RÉSUMÉ
BACKGROUND: An evaluation of scapula position is important to predict spine curvature and shoulder function in patients with adolescent idiopathic scoliosis (AIS). Therefore, a reliable scapula position is required to assess posture in patients with AIS. OBJECTIVE: This study investigated the reliabilities of scapula position tests and differences in scapula position and shoulder function between individuals with and without AIS. METHODS: The study compared 18 patients with AIS and 18 healthy controls to identify differences in scapula position and shoulder function. The acromion-table distance, lateral displacement of the scapula, acromion depression, winged scapula, upward rotation of the scapula, and anterior tilt of the scapula were measured. Scapula position test reliabilities were assessed using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimum clinically important difference (MCID). Shoulder function was measured using the Shoulder Pain and Disability Index. RESULTS: The reliabilities of scapula position tests (ICC 0.85-0.93, SEM 0.1-1.2, and MCID 0.2-2.5) were good. There were significant differences in scapula position and shoulder function between patients with AIS and healthy controls (p< 0.05). CONCLUSION: Scapula position tests were highly reliable in patients with AIS; they can be used to evaluate scapula position during clinical assessment of posture in patients with AIS.
RÉSUMÉ
PURPOSE: The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC. MATERIALS AND METHODS: Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05). CONCLUSION: Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.
Sujet(s)
Protocoles de polychimiothérapie antinéoplasique , Tumeurs des canaux biliaires , Chimioradiothérapie , Cholangiocarcinome , Cisplatine , Désoxycytidine , , Humains , Cholangiocarcinome/thérapie , Cholangiocarcinome/mortalité , Cholangiocarcinome/anatomopathologie , Cholangiocarcinome/traitement médicamenteux , Désoxycytidine/analogues et dérivés , Désoxycytidine/administration et posologie , Désoxycytidine/usage thérapeutique , Mâle , Femelle , Adulte d'âge moyen , Cisplatine/administration et posologie , Cisplatine/usage thérapeutique , Sujet âgé , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs des canaux biliaires/thérapie , Tumeurs des canaux biliaires/mortalité , Tumeurs des canaux biliaires/anatomopathologie , Adulte , Chimioradiothérapie/méthodes , Résultat thérapeutique , Pronostic , Sujet âgé de 80 ans ou plus , Études rétrospectives , Dosimétrie en radiothérapie , Estimation de Kaplan-Meier , Stadification tumoraleRÉSUMÉ
A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.
Sujet(s)
Tumeurs du sein , Carcinome intracanalaire non infiltrant , Humains , Femelle , Carcinome intracanalaire non infiltrant/radiothérapie , Carcinome intracanalaire non infiltrant/chirurgie , Carcinome intracanalaire non infiltrant/anatomopathologie , Mastectomie partielle , Études rétrospectives , Récidive tumorale locale/chirurgie , Marges d'exérèse , Dose de rayonnement , Tumeurs du sein/radiothérapie , Tumeurs du sein/chirurgieRÉSUMÉ
PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.
Sujet(s)
Tumeurs du sein , Humains , Femelle , Tumeurs du sein/imagerie diagnostique , Tumeurs du sein/radiothérapie , Tumeurs du sein/chirurgie , Région mammaire/imagerie diagnostique , Mastectomie partielle , Tomodensitométrie/méthodesRÉSUMÉ
PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.
Sujet(s)
Tumeurs du sein , Apprentissage profond , Humains , Femelle , Tumeurs du sein/imagerie diagnostique , Planification de radiothérapie assistée par ordinateur/méthodes , Organes à risque , Région mammaire/imagerie diagnostiqueRÉSUMÉ
PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.
Sujet(s)
Tumeurs des canaux biliaires , Conduits biliaires extrahépatiques , Humains , Pronostic , Chimioradiothérapie adjuvante/méthodes , Tumeurs des canaux biliaires/chirurgie , Conduits biliaires extrahépatiques/chirurgie , Conduits biliaires extrahépatiques/anatomopathologie , Facteurs de risque , Études rétrospectivesRÉSUMÉ
BACKGROUND: Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells. METHODS: Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated ß-galactosidase (SA-ß-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-ß-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model. RESULTS: Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-ß-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-ß-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength. CONCLUSIONS: Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.
