Inclusion complexes of ß-cyclodextrin with isomeric ester aroma compounds: Preparation, characterization, mechanism study, and controlled release.

Cyclodextrins (CDs) have been discovered to provide an efficient solution to the limited application of ester aroma molecules used in food, tobacco, and medication due to their strong smell and unstable storage. This work combined molecular modeling and experimental to analyze the conformation and controlled release of isomeric ester aroma compounds/ß-CD inclusion complexes (ICs). The investigation revealed that ester aroma compounds could be effectively encapsulated within the ß-CD cavity, forming ICs with low binding affinity. Furthermore, the key driving forces in ICs were identified as hydrogen bonds and van der Waals interactions through theoretical simulation. Results from the Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and Isothermal titration calorimetry (ITC) experiments confirmed the intermolecular interaction predicted by the molecular model. Notably, the release rate of aroma compounds from L-menthyl acetate/ß-CD (LMA/ß-CD) IC exceeded that of terpinyl acetate/ß-CD (TA/ß-CD) IC. This difference is attributed to the length of the chain of aroma molecules and the variation in the position of functional groups, influencing the stable formation of ICs with ß-CD. These findings hold potential implications for refining the application of ICs across diverse industries.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

Research progress of starch as microencapsulated wall material.

Starch is non-toxic, low cost, and possesses good biocompatibility and biodegradability. As a natural polymer material, starch is an ideal choice for microcapsule wall materials. Starch-based microcapsules have a wide range of applications and application prospects in fields such as food, pharmaceuticals, cosmetics, and others. This paper firstly reviews the commonly used wall materials and preparation methods of starch-based microcapsules. Then the effect of starch wall materials on microcapsule properties is introduced in detail. It is expected to provide researchers with design inspiration and ideas for the development of starch-based microcapsules. Next the applications of starch-based microcapsules in various fields are presented. Finally, the future trends of starch-based microcapsules are discussed. Molecular simulation, green chemistry, and solutions to the main problems faced by resistant starch microcapsules may be the future research trends of starch-based microcapsules.

Recent advances of magnetic chitosan hydrogel: Preparation, properties and applications.

Magnetic chitosan hydrogels are organic-inorganic composite material with the characteristics of both magnetic materials and natural polysaccharides. Due to its biocompatibility, low toxicity and biodegradability, chitosan, a natural polymer has been widely used for preparing magnetic hydrogels. The addition of magnetic nanoparticles to chitosan hydrogels not only improves their mechanical strength, but also endows them with magnetic thermal effects, targeting capabilities, magnetically-sensitive release characteristics, easy separation and recovery, thus enabling them to be used in various applications including drug delivery, magnetic resonance imaging, magnetothermal therapy, and adsorption of heavy metals and dyes. In this review, the physical and chemical crosslinking methods of chitosan hydrogels and the methods for binding magnetic nanoparticles in hydrogel networks are first introduced. Subsequently, the properties of magnetic chitosan hydrogels were summarized including mechanical properties, self-healing, pH responsiveness and properties in magnetic fields. Finally, the potential for further technological and applicative advancements of magnetic chitosan hydrogels is discussed.

The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma.

BACKGROUND: The classification of thymomas is based on the morphology of epithelial tumor cells and the proportion of lymphocytes. Type A thymomas are composed of the spindle or oval tumor epithelial cells. Tumor cells of B thymomas are epithelioid-shaped with increasing atypia. Type AB thymomas have the features of epithelial tumor cells of A and B thymomas. The diagnosis can be difficult because of the complex morphology. Some novel thymic epithelial markers have been reported in several preclinical studies, but they have not been applied to clinical practice. Here, we investigated the expression of 3 cortical and 3 medullary markers, which are thymoproteasome-specific subunit ß5t (ß5t), thymus-specific serine protease 16 (PRSS16), cathepsin V, autoimmune regulator (AIRE), CD40 and claudin-4. METHODS: Immunohistochemistry was used to analyze 53 cases of thymomas and thymic squamous cell carcinomas (TSCC), aiming to explore the expression of cortical and medullary epithelial markers and their correlation with histological classification, Masaoka-Koga stage, and prognosis. RESULTS: Our results found that for cortical epithelial markers the expression of ß5t, PRSS16, and cathepsin V was higher in type AB and B thymomas than in micronodular thymoma with lymphoid stroma (MNT), and we observed a dramatic increase of ß5t and PRSS16 expression in type AB compared to type A thymomas. In medullary epithelial markers, the expression of AIRE was higher in type A than in B3 thymomas. CD40 and ß5t expression were associated with the Masaoka-Koga stage. High cathepsin V expression was related to a good prognosis and a longer progression-free survival. CONCLUSION: This is the first comprehensive analysis of the role of thymic cortical and medullary epithelial markers as biomarkers for differential diagnosis and prognosis in thymic tumors. Thymic medullary epithelial immunophenotype was found to exhibit in type A, MNT, and TSCC. Type B thymomas primarily exhibited a cortical epithelial immunophenotype. Type AB thymomas showed cortical, medullary, or mixed corticomedullary epithelial immunophenotype. Our results demonstrated that thymic cortical and medullary epithelial markers including ß5t, PRSS16, cathepsin V, and AIRE could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.

