A tumor immune microenvironment-related integrated signature can predict the pathological response and prognosis of esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy: A multicenter study in China.

BACKGROUND: Currently, there are insufficient indicators for the reliable assessment of treatment response following neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). Considering the essential role of protein-coding and non-coding RNAs in gene regulation and cellular processes, we systematically explored the molecular features and clinical significance of mRNA and lncRNA in 249 pretreatment biopsies from four hospitals in three districts with a high incidence of ESCC patients in China. METHODS: During the discovery phrase, 13 differentially expressed genes were identified and validated between samples with a complete pathological response (pCR) and those with an incomplete pathological response (

Clinicopathological observation of mature teratoma with malignant transformation, a single center retrospective study.

Purpose: To investigate the clinicopathological features of mature teratoma with malignant transformation. Methods: Retrospectively analysis of 1179 cases mature teratoma was done from August 1999 to December 2019 in Institution. 14 cases of mature teratoma with malignant transformation were discussed mainly for the pathological characteristics and clinical manifestations. Results: 4 of them were less than 40 years old. All but one occurred in the ovaries, and the one was in the left anterior mediastinum which was the only male. The clinical manifestations of the patients were atypical. Imaging showed cystic solid mass. Surgery was performed. Polypoid mass, solid nodule and thickened area of cyst wall can be seen on the section of tumor. Pathological results show that there were 5 cases of squamous cell carcinoma, 3 cases of carcinoid, 2 cases of serous carcinoma and 2 cases of thyroid papillary carcinoma, 1 case of carcinosarcoma and 1 case of strumal carcinoid. Two cases of squamous cell carcinoma had pelvic and abdominal metastasis. Immunohistochemistry of case 14 showed that AE1/AE3, CD56, SYN, NSE, PSAP, CDX2 were positive in carcinoid. EMA and CK20 were positive in mucinous glands around carcinoid. Calretinin and inhibin were positive in the mesenchyme adjacent to intestinal mucinous gland. Conclusions: Teratoma with malignant transformation is a rare malignancy, although teratoma is a common germ cell tumor. And it's more common in patients over 40 years, especially those patients who were in menopause. Squamous cell carcinoma is the most common type and prone to metastasis. Strumal carcinoid was well-defined, but as an endocrine tumor, it may cause a series of digestive, respiratory or hormonal disorders. Therefore, the mature teratomas should be removed in time after detection.

Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability.

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which have the worst prognosis and distant metastasis-free survival among breast cancer subtypes. Now, no targeted therapies are available for patients with BLBC due to the lack of reliable and effective molecular targets. Here, we performed the BLBC tissue microarray-based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. FGD5 deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells. Furthermore, genetic inhibition of Fgd5 in mouse mammary epithelial cells attenuated BLBC initiation and progression by reducing the self-renewal ability of tumor-initiating cells. In addition, FGD5 abundance was positively correlated with the abundance of epidermal growth factor receptor (EGFR) in BLBCs. FGD5 ablation decreased EGFR abundance by reducing EGFR stability in TNBC cells in 2D and 3D culture conditions. Mechanistically, FGD5 binds to EGFR and interferes with basal EGFR ubiquitination and degradation induced by the E3 ligase ITCH. Impaired EGFR degradation caused BLBC cell proliferation and promoted invasive properties and self-renewal. To verify the role of the FGD5-EGFR interaction in the regulation of EGFR stability, we screened a cell-penetrating α-helical peptide PER3 binding with FGD5 to disrupt the interaction. Treatment of BLBC patient-derived xenograft-bearing mice with the peptide PER3 disrupting the FGD5-EGFR interaction either with or without chemotherapy reduced BLBC progression. Our study identified FGD5 as a positive modulator of tumor-initiating cells and suggests a potential therapeutic option for the BLBC subtype of breast cancer.

TRIB3 promotes MYC-associated lymphoma development through suppression of UBE3B-mediated MYC degradation.

The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in MycEµ mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression.

A three-lncRNA signature of pretreatment biopsies predicts pathological response and outcome in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy.

