel antiangiogenic agent containing regimen benmelstobart, anlotinib and chemotherapy further improved survival with more but manageable adverse events.
e20619 Background: As a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib demonstrated superior progression-free survival and a ...well-tolerated toxicity profile to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, the real-world impact of aumolertinib in the first-line treatment on patients' HRQoL still remains unclear. Methods: Advanced NSCLC patients with sensitizing EGFR mutations treated with aumolertinib 110 mg daily in the first-line treatment were prospectively enrolled and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and EORTC Quality of Life lung cancer-specific module (QLQ-LC13) information were collected. Efficacy evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was also recorded here. Prespecified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling hands or feet, chest pain, arm or shoulder pain and pain of other sites. Results: Totally, 33 patients in the first-line treatment were included and 23 patients had efficacy information up to Jan 2024. The median follow-up time was 264 days (interval: 36-491 days). The objective response rate (ORR) and disease control rate (DCR) was 65.2% and 91.3%, respectively. All the patients haven’t reached the time to deterioration and the progression free survival(PFS) and overall survival is not reach. EORTC QLQ-LC30 showed general health status scale and functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by EORTC QLQ-LC13 showed cough, sore mouth or tongue, chest pain, arm or shoulder pain and pain of other sites, were improved significantly after aumolertinib treatment (P < 0.05). Conclusions: General health status, functional status and key symptoms improved from baseline in patients with advanced NSCLC receiving aumolertinib as first-line treatment. The ORR and DCR in our study was comparable in those showed the AENEAS trial.
e14558
Background: TGFBR2 encodes a receptor kinase which signals to downstream effectors in the TGF-ß signaling pathway. Recent research has shown that truncation mutations of TGFBR2 in gastric ...cancer with high tumor mutational burden. However, the relationship remains unclear in other solid tumors. Methods: We retrospectively analyzed the TGFBR2 mutations of 19370 Chinese patients with pan-cancer during 2019-2022 (Simcere Diagnosis, Nanjing, China) Next-generation sequencing (NGS) assessed somatic mutations in tumor tissue. We figured out TGFBR2 mutation frequency, TMB and MSI in TGFBR2-mutant, TGFBR2 wild-type. Results: We have detected TGFBR2 mutants in 536 (2.8%) samples. The top 5 frequent cancers were colorectal cancer (132, 24.7%), lung cancer (118, 22%), gastric cancer (78, 14.5%), biliary tract tumors(52, 9.7%) liver cancer (33, 6.2%).TGFBR2 variants included missense/indel/insert (238, 44.4%), truncation (219, 40.9%), splicing site variant (23, 4.3%), and CNV (33, 6.2%).The inactive variants include missense, which occurs in the TGFBR2 serine/threonine kinase domain, truncation and splicing site variant. However, truncation was the most common type, recurring in a few hot spots (p.K153Sfs*35, p.K153Afs*3, p.R520* ). And we found that the TMB and MSI in the TGFBR2 mutation group was significantly higher than that in the TGFBR2 wild-type group TMB-H (TMB ≥10 musts/Mb): TGFBR2-MUT vs TGFBR2-WT, 41.2% vs 9.5%, p < 0.01; MSI-H: TGFBR2-MUT vsTGFBR2-WT, 27.4% vs1.7% p < 0.01. In the TGFBR2 mutation group, It was also observed that TMB and MSI in the TGFBR2 truncation or splicing site mutant (INACT) group was significantly higher than that in the other mutant types (VUS) group TMB-H (TMB ≥10 musts/Mb): TGFBR2-INACT vs TGFBR2-VUS, 51.0% vs 27.9%, p < 0.01; MSI-H: TGFBR2-INACT vs TGFBR2-VUS 39.4% vs 10.6% p < 0.01. And then, we separately analyzed the correlation between MSI, TMB and TGFBR2 gene mutation in the top 5 frequent cancers. Over 60% of patients with TGFBR2 mutations in colorectal cancers have high TMB and MSI values TMB-H (TMB ≥10 musts/Mb): TGFBR2-MUT vs TGFBR2-WT, 71.3% vs 12.8%, p < 0.01; MSI-H: TGFBR2-MUT vs TGFBR2-WT, 61.2% vs 3.0% p < 0.01. Conclusions: We analyzed the distribution of TGFBR2 mutants in Chinese patients with solid tumors. Our data showed that TGFBR2 mutant was significantly associated with TMB-H and MSI-H, and this may be a potential molecular marker of immunotherapy. And studies have shown that the combination of TGF-β inhibitors and immune checkpoint inhibitors can increase the killing effect of T cells on tumors. In short, detection of TGFBR2 mutation has certain clinical significance.
Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of ...maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen.
We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy.
Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8-12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0-7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed.
MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.
Collagen is one of the most useful biopolymers because of its low immunogenicity and biocompatibility. The biomedical potential of natural collagen is limited by its poor mechanical strength, thermal ...stability, and enzyme resistance, but exogenous chemical, physical, or biological crosslinks have been used to modify the molecular structure of collagen to minimize degradation and enhance mechanical stability. Although crosslinked collagen-based materials have been widely used in biomedicine, there is no standard crosslinking protocol that can achieve a perfect balance between stability and functional remodeling of collagen. Understanding the role of crosslinking agents in the modification of collagen performance and their potential biomedical applications are crucial for developing novel collagen-based biopolymers for therapeutic gain.