Benign but fatal: management of endotracheal Rosai-Dorfman disease with acute onset.

Rosai-Dorfman disease (RDD) is a non-malignant condition mainly manifesting as a proliferation of histiocytes in lymph nodes. Endotracheal RDD (ERDD) with an acute onset presentation is extremely rare. There are few case reports of ERDD mainly concerning its pathology, diagnostics and bronchoscopic treatment, without providing sufficient clinical information from a comprehensive perspective. As a novel and challenging technique, tracheal resection and reconstruction (TRR) with spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) has been reported as feasible and safe in highly selected patients, but few centres have shared their experience with this approach. This case-based discussion includes not only practical issues in the management of a life-threatening ERDD patient, but also specialists' views on the management of acute obstructive airway, and the surgeons' reflection on TRR with SV-VATS.

Malignant Mixed Epithelial and Stromal Tumor of the Kidney: Report of a Carcinosarcoma Case and an Updated Literature Review.

Mixed epithelial and stromal tumors of the kidney (MESTK) are rare and recently defined entities that comprise both epithelial and stromal cells. MESTK is mostly benign; however, to date, 18 borderline or malignant cases have been reported. In this study, we report a case of carcinosarcoma exhibiting a large carcinoma and small sarcoma component, and review the relevant literature. The patient was a 59-year-old woman who presented with a large mass in the left kidney having solid and focal cystic components. The patient underwent left radical nephrectomy. The tumor was gray-white and solid-cystic, with a relatively clear boundary. Microscopically, the tumor revealed benign and malignant components. The benign component consisted of multiple tubules, variable-sized cysts lined with benign epithelium, and hyalinized stroma. The malignant component was composed of predominantly small cell neuroendocrine carcinoma and a small quantity of adenocarcinoma, squamous cell carcinoma, and sarcoma. Finally, a diagnosis of the malignant MESTK was made. Certain cases of borderline or malignant transformation of MESTK have been published, so it is important to enhance findings made by other studies.

Silva cumulative score and its relationship with prognosis in Endocervical adenocarcinoma.

BACKGROUND: The Silva system has been demonstrated to have a good predictive value of lymph node metastasis (LNM) in endocervical adenocarcinoma (EAC). Tumours were classified based on the highest identified pattern of invasion in this system, this may not exactly reflect the true situation when it presents with a "mixed pattern" in some cases. Recent study has shown that patients with lymphovascular invasion (LVI) have worse prognosis in EAC. Here we design a Silva cumulative score (SCS) system which also combined the LVI status to explore its prognostic role in EAC patients. METHODS: A total of 120 patients with EAC were included in this study. Clinicopathological characteristics were retrospectively retrieved from the medical records and follow-up data were obtained. The clinicopathological information included age at diagnosis, depth of invasion (DOI), LNM, LVI, Silva classification, and SCS. SCS is a classification system based on the sum score of different Silva pattern which is founded on morphological phenomena. The relationships between the pathological characteristics and prognoses were analyzed. RESULTS: According to the Silva system, 11 (9.2%), 22 (18.3%) and 87 (72.5%) patients had patterns A, B, and C, respectively. Patients with pattern C had the highest incidence of LVI and LNM (p < 0.05). Although the Kaplan-Meier curves demonstrated that survival decreased with increasing Silva classification for A-C cancers, there was no statistically significant difference [disease-free survival (DFS): p = 0.181; overall survival (OS): p = 0.205]. There were 45 cases presented as mixed-type of Silva patterns. According to the SCS, 23 cases (19.2%) were rated as grade I, 31 cases (25.8%) as grade II and 66 (55.0%) cases as grade III. Patients with SCS grade III had the highest incidence of LVI and LNM (p < 0.05). Kaplan-Meier analysis revealed that patients with higher SCS had significantly shorter DFS and OS than those with lower SCS (p < 0.05). High SCS was an independent predictor of poorer OS and DFS (p < 0.05) in patients with EAC. CONCLUSIONS: The application of the Silva system could effectively predict the LNM of patients and may be helpful in selecting an appropriate surgical procedure. The SCS system we designed showed a good predictive value for DFS and OS in EAC.

Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor.

Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in-depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

Stimulus responsive microcapsules and their aromatic applications.

Fragrances and essential oils are promising for a wide range of applications due to their pleasant odors and diverse effects. However, direct addition to consumer products has the disadvantages of short retention time and easy deterioration of odor. At the same time, releasing a large amount of odor in a short time may be an unpleasant experience, which severely limits the practical application of aromatic substances. Microencapsulation perfectly solves these problems. Stimuli-responsive microcapsules, which combine environmental stimulation with microencapsulation, can not only effectively prevent the rapid decomposition and evaporation of aroma components, but also realize the "on-off" intelligent release of aroma substances to environmental changes, which have great promise in the field of fragrances. In this review, the application of stimuli-responsive microcapsules in fragrances is highlighted. Firstly, various encapsulation materials used to prepare stimuli-responsive aromatic microcapsules are described, mainly including some natural polymers, synthetic polymers, and inorganic materials. Subsequently, there is a detailed description of the common release mechanisms of stimuli-responsive aromatic microcapsules are described in detail. Finally, the application and future research directions are given for stimuli-responsive aromatic microcapsules in new textiles, food, paper, and leather.

Giant nodular fasciitis originating from the humeral periosteum: A case report.

BACKGROUND: Nodular fasciitis (NF) is a self-limiting tumor that mostly occurs in the subcutaneous superficial fascia. NF originating from the appendicular periosteum is extremely rare. A large NF lesion of periosteal origin can be misdiagnosed as a malignant bone tumor and may cause overtreatment. CASE SUMMARY: A right axillary mass was found in a 46-year-old man and was initially diagnosed intraoperatively as low-grade sarcoma, but later diagnosed as NF after post-resection histopathological evaluation. Furthermore, fluorescence in situ hybridization analysis revealed a USP6 gene rearrangement that confirmed the diagnosis. To the best of our knowledge, this is the first case of NF in the humeral periosteum. CONCLUSION: NF poses a diagnostic challenge as it is often mistaken for sarcoma. Postoperative histopathological examination of whole sections can be combined with immunohistochemical staining and, if necessary, the diagnosis can be confirmed by molecular detection, and thus help avoid overtreatment.

microRNA-200c-3p suppresses proliferation and invasion of nephroblastoma cells by targeting EP300 and inactivating the AKT/FOXO1/p27 pathway.

miR-200c-3p is aberrantly expressed in numerous cancers, but its underlying mechanisms in nephroblastoma are unknown. In our study, the differentially regulated miRNAs between the nephroblastoma tissues and adjacent non-neoplastic renal tissues were screened based on microarray analysis. The miR-200c-3p expression in nephroblastoma tissues and cells was detected by qRT-PCR. Then, the effects of miR-200c-3p mimic or inhibitor on cell proliferation, invasion, and migration were evaluated by CCK-8 assay, plate colony formation assay, soft agar assay, Transwell, and wound-healing assay in SK-NEP-1 and G401 cells. Afterward, the target gene of miR-200c-3p was predicted by TarBase, miRTarBase, miRDB softwares, and then verified by dual-luciferase reporter gene assay. The in vivo effects of miR-200c-3p on pathological changes and tumor volume were investigated in tumor xenograft mice by H&E staining and in vivo fluorescence imaging. ChIP assay was used to evaluate the relationship between histone acetyltransferase E1A-binding protein p300 (EP300) and P27, and the relationship of the role of miR-200c-3p in nephroblastoma and the AKT/FOXO1/p27 signaling pathways was evaluated by western blotting. Our study shows that miR-200c-3p was downregulated in nephroblastoma tissues and cells, and EP300 was a target gene of miR-200c-3p. Furthermore, miR-200c-3p mimic decreased cell proliferation and inhibited cell migration and invasion in nephroblastoma. Mechanistically, miR-200c-3p could inhibit p-AKT activity and enhance p-FOXO1 and p27 expression. Notably, the transcription factor P27 could bind to the EP300 promoter. This study demonstrates a new approach to treat nephroblastoma.

Ubiquitin C-terminal hydrolase-L1 expression in non-small-cell lung cancer and its association with clinicopathological features and prognosis.

