Potential value of tumor stiffness and sE-cadherin in predicting the response to neoadjuvant therapy in HER2-positive breast cancers.

Background: This prospective study compared the diagnostic value of tumor stiffness and serum soluble E-cadherin (sE-cadherin) expression for predicting response to neoadjuvant therapy in HER2-positive breast cancers. Methods: 112 patients with early or locally advanced HER2-positive breast cancer were enrolled. Maximum stiffness (Emax), mean stiffness (Emean) and their relative changes were assessed at t0 and t2. sE-cadherin levels were analyzed using ELISA. Pathological complete response was defined as no invasive disease in the breast and axilla (ypT0/is, ypN0) after surgery. The ability of tumor stiffness, sE-cadherin and the combination of ΔEmean (the relative change in Emean after the second cycle of neoadjuvant therapy) and sE-cadherin in predicting tumor responses was assessed using receiver operating characteristic curves and the Z-test. Results: Tumor stiffness and sE-cadherin decreased during neoadjuvant therapy. ΔEmean and sE-cadherin revealed the best predictive performance, with areas under the curve (AUCs) of 0.843 and 0.857, respectively. No significant differences in AUCs were reported between ΔEmean and sE-cadherin (p = 0.795). The combined use of ΔEmean and sE-cadherin showed the highest sensitivity and specificity (93.22 and 90.57%, respectively), with an AUC of 0.937. Conclusion: The combination of ΔEmean and sE-cadherin may improve the predictive power of each single factor. Although further verification is required, this study may promote noninvasive prediction of neoadjuvant therapy responses and help personalize the treatment regimen.

HER2 positivity in breast cancer is associated with a poor prognosis and shortened overall survival. For patients with HER2-positive early breast cancer, the standard neoadjuvant treatment consists of trastuzumab and pertuzumab plus docetaxel, and produces high response rates. In spite of the success of neoadjuvant therapy, some patients show no response due to drug resistance. An accurate prediction of the response of early HER2-positive breast cancer to neoadjuvant therapy would allow the modification of treatment with a response-guided strategy, thereby improving overall survival. Shear wave elastography and serum soluble E-cadherin may provide useful data on responsiveness to neoadjuvant therapy in breast cancers. This study was conducted to compare the diagnostic value of tumor stiffness and soluble E-cadherin expression for predicting the response to neoadjuvant therapy in HER2-positive breast cancers. Although these results will require further verification with larger studies, this study may promote noninvasive prediction of neoadjuvant therapy responses and help personalize the treatment regimen.

Augmentation Method for High Intra-Class Variation Data in Apple Detection.

Deep learning is widely used in modern orchard production for various inspection missions, which helps improve the efficiency of orchard operations. In the mission of visual detection during fruit picking, most current lightweight detection models are not yet effective enough to detect multi-type occlusion targets, severely affecting automated fruit-picking efficiency. This study addresses this problem by proposing the pioneering design of a multi-type occlusion apple dataset and an augmentation method of data balance. We divided apple occlusion into eight types and used the proposed method to balance the number of annotation boxes for multi-type occlusion apple targets. Finally, a validation experiment was carried out using five popular lightweight object detection models: yolox-s, yolov5-s, yolov4-s, yolov3-tiny, and efficidentdet-d0. The results show that, using the proposed augmentation method, the average detection precision of the five popular lightweight object detection models improved significantly. Specifically, the precision increased from 0.894 to 0.974, recall increased from 0.845 to 0.972, and mAP0.5 increased from 0.982 to 0.919 for yolox-s. This implies that the proposed augmentation method shows great potential for different fruit detection missions in future orchard applications.

Systematic review and meta-analysis of totally laparoscopic versus laparoscopic assisted distal gastrectomy for gastric cancer.