BACKGROUND: Current strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population. METHODS: Differentially expressed lncRNAs (DELs) between pCRs and less than pCR (

Targeting PIN-1 Attenuates GCB DLBCL Cell Proliferation Through Inhibition of PI3K/AKT Signaling.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous type of non-Hodgkin lymphoma with many molecular subtypes that can be distinguished by gene expression profiling (GEP). However, the pathogenesis of DLBCL is still unclear. MATERIALS AND METHODS: The expression levels of the prolyl isomerase PIN-1 and other related proteins were determined in 73 primary DLBCL patient samples and cell lines by Western blotting (WB) and immunohistochemical (IHC) staining. Cell cycle and apoptosis were evaluated by flow cytometry. Lymphoma cell viability was detected by CCK-8 proliferation assay. RESULTS: High levels of PIN-1 expression were detected in 55% of germinal center B cell (GCB) DLBCL patient samples, whereas such abnormal expression levels were found in only 11% of non-GCB DLBCL patient samples. PIN-1 expression was positively associated with activation of the oncogenic phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in both GCB DLBCL cell lines and primary patient samples. Depletion of PIN-1 was cytotoxic to GCB DLBCL model cell lines because it led to inhibition of the PI3K/AKT signaling pathway, revealing a GCB DLBCL subgroup that is dependent on this pathway. A PI3K inhibitor was selectively toxic to GCB DLBCL lines expressing high levels of PIN-1. CONCLUSION: Our study used PIN-1 to identify a new subgroup of GCB DLBCL associated with the PI3K/AKT signaling pathway, and our findings reveal that inhibition of PI3K is a promising therapeutic approach for GCB DLBCL.

An individualized immune signature of pretreatment biopsies predicts pathological complete response to neoadjuvant chemoradiotherapy and outcomes in patients with esophageal squamous cell carcinoma.

No clinically available biomarkers can predict pathological complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) with neoadjuvant chemoradiotherapy (nCRT). Considering that antitumor immunity status is an important determinant for nCRT, we performed an integrative analysis of immune-related gene profiles from pretreatment biopsies and constructed the first individualized immune signature for pCR and outcome prediction of ESCCs through a multicenter analysis. During the discovery phase, 14 differentially expressed immune-related genes (DEIGs) with greater than a twofold change between pCRs and less than pCRs (

Single-channel UV/vis dual-band detection with ZnCdS:Mn/ZnS core/shell quantum dots.

In the ultraviolet detection system, the Si-based photodetector could be sensitised with different kinds of fluorescent material to enhance its response in the short-wavelength range. Thick-shell ZnCdS:Mn/ZnS core/shell quantum dots (QDs) exhibit unique advantages in UV signal sensitisation due to their long PL lifetime, as well as stable emission matched with CCD's response. Herein, a single-channel UV panoramic detection system based on these Mn-doped QDs has been proposed. The QDs@PMMA film was attached on a Si-based CCD camera versus a tapered fibre, and an optical chopper was mounted before the QDs@PMMA film. The long lifetime fluorescence originating from UV signal could be still collected by the CCD camera when the chopper is in the 'off' state, hence the UV/vis signal ratio is significantly enhanced.

Effect of surface/interfacial defects on photo-stability of thick-shell CdZnSeS/ZnS quantum dots.

High color-purity CdZnSeS alloy cores and CdZnSeS/ZnS core/shell quantum dots (QDs) with 3, 11 and 17 monolayer (ML) ZnS shells are synthesized, and the narrow emission (full-width at half-maximum: ∼21 nm) is ascribed to the high size uniformity of QDs and the narrow linewidth of single QD spectra. Ultraviolet (UV) irradiation experiments show that the photo-stabilities of the samples improve remarkably with increasing shell thickness, but the photo-stability clearly decreases when the shell thickness is further increased to 17 MLs. Spectroelectrochemical (SEC) measurements indicate that the exciton recombination of QDs is mainly affected by surface electronic traps, and the interaction between exciton recombination centers and surface traps is significantly weakened with the increase in shell thickness due to the decreased wave function overlap of the exciton and surface traps. In the case of the 17 ML shell, the reduced photo-stability is due to increased interfacial defects caused by stress release during UV illumination, which can be proved by high-resolution transmission electron microscopy images and X-ray diffraction patterns. Furthermore, based on QDs' theoretical mass calculations, a photo-stable white light-emitting diode is fabricated by encapsulating with a thick-shell QD, and an exceptional color gamut of 130% relative to the National Television Systems Committee color space can be achieved. Also, its colorimetry and photometry are discussed in detail.