UbiquitinC-terminal hydrolase-L1 (UCH-L1) is a cysteine hydrolase. It functions as a ubiquitin hydrolase, stabilizes the ubiquitin monomer, and affects cell division through cell cycle protein deubiquitination. Abnormal UCH-L1 expression is closely related to the occurrence and development of several tumors. Although some in vitro studies have demonstrated the significance of UCH-L1 in non-small-cell lung cancer (NSCLC), only few clinical studies have focused on the UCH-L1 expression in NSCLC, and the results are controversial and non-uniform. We investigated the UCH-L1 expression in 401 cases of surgically resected NSCLC, including 286 cases of adenocarcinoma (ADC) and 65 cases of squamous cell carcinoma. The associations between the UCH-L1 expression and clinicopathological features, programmed cell death-ligand 1 (PD-L1) expression, and prognostic significance were analyzed. For NSCLC, the UCH-L1 expression is associated with sex, smoking history, tumor size (>3 cm), lymphocyte infiltration, advanced pathological stages, and shortened overall survival (OS; 89.72 vs. 114.55 months; P = 0.005), but not PD-L1 expression. The UCH-L1 expression in ADC is associated with advanced pathological stages, pleural invasion, and shortened OS (90.38 vs. 118.55 months; P = 0.010). Multivariate analysis confirmed that UCH-L1 expression was an independent poor prognostic factor for NSCLC (OS: hazard ratio [HR], 1.854; 95% confidence interval [CI], 1.132-3.038; P = 0.014). Our results suggest that the UCH-L1 expression differs across tumors with different clinicopathological features, and it is related to poor prognosis.

Histopathologic features from preoperative biopsies to predict spread through air spaces in early-stage lung adenocarcinoma: a retrospective study.

BACKGROUND: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent. METHODS: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically. RESULTS: The study participants had a mean age of 59 years (range, 35-81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P <  0.001), necrotic/tumor debris (31 of 42; 73.8%; P <  0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P <  0.001), desmoplasia (35 of 41; 85.4%; P <  0.001), and grade 3 nuclei (12 of 14; 85.7%; P <  0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS. CONCLUSIONS: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.

PD-L1 expression and immune stromal features in HPV-independent cervical adenocarcinoma.

AIMS: Human papilloma virus (HPV)-independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD-1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD-ligand 1 (PD-L1). However, no data regarding PD-L1 expression in HPV-independent CA are available. Thus, we evaluated the association between PD-L1 expression and the clinicopathological characteristics and survival of patients with HPV-independent CA. METHODS: We evaluated PD-L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV-independent CA. PD-L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%. RESULTS: PD-L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD-L1 expression, based on either the CPS or the TPS, was associated with a high tumour-infiltrating lymphocyte percentage (CPS = P < 0.001; TPS = P < 0.001). Patients with a PD-L1 CPS ≥1 showed worse progression-free survival and overall survival than PD-L1-negative patients (P = 0.004 and P = 0.023, respectively). Forty-two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. CONCLUSIONS: Our data demonstrated that PD-L1 was expressed in HPV-independent CA, especially in clear cell carcinoma, and that PD-L1 expression is a negative prognostic marker. Our data support the role of PD-L1 in HPV-independent CA and its potential as an immunotherapeutic target.

A large real-world cohort study of examined lymph node standards for adequate nodal staging in early non-small cell lung cancer.

BACKGROUND: The current National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer (NSCLC) recommend that surgeons sample is not clear. We aimed to define a minimal number of examined lymph nodes for removal or sampling for optimized nodal staging recommendation, with a focus on T1-3N0M0 patients. METHODS: A total of 55,101 consecutive patients were selected, including 52,099 patients with US Surveillance, Epidemiology, and End Results (SEER) data and 3,002 patients in a Chinese multicenter database from 11 thoracic referral centers, who underwent complete resection plus lymph node dissection or sampling for stage T1-3N0M0 NSCLC. Propensity score-matching analysis was performed with R software, and a cut-off value was calculated using X-tile software. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: Five-year survival rates with respect to total examined lymph nodes numbers (examined lymph nodes <10 vs. examined lymph nodes ≥10) were 69% and 64% (group A), 66% and 63% (group B), 62% and 58% (group C), 81% and 75% (group D). There were significant differences between examined lymph nodes <10 and examined lymph nodes >10 in each group (P<0.001). CONCLUSIONS: A minimum of 10 examined lymph nodes would significantly improve T1-3N0M0 NSCLC prognosis and patients' survival rates if implemented as a minimum standard for lymphadenectomy. Therefore, we recommended a minimum of 10 examined lymph nodes for T1-3N0M0 patients.

Diagnostic Challenge of Sarcomatoid Variant of ALK-Positive Anaplastic Large Cell Lymphoma: Case Report and Updated Systematic Literature Review.