BACKGROUND: Totally laparoscopic distal gastrectomy (TLDG) has been developed in the hope of improving surgical quality and overcoming the limitations of conventional laparoscopic assisted distal gastrectomy (LADG) for gastric cancer. The aim of this study was to determine the extent of evidence in support of these ideals. METHODS: A systematic review of the two operation types (LADG and TLDG) was carried out to evaluate short-term outcomes including duration of operation, retrieved lymph nodes, estimated blood loss, resection margin status, technical postoperative complications, and hospital stay. RESULTS: Twelve non-randomized observational clinical studies involving 2,255 patients satisfied the eligibility criteria. Operative time was not statistically different between groups (P > 0.05). The number of retrieved lymph nodes and the resection margin length in TLDG were comparable with those in LADG. Estimated blood loss was significantly less in TLDG than that in LAG (P < 0.01). Compared to LADG, TLDG also involved lesser postoperative hospital stay (P < 0.01) and earlier time to soft diet intake (P < 0.05). Time to flatus and postoperative complications were similar for those two operative approaches. CONCLUSIONS: TLDG may be a technically safe, feasible, and favorable approach in terms of better cosmesis, less blood loss, and faster recovery compared with LADG.

Targeting CXCL12-CXCR4 Signaling Enhances Immune Checkpoint Blockade Therapy Against Triple Negative Breast Cancer.

Insufficient T cell infiltration in triple-negative breast cancer (TNBC) has limited its response rate to immune checkpoint blockade (ICB) therapies and motivated the development of immunostimulatory approaches to enhance the ICB therapy. CXCR4 is a chemokine receptor highly upregulated both on cell surface and cytoplasm in tumor tissues. Activating CXCR4 has been associated with increased immunosuppression in the tumor microenvironment. Here, we developed a CXCR4-targeted liposomal formulation (Liposomal-AMD3100) to enhance therapeutic efficacy of AMD3100, a CXCR4 antagonist. Particularly, AMD3100 is not only encapsulated into the liposome but coated on the surface of the formulation to serve as a targeting moiety and a dual blocker capable of inhibiting CXCR4 activation extracellularly and intracellularly. The Liposomal-AMD3100 remodeled both immune and stromal microenvironment more efficiently compared with free AMD3100, indicating better pharmacodynamic profile of AMD3100 achieved by liposomal formulation. The combination of anti-PD-L1 with Liposomal-AMD3100 formulation exhibited an increased antitumor effect and prolonged survival time compared with monotherapies in a murine TNBC model (4T1). This work proves that immune activation via liposomal delivery of CXCR4 inhibitors has a great potential to expand ICB therapies to originally ICB-insensitive cancer types.

Coexpression of PBX1 and EMP2 as Prognostic Biomarkers in Estrogen Receptor-Negative Breast Cancer via Data Mining.

Previous studies revealed that PBX1 ranked the third in the differentially expressed genes about development and progression of breast cancer (BC). Nevertheless, the role of PBX1 contributing to progression of BC has been unevaluated. Here, on the basis of ONCOMINE and GOBO databases, we compared BC samples with normal controls about the expression of PBX1 in various types of cancers, as well as their related expression levels in cancer cell lines by Cancer Cell Line Encyclopedia (CCLE) analysis. It was also found that, when compared with normal controls, PBX1 was markedly higher expressed not only in BC samples but also in BC cell lines, and coexpressed with EMP2 by ONCOMINE and CCLE coexpression analysis, which was also expressed higher in BC samples and BC cell lines similarly. According to Kaplan-Meier plotter, we further explored the prognostic functions of PBX1 and EMP2 in different molecular subtypes of BC, respectively. We demonstrated that overexpression of PBX1 mRNA was correlated with worse survival in luminal B subtype BC, whereas increased EMP2 expression was associated with shorter relapse-free survival in estrogen receptor (ER)-negative patients. Combining with previous studies, we could make a conclusion that coexpression of PBX1 and EMP2 predicts poor prognosis in ER-negative BC, which could be effective biomarkers for BC.

Usefulness of postoperative serum translocator protein as a predictive marker for delirium after breast cancer surgery in elderly women.

OBJECTIVE: Postoperative delirium (POD) has rarely been investigated in breast cancer patients. Herein, we assessed the association between serum levels of the inflammatory biomarker translocator protein (TP) and the occurrence of POD in breast cancer patients. METHODS: In this prospective, observational study, TP levels were detected in preoperative and postoperative serum samples from 152 elderly breast cancer patients, samples from 152 healthy elderly women, and samples from 152 elderly women with benign breast diseases. The relationship between serum TP levels and POD was investigated using multivariate analysis. RESULTS: TP levels in postoperative patient serum samples were significantly higher than in preoperative patient serum samples and serum from women in the two control groups. Postoperative serum TP levels were independently correlated with serum C-reactive protein levels and the occurrence of POD. Postoperative serum TP levels had a high discriminatory ability for POD under the receiver operating characteristic curve. CONCLUSIONS: Increased postoperative serum TP levels are independently associated with the degree of inflammatory response and the risk of POD in elderly breast cancer patients, substantializing TP as an inflammatory biomarker that can efficiently discriminate POD after breast cancer surgery.