RÉSUMÉ
AIM: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. METHODS: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. RESULTS: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. CONCLUSION: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.
Sujet(s)
Tumeurs du sein , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Carboplatine , Docetaxel , Études rétrospectives , Récidive tumorale locale/anatomopathologie , Traitement néoadjuvant , Trastuzumab/usage thérapeutiqueRÉSUMÉ
PURPOSE: Data on subsequent arm lymphedema (SAL) after salvage treatment for locoregional recurrence (LRR) of breast cancer are limited. We conducted a study to evaluate the risk of SAL in patients with LRR. METHODS: We reviewed the data of patients with breast cancer who had LRR and were initially diagnosed between January 2003 and December 2017. Among the 214 patients who received curative salvage treatment, most had local (n = 125, 57.9%), followed by regional (n = 73, 34.1%), and locoregional (n = 16, 7.9%) recurrences. A competing risk analysis considering the factors of death and a second LRR were performed to exclude potential malignant lymphedema. We used the Fine-Gray subdistribution hazards model to estimate the hazard ratio (HR) for comparing the risk of SAL. RESULTS: With a median follow-up duration of 41.4 months (interquartile range, 25.6-65.1), 51 patients (23.8%) experienced SAL with a median interval of 9.9 months after treatment. The two-year cumulative incidence of SAL was 12.7%. Among the 18 patients with initial lymphedema, nine (50.0%) developed SAL. Multivariate analysis revealed that a history of lymphedema (HR, 4.61; p < 0.001) and taxane-based salvage chemotherapy (HR, 2.38; p = 0.009) were significantly associated with SAL development. CONCLUSION: Salvage treatment for LRR-induced SAL was performed in 24% of the patients. A history of initial lymphedema and salvage taxane-based chemotherapy increases the risk of developing SAL. Therefore, close surveillance for the incidence of SAL is required in patients opting for salvage treatment for LRR.
RÉSUMÉ
AIM: Patients with locoregionally uncontrolled breast tumors are frequently referred for breast palliative radiotherapy (PRT) to mitigate symptoms. We analyzed the outcomes following breast PRT to optimize PRT according to risk groups. METHODS: We reviewed 133 patients who underwent breast PRT. A median total dose of 45 Gy was prescribed with an equivalent dose in 2 Gy fractions (EQD2, α/ß = 3.5) of 53 Gy. The Cox proportional hazards model was used to analyze the prognostic factors of local control (LC). RESULTS: Most (90.2%) had polymetastatic disease (> 5 lesions), and 48.9% had bone metastasis. With a median follow-up of 17.2 months, the 2-year LC and overall survival (OS) rates were 49.4%, and 48.3%, respectively. Multivariable analyses demonstrated progressive or mixed responses outside the breast and > 2 lines of previous therapy as adverse features for clinical outcomes. Group 1 (0 risk factors) showed favorable 2-year LC and OS of 63.9%, and 72.8%, respectively, whereas group 3 (2 risk factors) showed the worst outcomes of 0%, and 6.8%, respectively. Breast PRT with EQD2 ≥ 63 Gy showed a significant benefit in LC for group 1 and marginal benefit (p = 0.055) for group 2, but no improvement for group 3 (p = 0.300). CONCLUSION: Breast PRT showed favorable LC outcomes in patients with stable disease outside the breast and treated with ≤ 2 lines of systemic treatment. Our findings warrant future clinical trials investigating the role of higher than palliative dose and early intervention of PRT in stage IV patients.