The sarcomatoid variant of anaplastic large cell lymphoma is an extremely rare histologic pattern of anaplastic large cell lymphoma that consists of spindle-shaped neoplastic cells and is easily misdiagnosed as a soft tissue sarcoma. We report a case of the sarcomatoid variant of anaplastic large cell lymphoma that was initially diagnosed as an inflammatory myofibroblastic tumor in our hospital and as liposarcoma after consultation. This article analyzed the features of this entity by reviewing the literature. Only 15 cases have been reported, most of which were misdiagnosed as sarcoma, sarcomatoid carcinoma, or inflammatory myofibroblastic tumor. Most of the reported cases showed a myxoid stroma, with a variable number of inflammatory cells. The hallmark cells usually can be found by careful evaluation of the slides. Immunohistochemistry including CD30, EMA, and ALK are the most useful for diagnosis. Most are III or IV stage, and have a good prognosis after chemotherapy.

A standard for hilar and intrapulmonary lymph node dissection and pathological examination in early non-small cell lung cancer.

BACKGROUND: There is considerable variation in the staging of lymph nodes (LNs) as part of tumor, node, metastasis (TNM) staging of non-small cell lung cancer (NSCLC). A new dissection and pathological examination standard for hilar and intrapulmonary LNs needs to be established for patients with early-stage T1-3N0M0 NSCLC. METHODS: This study involved 3,002 patients with T1-3N0M0 NSCLC who underwent radical lobectomy or total pneumonectomy in the thoracic departments of 11 Chinese institutions between January 1999 and October 2013. The Cox model was applied for univariate and multivariate analyses in the examination of station 10, 11 LN and station 12, 13, 14 LN. A hilar and intrapulmonary standard (HI standard) was then established based on univariate and multiple-factor analyses conducted using the Cox model. RESULTS: Among the 3,002 patients enrolled in the study, 2,609 underwent at least one examination of station 10, 11 LN (A1), while 393 did not undergo examination of station 10, 11 LN (A0). The A0 and A1 groups had 5-year survival rates of 76% and 80%, respectively (P=0.018). Further, 1,764 patients underwent at least one examination of station 12, 13, 14 LN (B1), while 1,238 patients did not (B0). The B0 and B1 groups had 5-year survival rates of 77% and 82%, respectively (P=0.008). In total, 1,269 patients attained the HI standard (C1), and 1,733 did not (C0). The C0 and C1 groups had 5-year survival rates of 77% and 83%, respectively (P<0.001). CONCLUSIONS: The HI standard can improve both the prognosis and survival rates of patients with T1-3N0M0 NSCLC. This will provide important guidance for pulmonary LN dissection and pathological examination in NSCLC cases.

YAP increases response to Trastuzumab in HER2-positive Breast Cancer by enhancing P73-induced apoptosis.

The role of the Yes-associated protein (YAP) in oncogenesis and progression of breast cancer remains controversial. Meanwhile, development of therapeutic resistance to trastuzumab, a common breast cancer treatment administered after chemotherapy, is a significant challenge in the treatment of HER2-positive breast cancer. We, therefore, analyzed the role of YAP in trastuzumab resistance in HER2-positive-breast carcinoma cells in vitro and evaluated the status of YAP and related proteins in patient-derived breast carcinoma tissues by immunohistochemistry. YAP expression was observed in both BT474-TS (trastuzumab-sensitive) and BT474-TR (trastuzumab-resistant) cells. Treatment with trastuzumab increased expression of nuclear-YAP (N-YAP) in BT474-TS cells, whereas BT474-TR cells showed a decrease in N-YAP expression following trastuzumab treatment. YAP silencing significantly reduced trastuzumab-induced inhibitory effects in BT474-TS cells. YAP-silenced cells also showed decreased apoptosis and significantly lower p73 levels following trastuzumab treatment. Combined protein kinase B (AKT) inhibitor-trastuzumab treatment significantly inhibited BT474-TR cell proliferation, resulting in increased N-YAP and p73 expression, as well as apoptosis. In both paclitaxel, doxorubicin and cyclophosphamide (TAC)-treated, and docetaxel, carboplatin, and trastuzumab (TCbH)-treated groups; the pathological complete response (pCR) ratios were inversely correlated with p-AKT status in biopsy specimens, while YAP and p73 status were positively correlated with the pCR ratio in the biopsy specimens of the TCbH group. Our results show that YAP is involved in trastuzumab resistance in HER2-positive breast carcinoma cells and that YAP and AKT may be developed as prognostic markers of neoadjuvant trastuzumab therapy in patients with HER2-positive breast cancer.