Since the publication of MA-20 and EORTC-22922 trials, chest wall (CW)/ whole breast (WB) irradiation + comprehensive regional nodal irradiation (RNI) with internal mammary node irradiation (IMNI) ...has been the standard adjuvant treatment for early-stage breast cancer (BC). However, one size does not fit all BC, and the risk of recurrence significantly varies among this patient population. In addition, whether all BC patients presented with one to three positive lymph nodes (pN1) could benefit from IMNI remains controversial. Thus, the optimal adjuvant RNI volume for early-stage BC with T1-2N1 remains undetermined.
The IMNI PRECISION trial is a single institute, open-labeled, non-inferior, randomized controlled trial. A total of 214 clinically "high risk" BC patients which is characterized as having at least two of the five clinically adverse factors (age ≤ 40, three positive LN, T2 stage, grade 3 and Ki-67 index ≥ 14%), but genomic score "low risk" (the genomic score ≤ 44) N1 breast cancers are randomly assigned to omitting IMNI group (experimental group) or with IMNI (control group) with a 1:1 ratio. The primary endpoint of this trial is event-free survival, and secondary endpoints include overall survival and locoregional recurrence-free survival.
The IMNI PRECISION design allows promising clinical-genomic model to stratify the individualized risk of developing recurrence and guides the optimal RNI treatment for early-stage (pT1-2N1) BC patients. We anticipate that our results would provide high-level evidence to tailor IMNI according to individualized recurrence risk of BC.
ClinicalTrials.gov Identifier NCT04517266 . Date of registration: August 18, 2020. Status: Recruiting.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 (
) plays a crucial role in the occurrence of many diseases. However, ...its role in GC remains unexplored.
The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze
expression in GC.
was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively. The biological functions of
were investigated
and
. Gene microarray, Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms.
was highly expressed in GC and was associated with a poor prognosis.
upregulation significantly promoted the malignant biological behaviors of gastric cancer cell, while
inhibition exerted a opposite effect.
loss can directly inhibit CCND1 and ESR1 expression to downregulate the expression of downstream targets CDK6 and IRS1 and inhibit the proliferation of gastric cancer cells. Moreover,
loss activates IRF7 and DDIT3 to regulate apoptosis in gastric cancer cells.
Our study revealed that
silencing attenuates malignant phenotypes of GC and that it is a potential target for GC treatment.
Titanium dioxide (TiO
2
) has been widely studied in the field of photocatalysis. However, the development of TiO
2
was limited by the photoresponse only in the ultraviolet region and the rapid ...recombination of photogenerated electron–hole pairs. In this work, we prepare a novel TiO
2
and two-dimensional (2D) bismuth selenide (Bi
2
Se
3
) hybrid nanosheets (TiO
2
/Bi
2
Se
3
HNs) via a simple water bath ultrasonic route. X-ray diffraction pattern and Raman spectra were carried out to confirm that as-prepared samples were pure and well crystalized. Besides, TEM characterization proves that 2D Bi
2
Se
3
nanosheets have high specific surface area and it can be clearly observed that the TiO
2
with 60 nm particles are uniformly supported on the surface. Furthermore, photoelectrochemical (PEC) measurements demonstrate that the TiO
2
/Bi
2
Se
3
HNs exhibit excellent photocatalytic performance of 4.3 µA/cm
2
under 100 W of visible light, which were almost 2.5 times that of pure TiO
2
. More importantly, our results show that the photocurrent density was quite stable and only dropped by 10% after 125 cycles. In summary, the improved photocatalytic activity is due to the unique characteristic of 2D Bi
2
Se
3
nanosheets, such as maximized reaction sites and good electrical conductivity, and the positive coupling effect of the TiO
2
/Bi
2
Se
3
heterojunction. These extraordinary properties make the TiO
2
/Bi
2
Se
3
HNs photocatalysts have excellent potential for photocatalytic application.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recent studies have revealed that long non-coding RNAs (lncRNAs) involve in the progression of oral squamous cell carcinoma (OSCC). These lncRNAs have emerged as biomarkers or therapeutic targets for ...OSCC. We here aimed to investigate the role of lncRNA LINC01315 in OSCC and the related mechanisms. LINC01315 and DLG3 were determined to be poorly expressed while microRNA-211 (miR-211) was highly expressed in OSCC tissues and cells using RT-qPCR and western blot analysis. Based on the results obtained from dual-luciferase reporter gene, RIP, and FISH assays, LINC01315 was found to upregulate DLG3 expression by competitively binding to miR-211. Upon altering the expression of LINC01315, and/or miR-211 in OSCC cells with shRNA, mimic, or an inhibitor, we assessed their effects on OSCC cell proliferation, migration, invasion, and apoptosis. LINC01315 knockdown enhanced OSCC cell proliferation, migration and invasion, but dampened their apoptosis, all of which could be reversed by miR-211 inhibition. Elevation of DLG3, a target gene of miR-211, activated the Hippo signaling pathway, whereby suppressing OSCC progression in vitro. Finally, their roles in tumor growth were validated in vivo. These findings suggest that LINC01315 elevates DLG3 expression by competitively binding to miR-211, thereby suppressing OSCC progression.Recent studies have revealed that long non-coding RNAs (lncRNAs) involve in the progression of oral squamous cell carcinoma (OSCC). These lncRNAs have emerged as biomarkers or therapeutic targets for OSCC. We here aimed to investigate the role of lncRNA LINC01315 in OSCC and the related mechanisms. LINC01315 and DLG3 were determined to be poorly expressed while microRNA-211 (miR-211) was highly expressed in OSCC tissues and cells using RT-qPCR and western blot analysis. Based on the results obtained from dual-luciferase reporter gene, RIP, and FISH assays, LINC01315 was found to upregulate DLG3 expression by competitively binding to miR-211. Upon altering the expression of LINC01315, and/or miR-211 in OSCC cells with shRNA, mimic, or an inhibitor, we assessed their effects on OSCC cell proliferation, migration, invasion, and apoptosis. LINC01315 knockdown enhanced OSCC cell proliferation, migration and invasion, but dampened their apoptosis, all of which could be reversed by miR-211 inhibition. Elevation of DLG3, a target gene of miR-211, activated the Hippo signaling pathway, whereby suppressing OSCC progression in vitro. Finally, their roles in tumor growth were validated in vivo. These findings suggest that LINC01315 elevates DLG3 expression by competitively binding to miR-211, thereby suppressing OSCC progression.