Sujet(s)
Tumeurs osseuses , Tumeurs du sein , Humains , Femelle , Tumeurs du sein/radiothérapie , Dosimétrie en radiothérapie , Tumeurs osseuses/radiothérapie , Région mammaire , Fractionnement de la dose d'irradiation , Études rétrospectivesRÉSUMÉ
The HyperArc technique is known for generating high-quality radiosurgical treatment plans for intracranial lesions or hippocampal-sparing whole-brain radiotherapy (WBRT). However, there is no reported feasibility of using the HyperArc technique in hippocampal-sparing WBRT with a simultaneous integrated boost (SIB). This study aimed to compare dosimetric parameters of 2 commercially-available volumetric-modulated arc radiotherapy techniques, HyperArc and RapidArc, when using hippocampal-sparing WBRT with a SIB to treat brain metastases. Treatment plans using HyperArc and RapidArc techniques were generated retrospectively for 19 previously treated patients (1 to 3 brain metastases). The planning target volumes for the whole brain (excluding the hippocampal avoidance region; PTVWB) and metastases (PTVmet) were prescribed 25 and 45 Gy, respectively, in 10 fractions. Each plan included homogeneous and inhomogeneous delivery to the PTVmet. Dosimetric parameters for the target (conformity index [CI], homogeneity index [HI], target coverage [D95%]), and nontarget organs at risk were compared for the HyperArc and RapidArc plans. For homogeneous delivery, dosimetric parameters, including mean CI, HI, and target coverage in PTVWB and PTVmet, were superior for HyperArc than RapidArc plans (all p < 0.01). The PTVWB and PTVmet target coverage for HyperArc plans was significantly greater than for RapidArc plans (96.17% vs 93.38%, p < 0.01; 94.02% vs 92.21%, p < 0.01, respectively). HyperArc plans had significantly lower mean hippocampal Dmax and Dmin values than RapidArc plans (Dmax: 15.53 Gy vs, 16.71 Gy, p < 0.01; Dmin: 8.33 Gy vs 8.93 Gy, p < 0.01, respectively). Similarly, inhomogeneous delivery of hyperArc produced a superior target and lower hippocampal dosimetric parameters than RapidArc, except for the HI of PTVmet (all p < 0.01). HyperArc generated superior conformity and target coverage with lower hippocampal doses than RapidArc. HyperArc could be an attractive technique for hippocampal-sparing WBRT with an SIB.
RÉSUMÉ
PURPOSE: Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins. METHODS: We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2 Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25 Gy for positive margins and 59.31-61.81 Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed. RESULTS: After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n = 55) and 2.4% in the negative margin group (n = 495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p = 0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p = 0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p = 0.426). CONCLUSION: In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings.
Sujet(s)
Tumeurs du sein , Humains , Sujet âgé , Femelle , Tumeurs du sein/radiothérapie , Tumeurs du sein/chirurgie , Tumeurs du sein/anatomopathologie , Mastectomie partielle , Études rétrospectives , Dosimétrie en radiothérapie , Récidive tumorale locale/chirurgieRÉSUMÉ
BACKGROUND: We evaluated the impact of omitting axillary lymph node dissection (ALND) on oncological outcomes in breast cancer patients with residual nodal disease after neoadjuvant chemotherapy (NAC). METHODS: The medical records of patients who underwent NAC followed by surgical resection and had residual nodal disease were retrospectively reviewed. In total, 1273 patients from 12 institutions were included; all underwent postoperative radiotherapy. Axillary surgery consisted of ALND in 1103 patients (86.6%) and sentinel lymph node biopsy (SLNBx) alone in 170 (13.4%). Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed before and after propensity score matching (PSM). RESULTS: The median follow-up was 75.3 months (range, 2.5-182.7). Axillary recurrence rates were 4.8% in the ALND group (n = 53) and 4.7% in the SLNBx group (n = 8). Before PSM, univariate analysis indicated that the 5-year OS rate was inferior in the ALND group compared to the SLNBx group (86.6% vs. 93.3%, respectively; P = 0.002); multivariate analysis did not show a difference between groups (P = 0.325). After PSM, 258 and 136 patients were included in the ALND and SLNBx groups, respectively. There were no significant differences between the ALND and SLNBx groups in DFS (5-year rate, 75.8% vs. 76.9%, respectively; P = 0.406) or OS (5-year rate, 88.7% vs. 93.1%, respectively; P = 0.083). CONCLUSIONS: SLNBx alone did not compromise oncological outcomes in patients with residual nodal disease after NAC. The omission of ALND might be a possible option for axillary management in patients treated with NAC and postoperative radiotherapy.