Predictive value of serum cyclophilin A concentrations after acute pancreatitis.

BACKGROUND: Cyclophilin A is identified as a biomarker for inflammation. We elucidated prognostic significance of serum cyclophilin A (CypA) concentrations in acute pancreatitis (AP). METHODS: In this prospective and observational study, serum CypA concentrations were quantified in 210 AP patients and 100 healthy controls. We recorded local complication, in-hospital mortality and organ failure. Disease severity was assessed using the traditional predictors, namely Acute Physiology and Chronic Health Care Evaluation II score, Ranson score, multiple organ dysfunction score and sequential organ failure assessment score. RESULTS: Serum CypA concentrations were significantly lower in controls than in AP group. CypA concentrations after AP were highly correlated with the traditional predictors and other inflammatory mediators, including blood erythrocyte sedimentation rate, procalcitonin levels, white blood cell count and C-reactive protein levels. Serum CypA emerged as an independent predictor for in-hospital local complication, organ failure and mortality. Under receiver operating characteristic curve, serum CypA possessed similar prognostic ability, as compared to the traditional predictors. Its predictive ability was almost similar to that of procalcitonin levels and significantly exceeded those of the other inflammatory mediators. Also, it significantly improved prognostic performance of the traditional predictors. CONCLUSIONS: Increased serum CypA concentrations have close relation to the severity, inflammation and prognosis, substantializing CypA as a potential prognostic biomarker of AP.

Candidate microRNAs as biomarkers of thyroid carcinoma: a systematic review, meta-analysis, and experimental validation.

Thyroid cancer is one of the most common carcinomas of the endocrine system with an increasing incidence. A growing number of studies have focused on the diagnostic and prognostic values of dysregulated microRNAs (miRNAs) in thyroid carcinoma. However, differences in the measurement platforms, variations in lab protocols, and small sample sizes can make gene profiling data incomparable. A meta-review of the published studies that compared miRNA expression data of thyroid carcinoma and paired normal tissues was performed to identify potential miRNA biomarkers of thyroid carcinoma with the vote-counting strategy. Two hundred and thirty-six aberrantly expressed miRNAs were reported in 19 microRNA expression profiling studies. Among them, 138 miRNAs were reported in at least two studies. We also provided a meta-signature of differentially expressed miRNAs between individual histological types of thyroid carcinoma and normal tissues. The experimental validation with qRT-PCR analysis verified that the profiles identified with the meta-review approach could effectively discriminate papillary thyroid carcinoma tissues from paired noncancer tissues. The meta-review of miRNA expression profiling studies of thyroid carcinoma would provide information on candidate miRNAs that could potentially be used as biomarkers in thyroid carcinoma.

Elevated plasma visfatin levels correlate with poor prognosis of gastric cancer patients.

Visfatin is a proinflammmatory cytokine with accumulating evidence for its rise in circulation of cancer patients. This study aimed to evaluate the relationship between preoperative plasma visfatin level and prognosis of gastric cancers. Preoperative plasma visfatin levels of 262 patients with gastric cancers and plasma visfatin levels of 262 healthy individuals were determined using enzyme-linked immunosorbent assay. Preoperative plasma visfatin level was substantially higher in patients than in healthy subjects. Plasma visfatin levels were associated with invasion depth, lymph node metastasis, distant metastasis, peritoneal dissemination, tumor size and tumor node metastasis stage. Multivariate analysis revealed that high plasma visfatin level was an independent factor for death. Receiver operating characteristic curve analysis showed that plasma visfatin level predicted death with high area under curve. Multivariate Cox regression analysis identified plasma visfatin level as an independent predictor of overall survival. Thus, our results suggest that high preoperative plasma visfatin level is associated with prognostic factors for gastric cancer as well as may play a role as prognostic biomarker in gastric cancer survival.