Several patient-derived tumor models emerged recently as robust preclinical drug-testing platforms. However, their potential to guide clinical therapy remained unclear. Here, we report a model called patient-derived tumor-like cell clusters (PTCs). PTCs result from the self-assembly and proliferation of primary epithelial, fibroblast, and immune cells, which structurally and functionally recapitulate original tumors. PTCs enabled us to accomplish personalized drug testing within 2 weeks after obtaining the tumor samples. The defined culture conditions and drug concentrations in the PTC model facilitate its clinical application in precision oncology. PTC tests of 59 patients with gastric, colorectal, or breast cancers revealed an overall accuracy of 93% in predicting their clinical outcomes. We implemented PTC to guide chemotherapy selection for a patient with mucinous rectal adenocarcinoma who experienced recurrence with metastases after conventional therapy. After three cycles of a nonconventional therapy identified by the PTC, the patient showed a positive response. These findings need to be validated in larger clinical trials, but they suggest that the PTC model could be prospectively implemented in clinical decision-making for therapy selection.
Background: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). Methods: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0–3) at 90 days. We also performed a sensitivity analysis with the propensity score matching–based and the instrumental variable–based analysis. Results: In our primary analysis using the inversed probability of treatment weighting–based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19–1.65]; absolute risk difference, 11.8% [95% CI, 6.9–16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69–0.88]; absolute risk difference, −10.3% [95% CI, −15.8 to −4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching–based and instrumental variable–based analysis. Conclusions: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. Registration: URL: www.chictr.org.cn ; Unique identifier: ChiCTR2000041117.
BACKGROUND: Although traditional intraoperative assessments (ie, frozen sections) may lower reoperation rates in patients with breast cancer, time/tissue limitations and accuracy concerns have discouraged their routine clinical use. Full-field optical coherence tomography (FFOCT) and dynamic cell imaging (DCI) are novel optical imaging techniques offering rapid histologic approximations that are unfettered by requisite handling steps. This study was conducted to determine the feasibility and diagnostic utility of FFOCT and DCI in examining breast and lymph node specimens during breast cancer surgery. METHODS: FFOCT and DCI were applied to normal and cancerous breast tissue, benign breast lesions, and resected axillary lymph nodes. The tissues were then subjected to conventional processing and staining (hematoxylin-eosin) for purposes of comparison. RESULTS: A total of 314 specimens, including 173 breast biopsies (malignant, 132; benign/normal, 41) and 141 resected lymph nodes (tumor-positive, 48; tumor-negative, 93), were obtained from 158 patients during breast surgery for prospective imaging evaluations. In breast cancer diagnosis, the minimum sensitivities (FFOCT, 85.6%; DCI, 88.6%) and specificities of optical imaging (FFOCT, 85.4%; DCI, 95.1%) were high, although they diverged somewhat in nodal assessments (FFOCT sensitivity, 66.7%; FFOCT specificity, 79.6%; DCI sensitivity, 83.3%; DCI specificity, 98.9%). CONCLUSIONS: These timely and tissue-sparing optical imaging techniques proved highly accurate in diagnosing breast cancer and nodal metastasis. They compare favorably with routine histologic sections and demonstrate their promise in this setting.
Purpose This study aimed to assess the value of the combination of indocyanine green (ICG) and methylene blue (MB) dye in early breast cancer patients undergoing sentinel lymph node biopsy (SLNB).Methods Between January 2011 and December 2015, 1061 early breast cancer patients underwent SLNB were included. SLNB was performed for enrolled patients by injection of both ICG and MB. Detection rate, positivity, and number of sentinel lymph nodes (SLNs) by ICG and MB were analysed. Axillary recurrence and arm lymphedema at 5.6 years follow-up were reported.Results The combination of ICG and MB resulted in a very high detection rate of 99.6%, the median number of sentinel lymph nodes was 3. A total of 374 histologically con rmed positive SLNs were detected in 237 patients, 96.6% of the positive patients and 94.1% of the positive nodes could be identi ed by the combination of ICG and MB. After a median follow-up of 5.6 (2 to 9.3) years, 0.64% of patients with negative SLNs had ipsilateral axillary recurrence, and the incidence of arm lymphedema was 2.1%.Conclusions Although the missing isotope control weakens the interpretation of the ndings, the dual tracing modality of ICG and MB, without involvement of radioactive isotopes, was an effective method for SLNB in patients with early breast cancer.