Although PD-1/PD-L1 blockade therapy confers salutary effects across cancer types, their efficacy in Extranodal Natural killer/T-cell lymphoma (ENKTCL) patients is limited and unpredictable. Here, we ...comprehensively evaluated the expression profile of a panel of immune-regulatory makers to identify novel prognostic biomarkers and/or therapeutic targets for this malignancy. Using immunohistochemistry and multiplex immunofluorescence, we found that the expression of VISTA (88.1%) was predominantly in CD68+ macrophages and much higher than PD-L1 expression (68.7%) in ENKTCL. B7-H4 and HHLA2 proteins were not detected in ENKTCL. B7-H3 was expressed in minority of ENKTCL patients (13.7%) and mainly colocalized with CD31. A close correlation was detected between VISTA and PD-L1, but they were not co-expressed in the same cells. High expressions of VISTA or PD-L1 were significantly associated with detrimental clinicopathological characteristics, dismal prognosis, and high density of CD8+ TILs, and high VISTA expression was also significantly associated with high density of Foxp3+ TILs. VISTA combined with PD-L1 was an independent prognostic factor for PFS and OS. Moreover, the patients with high VISTA showed a poor response to PD-1 blockades in ENKTCL. In conclusion, these findings provide a rationale for VISTA as an ideal immunotherapeutic target next to PD-L1 for ENKTCL.
Two-dimensional (2D) MoTe
2
nanomaterials have emerged as a promising candidate for constructing excellent supercapacitors due to their high capacitive performance. Recent studies have revealed that ...MoTe
2
has broad prospects as an active material in supercapacitors, although its strict requirements in terms of the external environment and complex preparation process remain serious obstacles to its practical application. Toward this end, MoTe
2
nanosheets (NSs) were prepared by a facile and inexpensive liquid-phase exfoliation approach for the fabrication of MoTe
2
electrodes. The results show that the MoTe
2
NSs exhibit significantly improved electrochemical performance, with a specific capacitance (859 F g
−1
) more than three times that of bulk MoTe
2
(271 F g
−1
) at a current density of 1 A g
−1
. In addition, the MoTe
2
-based electrode showed excellent cycle stability and maintained excellent specific capacitance (92.7% of the initial value) after 1000 cycles under the working condition of a current density of 10 A g
−1
. This study describes a fundamental investigation on the energy storage and conversion properties of 2D layered materials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Lipid nanoparticles with solid matrix have been given increasing attention due to their biodegradable status and ability to entrap a variety of biologically active compounds. In this study, ...new phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor (bFGF) were developed to target the brain via nasal administration. Treatment effects were assessed by quantifying rotational behavior, monoamine neurotransmitter levels and tyrosine hydroxylase expression in 6-hydroxydopamine induced hemiparkinsonian rats. The gelatin nanostructured lipid carriers (GNLs) were prepared by a water-in-water emulsion method and then freeze-dried. The GNLs possessed better profile than gelatin nanoparticles (GNs), with particle size 143 ± 1.14 nm and Zeta potential − 38.2 ± 1.2 mV. The intranasal GNLs efficiently enriched exogenous bFGF in olfactory bulb and striatum without adverse impact on the integrity of nasal mucosa and showed obvious therapeutic effects on hemiparkinsonian rats. Thus, GNLs are attractive carriers for nose-to-brain drug delivery, especially for unstable macromolecular drugs such as bFGF. From the Clinical Editor This team of authors reports the development of phospholipid-based gelatin nanoparticles encapsulating basic fibroblast growth factor to target the brain via intranasal administration. A rat model of hemiparkinsonism was applied demonstrating a good safety profile and an obvious therapeutic effect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
Some studies have indicated that using 500 mg/m2 rituximab combined with CHOP‐14 may be beneficial for elderly men but not women with diffuse large B‐cell lymphoma (DLBCL). The purpose of ...this study was to investigate the potential benefit of escalated doses of rituximab with CHOP‐21 as the first‐line treatment in male patients with DLBCL.