A clinical analysis of 114 cases of sarcomatoid carcinoma of the lung.

The aim was to investigate the clinicopathological characteristics, diagnosis, and prognosis of sarcomatoid carcinoma of the lung. We reviewed 114 cases of sarcomatoid carcinoma of the lung in patients that were admitted to the First Affiliated Hospital of Zhengzhou University and Anyang Tumor Hospital from January 2009 to March 2018. We analyzed the clinical characteristics, immunohistochemical profiles, treatments, and overall survival of the patients. The patient population included 88 men and 26 women. Median patient age was 65 years (range 37-88 years), and the gender ratio (M/F) was 3.4:1. Median survival was 3.5 months (range 0.5-60 months). Univariate analysis showed that tumor location, tumor size, M stage, TNM stage, chemotherapy, and surgery were all prognostic factors for survival (P < 0.05). We found that T stage, surgery, and chemotherapy were independent prognostic factors for sarcomatoid carcinoma (P < 0.05). Pulmonary sarcomatoid carcinoma is a rare tumor with a poor prognosis. Patients with smaller T stage, complete resection, and chemotherapy exhibited a better prognosis. Early diagnosis and early treatment are important to improve the prognosis of these patients.

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5.

BACKGROUND/AIMS: MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer. METHODS: In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo. RESULTS: In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis. CONCLUSION: These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.

"Giant" quantum dots encapsulated inside a freeform lens.

A freeform lens containing giant red and green quantum dots (QDs) was designed to be used for a direct-illumination-type LED backlight wide-color-gamut display. Encapsulating the QDs with the freeform lens enabled us to not only expand the illumination area, where the uniform lighting area was about 2 cm in radius on the plane 1.5 cm above the LED, but to also avoid QDs coming into direct contact with the LED chip, which reduced the QDs' surrounding temperature from 94°C to 61°C. Moreover, this encapsulation and the thick shell of the QDs significantly improved the device's lifetime up to more than 100 h due to the reduced temperature. A color gamut of ∼130% of the National Television Systems Committee standard was obtained with the freeform lens.

Increased Jab1/COPS5 is associated with therapeutic response and adverse outcome in lung cancer and breast cancer patients.

Adjuvant chemotherapy has been established as standard treatment for advanced cancer among multidisciplinary therapies. A simple and instructive biomarker for therapeutic response and recurrence is needed to evaluate the therapeutic effect. Jab1/COPS5 level has been shown to be associated with tumor progression and poor outcomes in many types of cancer patients. This study aims to further evaluate the clinical and prognostic value of Jab1/COPS5 level as a biomarker in lung and breast cancer patients receiving adjuvant chemotherapy. In this study, data of 88 lung cancer and 76 breast cancer patients were retrospectively collected and analyzed to identify the relationship between the Jab1/COPS5 level and the clinical progression and outcome of these patients. Lung cancer patients with increased Jab1/COPS5 level tend to be non-responsive to chemotherapy. Relapsed breast cancer patients had an increased Jab1/COPS5 level and breast cancer patients with increased Jab1/COPS5 level had significantly shorter disease-free survival and overall survival. In a multivariate survival analysis, histological type and Jab1/COPS5 were associated with disease-free survival and overall survival. The Jab1/COPS5 level was found to be a possible biomarker for clinical response to chemotherapy in lung cancer patients and for postoperative relapse in breast cancer patients who received adjuvant chemotherapy. In conclusion, this study identified Jab1/COPS5 as novel prognostic markers for lung cancer and breast cancer.

Rhabdomyosarcoma of the breast: Report of a rare malignancy.