Sujet(s)
Tumeurs du sein , Noeud lymphatique sentinelle , Humains , Femelle , Tumeurs du sein/chirurgie , Traitement néoadjuvant , Études rétrospectives , Métastase lymphatique/anatomopathologie , Lymphadénectomie/effets indésirables , Biopsie de noeud lymphatique sentinelle , Noeuds lymphatiques/anatomopathologie , Aisselle/anatomopathologie , Maladie résiduelle/anatomopathologie , Noeud lymphatique sentinelle/anatomopathologieRÉSUMÉ
We recently reported that lactoferrin (LF) induces Foxp3+ Treg differentiation through binding to TGFß receptor III (TßRIII), and this activity was further enhanced by TGFß1. Generally, a low T-cell receptor (TCR) signal strength is favourable for Foxp3+ Treg differentiation. In the present study, we explored the effect of lactoferrin chimera (LFch, containing lactoferricin [aa 17-30] and lactoferrampin [aa 265-284]), along with TGFß1 on Foxp3+ Treg differentiation. LFch alone did not induce Foxp3 expression, yet LFch dramatically enhanced TGFß1-induced Foxp3 expression. LFch had little effect on the phosphorylation of Smad3, a canonical transcriptional factor of TGFß1. Instead, LFch attenuated the phosphorylation of S6 (a target of mTOR), IκB and PI3K. These activities of LFch were completely abrogated by pretreatment of LFch with soluble TGFß1 receptor III (sTßRIII). Consistent with this, the activity of LFch on TGFß1-induced Foxp3 expression was also abrogated by treatment with sTßRIII. Finally, the TGFß1/LFch-induced T cell population substantially suppressed the proliferation of responder CD4+ T cells. These results indicate that LFch robustly enhances TGFß1-induced Foxp3+ Treg differentiation by diminishing TCR/CD28 signal intensity.
Sujet(s)
Antigène CD28 , Lymphocytes T régulateurs , Lymphocytes T régulateurs/métabolisme , Lactoferrine/pharmacologie , Lactoferrine/métabolisme , Récepteurs aux antigènes des cellules T/métabolisme , Différenciation cellulaire , Facteurs de transcription Forkhead/génétique , Facteurs de transcription Forkhead/métabolismeRÉSUMÉ
The buffering capacity of buffer agents and their effects on in vitro and in vivo rumen fermentation characteristics, and bacterial composition of a high-concentrate fed Hanwoo steers were investigated in this study. Treatments were comprised of CON (no buffer added), BC0.3% (low buffering capacity, 0.3% buffer), BC0.5% (medium buffering capacity, 0.5% buffer), and BC0.9% (high buffering capacity, 0.9% buffer). Four Hanwoo steers in a 4 × 4 Latin square design were used for the in vivo trial to assess the effect of treatments. Results on in vitro experiment showed that buffering capacity, pH, and ammonia-nitrogen concentration (NH3-N) were significantly higher in BC0.9% and BC0.5% than the other treatments after 24 h incubation. Individual and total volatile fatty acids (VFA) concentration of CON were lowest compared to treatment groups. Meanwhile, in vivo experiment revealed that Bacteroidetes were dominant for all treatments followed by Firmicutes and Proteobacteria. The abundances of Barnesiella intestinihominis, Treponema porcinum, and Vibrio marisflavi were relatively highest under BC0.9%, Ruminoccocus bromii and Succiniclasticum ruminis under BC0.5%, and Bacteroides massiliensis under BC0.3%. The normalized data of relative abundance of observed OTUs' representative families have grouped the CON with BC0.3% in the same cluster, whereas BC0.5% and BC0.9% were clustered separately which indicates the effect of varying buffering capacity of buffer agents. Principal coordinate analysis (PCoA) on unweighted UniFrac distances revealed close similarity of bacterial community structures within and between treatments and control, in which BC0.9% and BC0.3% groups showed dispersed community distribution. Overall, increasing the buffering capacity by supplementation of BC0.5% and and BC0.9% buffer agents enhanced rumen fermentation characteristics and altered the rumen bacterial community, which could help prevent ruminal acidosis during a high-concentrate diet.
Sujet(s)
Microbiote , Rumen , Humains , Animaux , Fermentation , Proteobacteria , FirmicutesRÉSUMÉ
The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p⟨0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC.
Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/anatomopathologie , Phosphatidylinositol 3-kinases/métabolisme , Phosphatidylinositol 3-kinase , Tumeurs du poumon/métabolisme , Isoformes de protéines , PronosticRÉSUMÉ
BACKGROUND: Several studies have reported patient-related risk factors for late rectal bleeding following conventionally fractionated radiotherapy for prostate cancer. We investigated patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy. METHODS: A total of 231 patients with local or locally advanced prostate cancer treated with hypofractionated radiotherapy (70 or 67.2 Gy in 28 fractions) were evaluated retrospectively. All patients received intensity-modulated radiotherapy with daily image guidance. The relationships between late rectal bleeding and risk factors like diabetes, hypertension, cirrhosis, and anticoagulant use were analyzed. RESULTS: During a median follow-up of 23 months, the crude rates of grade ≥ 1, grade ≥ 2, and grade ≥ 3 late rectal bleeding were 23.8%, 16.9%, and 9.5%, respectively. Cirrhosis and anticoagulant use predicted an increased risk of grade ≥ 3 rectal bleeding in multivariable analyses (hazard ratio [HR] 14.37, 95% confidence interval [CI] 3.09-66.87, P = 0.001, and HR 2.93, 95% CI 1.14-7.55, P = 0.026, respectively). The non-anticoagulant group had a significantly superior 5-year freedom from grade ≥ 3 bleeding compared to the anticoagulant group in a propensity-weighted log-rank analysis (88.0% vs. 76.7%, P = 0.041). A receiver operating characteristic curve analysis revealed that rectal bleeding was minimized in the anticoagulant group if the equivalent dose at fractionation of 2 Gy (EQD2) V77 Gy of the rectum was < 4.5% or if the EQD2 V8.2 Gy was < 71.0%. CONCLUSIONS: Patients taking anticoagulants or those with cirrhosis had a significantly higher risk of severe late rectal bleeding than other patients after hypofractionated radiotherapy for prostate cancer in the present study. The bleeding risk could be lowered by minimizing hotspots in patients taking anticoagulants.
Sujet(s)
Hémorragie/étiologie , Tumeurs de la prostate/radiothérapie , Hypofractionnement de dose , Lésions radiques/étiologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Hémorragie/épidémiologie , Humains , Mâle , Adulte d'âge moyen , Tumeurs de la prostate/anatomopathologie , Lésions radiques/épidémiologie , Rectum , Études rétrospectives , Facteurs de risqueRÉSUMÉ
PURPOSE: To investigate the impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM). METHODS: After a retrospective review of patients treated with PMRT between 2008 and 2017, we included 153 patients who underwent iBR and 872 patients who did not undergo iBR. Among the 153 patients who underwent iBR, 34 received one-stage iBR with autologous tissue and 119 received two-stage iBR. Conventional fractionated PMRT with a total dose of 50-50.4 Gy in 25-28 fractions was performed in all patients. Propensity scores were calculated via logistic regression. RESULTS: Patients who underwent iBR were younger, had early stage disease, and had more frequent hormone receptor-positive tumor than those who did not undergo iBR. After PSM, 127 patients from each group with well-balanced characteristics were selected. With a median follow-up of 67.5 months, iBR led to better 6-year disease-free survival rates compared to no iBR before PSM (84.8% vs. 71.4%, p = 0.003); after PSM, there was no significant difference (84.8% vs. 75.5%, p = 0.130). On multivariable analysis in the matched cohort, iBR was not associated with inferior disease-free survival (hazard ratio, 0.67; p = 0.175). In the sensitivity analysis, iBR was not associated with a lower disease-free survival across all prognostic groups. The 5-year cumulative incidence of iBR failure was 15.0%. CONCLUSION: In patients with adverse pathologic factors planning to receive PMRT, iBR did not compromise oncologic outcomes. In addition, iBR can be considered in patients treated with PMRT with several clinicopathologic risk factors.
Sujet(s)
Tumeurs du sein , Mammoplastie , Tumeurs du sein/radiothérapie , Tumeurs du sein/chirurgie , Femelle , Humains , Mastectomie , Score de propension , Radiothérapie adjuvante , Études rétrospectivesRÉSUMÉ
The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol's PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m2 and vincristine 1.4 mg/m2/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m2/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3-4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6-150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6-118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2-141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.