Methods
We performed a retrospective cohort study to analyze the survival benefit of rituximab 500 mg/m2 plus the CHOP‐21 regimen (Escalated‐R‐CHOP‐21) as the first‐line treatment compared with using rituximab 375 mg/m2 plus the CHOP‐21 regimen (Standard‐R‐CHOP‐21) in men with DLBCL. We used propensity score matching to maximize the balance of the observed covariables. The primary endpoints of this study were the progression‐free survival (PFS) rate and overall survival (OS) rate at 3 years.
Results
After a median follow‐up of 47 months (IQR 31–65), no significant difference in PFS and OS was found for men treated with Escalated‐R‐CHOP‐21 compared with Standard‐R‐CHOP‐21 3‐year PFS: 69.7% versus 71.9%, p = 0.867; 3‐year OS: 83.0% versus 82.4%, p = 0.660. After 1:1 propensity score matching, we found that the patients using Escalated‐R‐CHOP‐21 had statistically significant survival benefits relative to Standard‐R‐CHOP‐21 among the 96 matched elderly male patients for 3‐year PFS 75.5% (95% CI 62.8–88.2) versus 58.2% (95% CI 44.3–72.1); p = 0.019 and 3‐year OS 86.6% (95% CI 76.4–96.8) versus 65.8% (95% CI 52.1–79.5); p = 0.017. However, no differences in survival were observed for younger male patients. Furthermore, the dose effect in PFS of Escalated‐R‐CHOP‐21 was more obvious for elderly male patients with no high‐risk extranodal sites (p = 0.005 and interaction p = 0.030).
Conclusion
Escalated‐R‐CHOP‐21 could be a safe and effective option for treating elderly male patients with DLBCL. This study provides new insight into optimizing the standard treatment regimen, which may have important therapeutic implications in elderly male patients with DLBCL.
In this study, we investigated the potential benefit of rituximab 500 mg/m2 plus the CHOP‐21 regimen (Escalated‐R‐CHOP‐21) as the first‐line treatment compared with using rituximab 375 mg/m2 plus the CHOP‐21 regimen (Standard‐R‐CHOP‐21) in male patients with DLBCL. We found that only elderly men had statistically significant survival benefits from Escalated‐R‐CHOP‐21 than Standard‐R‐CHOP‐21 of 3‐year PFS 75.5% (95% CI 62.8–88.2) vs. 58.2% (95%CI 44.3–72.1); p = 0.019 and 3‐year OS 86.6% (95% CI 76.4–96.8) vs. 65.8.0% (95% CI 52.1–79.5); p = 0.017 without causing severe toxicity after propensity score matching.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lacking quantitative evaluations of clinicopathological features and the risk factors for loco-regional recurrence (LRR) in gastric cancer after D2 gastrectomy, we aimed to develop a competing risk ...nomogram to identify the risk predictors for initial LRR.
We retrospectively analysed 1105 patients who underwent radical gastrectomy with D2 resection for stage I-III gastric cancer. A nomogram predicting initial LRR of gastric cancer was conducted based on Fine and Grey's competing risk analysis. The predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index) and calibration curve. Decision tree analysis was performed for patient grouping.
At a median follow-up of 28.4 months, 274 patients developed 373 first recurrence events (local, regional, and distant disease). The median recurrence-free survival (RFS) was 16.7 months. Multivariate competing risk analysis showed that age (SHR, 1.72; 95% CI, 1.10-2.83, p = 0.031), CEA (SHR, 1.94; 95% CI, 1.09-3.46, p = 0.024), pT4 (SHR, 2.77; 95% CI, 1.01-7.57, p = 0.047), lymph node metastasis (SHR 1.92, 95% CI: 1.09-3.38, p = 0.024) and LVI (SHR, 1.84; 95% CI, 1.06-3.20, p = 0.028) were independent risk factors for LRR (all p < 0.05). The nomogram incorporating these factors achieved good agreement between prediction and actual observation with a concordance index of 0.738 (95% CI, 0.767 to 0.709). In a subgroup analysis of node-positive patients, pN3b was associated with increased peritoneal and distant metastasis (p = 0.048). The para-aortic lymph nodes were the most frequent sites (n = 71) of LRR, and among them, the 16a2 and 16b1 nodes exhibited even more prevalence (90.1 and 81.7%).
Adjuvant radiotherapy might be recommended in gastric cancer patients ≥65 years old or those with pN+, pT4, LVI, or increased CEA levels, particularly in high-risk or pN1-3a patients. The competing risk nomograms may be considered as convenient and individualized predictive tools for LRR in gastric cancer after D2 gastrectomy. It is also recommended that the clinical target volume (CTV) include 16a2 and 16b1 regions of para-aortic lymph nodes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
IntroductionShort course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40–42.5 Gy in 15–16 ...fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique.Methods and analysisThis is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life.Ethics and disseminationThe study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03829553.
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