Purpose: The dilemma of undertreatment and overtreatment of elderly breast cancer patients is common. This study aimed to investigate clinicopathological features, treatment modalities, and survival in women diagnosed with breast cancer at age 70 years or over, and to assist clinicians in developing individualized treatment plans by balancing the risks of breast cancer-specific death (BCSD) and other cause-specific death (OCSD).Methods: This retrospective study included 420 women who were diagnosed with pathologically confirmed invasive breast cancer at age 70 years or older from January 2008 to December 2015 at Peking University People's Hospital (PKUPH). We collected baseline health status, tumor characteristics, treatment choices, and outcomes and created nomograms for clinicians to estimate individualized BCSD and OCSD risk directly.Results: During a median follow-up of 71.5 months (range 2 to 144 months) in patients with stage I–III tumors, breast cancer specific survival (BCSS) was 92.4% (376/407) and overall survival (OS) was 78.1% (318/407). There were 89 deaths, and 65.2% (58/89) were non-breast cancer related. Upon multivariate analysis by Cox regression model, tumor size, positive lymph nodes, Ki-67, and surgery were independent predictors of BCSS, and comorbidities, positive lymph nodes, Ki-67, surgery, and endocrine therapy were independent predictors of OS. Propensity score weighted (PSW) was applied to analyze therapeutic efficacy, and there was BCSS and OS benefit with surgery (both p < 0.001), BCSS benefit with chemotherapy (p = 0.029), BCSS and OS benefit with endocrine therapy (p = 0.006 and 0.004), and neither BCSS nor OS benefit with radiotherapy (RT) (p = 0.348 and 0.289). Competing-risk nomograms were developed to estimate cumulative mortality probabilities for BCSD and OCSD for individual patients according to clinicopathologic characteristics and treatments. The calibration curves displayed exceptionally, with C-indexes 0.714 for BCSD and 0.717 for OCSD.Conclusions: Older patients had greater risk of dying from non-breast cancer causes. Surgery, chemotherapy, and endocrine therapy were associated with improved survival. Competing risk nomograms allowed individual assessment of BCSD and OCSD, based on clinicopathological characteristics and treatment options, and can be used as a tool to help in choosing appropriate treatment strategies.This study was approved by the Peking University People's Hospital Research Ethics Board on September 4, 2018.
The ring-shaped cohesin complex is an important factor regulating genome structure. It is thought to mediate the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we directly visualized cohesin loading after up-regulation of cohesin subunit Rad21 by identifying the formation of vermicelli-like structures via live cell super-resolution imaging. We also reveal that cohesin loading can be promoted by Rad21-loader interactions and accumulated contacts were shown at TAD corners while inter-TAD interactions increased after vermicelli formation, indicating that Rad21 is an important determinant of chromatin structure. Moreover, we find that cohesin saddle on topologically associating domains by FISH assay, which is consistent with the CTCF/cohesin-anchored chromatin loop model. Importantly, expression of Rad21 is strictly controlled, and aberrant expression of Rad21 leads to the formation of Rad21 “beads” in the nucleus. In summary, our observations provided important new biological insights into the mechanism of cohesin loading and its functions.
Ultrasound diagnosis of axillary lymph nodes has the advantages of ease, convenience and low cost; however, most previous studies evaluated lymph node metastasis of the entire axilla rather than the association between the ultrasound features of a single lymph node and its pathology. This prospective study was performed to explore the ultrasound features of lymph nodes observed in bionic medium in vitro and to develop a lymph node-specific model for prediction of metastasis based on analysis of the association between the ultrasound features and pathology of each lymph node.
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