Multiple crosslinking techniques have been developed to optimize the properties of fibrillar collagen for different biotechnological applications.
Treatments based on modulating crosslinks within the collagen matrix of damaged tissues have received excellent clinic results for treating diseases such as keratoconus.
Crosslinked collagen-based scaffolds have been extensively studied for tissue engineering to promote tissue regeneration or repair.
Nanoparticles act as crosslinking agents for collagen stabilization as well as functionalized carriers for crosslinking to collagen scaffolds for novel biomolecular applications.
Drought is one of the most severe environmental stresses affecting plant growth and limiting crop production. Although many genes involved in adaptation to drought stress have been disclosed, the ...relevant molecular mechanisms are far from understood. This study describes an Arabidopsis gene, ASPG1 (ASPARTIC PROTEASE IN GUARD CELL 1), that may function in drought avoidance through abscisic acid (ABA) signalling in guard cells. Overexpression of the ASPG1 gene enhanced ABA sensitivity in guard cells and reduced water loss in ectopically overexpressing ASPG1 (ASPG1-OE) transgenic plants. In ASPG1-OE plants, some downstream targets in ABA and/or drought-signalling pathways were altered at various levels, suggesting the involvement of ASPG1 in ABA-dependent drought avoidance in Arabidopsis. By analysing the activities of several antioxidases including superoxide dismutase and catalase in ASPG1-OE plants, the existence was demonstrated of an effective detoxification system for drought avoidance in these plants. Analysis of ProASPG1-GUS lines showed a predominant guard cell expression pattern in various aerial tissues. Moreover, the protease activity of ASPG1 was characterized in vitro, and two aspartic acid sites, D180 and D379, were found to be key residues for ASPG1 aspartic protease activity in response to ABA. In summary, these findings suggest that functional ASPG1 may be involved in ABA-dependent responsiveness and that overexpression of the ASPG1 gene can confer drought avoidance in Arabidopsis.
The Ni1.5Co1.5S4@Ti3C2 hybrid materials with different MXene contents have been synthesized through in-situ growing Ni1.5Co1.5S4 nanoparticles on few-layer Ti3C2 nanoflakes using a simple one-step ...hydrothermal method. The supercapacitive performances of the hybrid materials are optimized by tuning the composition of the hybrid materials from the atomic ratios of nickel and cobalt to content of heterogeneous components. Owing to achieving the maximum of synergistic effects at multi-scales, the Ni1.5Co1.5S4@Ti3C2-5 electrode shows a high specific capacitance of 166.7 mAh g−1 at the current density of 1 A g−1, and superior rate capability with capacitance retention rate of 73.9% after a 20 time increase in current densities. Impressively, an asymmetric supercapacitor, assembled with Ni1.5Co1.5S4@Ti3C2-5 as positive electrode and activated carbon as negative electrode, delivers high energy density of 49.8 Wh kg−1 at a power density of 800 W kg−1, and an excellent cycling stability of 90% capacitance retention after 8000 cycles at 10 A g−1, demonstrating a great prospect for practical applications in the fields of energy storage.
Interstitial fluid pressure (IFP) in tumor is much higher than that in normal tissue, and it constitutes a great obstacle for the delivery of antitumor drugs, thus becoming a potential target for ...cancer therapy. In this study, cationic nanostructured lipid carriers (NLCs) were modified by low molecular weight gelatin to achieve the desirable reduction of tumor IFP and improve the drug delivery. In this way, the chemotherapy of formulations on tumor proliferation and pulmonary metastasis was further improved. The nanoparticles were used to load three drugs, docetaxel (DTX), quercetin (Qu), and imatinib (IMA), with high encapsulation efficiency of 89.54%, 96.45%, and 60.13%, respectively. GNP-DTX/Qu/IMA nanoparticles exhibited an enzyme-sensitive drug release behavior, and the release rate could be mediated by matrix metalloproteinases (MMP-9). Cellular uptake and MTT assays showed that the obtained GNP-DTX/Qu/IMA could be internalized into human breast 4T1 cells effectively and exhibited the strongest cytotoxicity. Moreover, GNP-DTX/Qu/IMA demonstrated obvious advantages in inducing apoptosis and mediating the expression of apoptosis-related proteins (Caspase 3, Caspase 9, and bcl-2). In the wound-healing assay, GNP-DTX/Qu/IMA exhibited evidently inhibition of cell migration. The benefits of tumor IFP reduction induced by GNP-DTX/Qu/IMA were further proved after a continuous administration to 4T1 tumor-bearing mice. Finally, in the in vivo antitumor assays, GNP-DTX/Qu/IMA displayed stronger antitumor efficiency as well as suppression on pulmonary metastasis. In conclusion, the GNP-DTX/Qu/IMA system might be a promising strategy for metastatic breast cancer treatment.
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