Rhabdomyosarcoma (RMS) is an uncommon type of soft-tissue malignancy which mainly influences children. RMS rarely occurs in breast and little of the clinical behavior and treatment strategies were reported. Here, we describe a case of adult female patient with breast RMS. A 34-years-old Chinese woman visited to our hospital complaining palpable mass in her left breast. Seven months ago, the patient was diagnosed as lymphocytic mastitis and received surgical excision in the left breast. Five months later, she noticed a palpable mass again in the left breast. Ultrasonography suspected a malignant lesion and a diagnosis of RMS was made after segmental mastectomy and immunohistochemical staining. Therapy consisted of mastectomy and following neoadjuvant chemotherapy. The patient has remained disease free 30 months post-operatively. We should consider RMS when we see a breast mass. Tissue biopsy and immunohistochemical staining are recommended for diagnosis of RMS in young women. Oncologists should take immediate and active treatment on RMS.

Single-Mode Lasing from "Giant" CdSe/CdS Core-Shell Quantum Dots in Distributed Feedback Structures.

"Giant" semiconductor quantum dots (GQDs) have tremendous potential for applications in laser devices. Here, CdSe/CdS core-shell GQDs (11 monolayers) have been synthesized as lasing gain material. The photoluminescence decay of the GQD ensemble is single-exponential, and the two-photon absorption cross-section is above 105 GM. This article presents a versatile method for fabrication of CdSe/CdS GQD distributed feedback (DFB) lasers by laser interference ablation. A high-quality surface-relief grating structure can be readily created on the GQD thin films, and the relationship between laser beam intensity and surface modulation depth is studied. With appropriate periods, single-mode lasing emission has been detected from these devices under excitation wavelengths of 400 and 800 nm. The laser thresholds are as low as 0.028 and 1.03 mJ cm-2, with the lasing Q-factors of 709 and 586, respectively. Lasing operation is realized from the direct laser interference-ablated QD DFB structures for the first time.

P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients.

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC.

Analysis of differential gene expression profile identifies novel biomarkers for breast cancer.

Breast cancer is the most prevalent cancer diagnosis in women. We aimed to identify biomarkers for breast cancer prognosis. mRNA expression profiling was performed using Gene Chip Human Transcriptome Array 2.0. Microarray analysis and series test of cluster (STC) analysis were used to screen the differential expressed mRNAs and the expression trend of genes. Immumohistochemical staining with 100 clinical specimens was used to validate two differentially expressed genes, ITGA11 and Jab1. In the present study, significantly enriched Gene Ontology (GO) terms and pathways were identified. 26 model profiles were used to summarize the expression pattern of differentially expressed genes. Results of immunohistochemistry were consistent with those of the microarray, in that ITGA11 and Jab1 were differentially expressed with the same trend. Survival analyses using the Kaplan-Meier method demonstrated that breast cancer patients with high levels of either ITGA11 or Jab1 had a significant association with worse prognosis. Our study identified ITGA11 and Jab1 as novel biomarkers for breast cancer.

Clinical and pathologic diagnosis and different diagnosis of syphilis cervical lymphadenitis.

PURPOSE: To study the clinical pathologic characteristics and differential diagnosis of syphilitic cervical lymphadenitis, and to improve the rate of its diagnosis and treatment. METHODS: Retrospectively analyzed the clinical history, Trepone pallidum-ELISA (TP-ELISA), rapid plasma regain test (RPR) and routine pathological examination of the patient diagnosed as syphilis lymphadenitis. And review related literatures. RESULTS: The main clinical presentation was multiple palpable cervical lymph nodes. The multiple nodes were hard, fixed, and the major diameter of the larger one was 2 cm. The main pathological changes included: the capsule was significantly thickened; reactive hyperplasia of lymphoid follicular with sky star phenomenon; occlusive endovasculitis; perivascular inflammation; the proliferation of epithelioid histiocytes can form granulomas with few multinucleated giant cells; few necrosis. TP-ELISA and RPR were positive. CONCLUSIONS: The pathological changes of syphilitic lymphadenitis have a variety of performance with relatively specific and suggestive alterations which requires a combination of clinical history and laboratory test before the diagnosis, and the clinicians can reduce misdiagnosis and missed diagnosis of the disease by increasing vigilance of it.