Does hysteroscopy promote tumor cell proliferation in endometrial cancer?

Peritoneal cytological investigation was carried out inpatients with endometrial cancer, who were subjected to hysteroscopy before the operation (37patients) or were operated on without hysteroscopy. Comparative analysis of the data didnt reveal the role of hysteroscopy in tumor cell dissemination.

Tumor Microenvironment–Responsive Polypeptide Nanogels for Controlled Antitumor Drug Delivery

Tumor microenvironment–responsive polypeptide nanogels belong to a biomaterial with excellent biocompatibility, easily adjustable performance, biodegradability, and non-toxic properties. They are developed for selective delivery of antitumor drugs into target organs to promote tumor cell uptake, which has become an effective measure of tumor treatment. Endogenous (such as reduction, reactive oxygen species, pH, and enzyme) and exogenous (such as light and temperature) responsive nanogels can release drugs in response to tumor tissues or cells to improve drug distribution and reduce drug side effects. This article systematically introduces the research progress in tumor microenvironment–responsive polypeptide nanogels to deliver antitumor drugs and provides a reference for the development of antitumor nanoformulations.

The Key Role of Exosomes on the Pre-metastatic Niche Formation in Tumors

Exosomes or other extracellular vesicles released from cells play an important role in cell-to-cell communication by transferring bio-information (DNA, coding/non-coding RNA, and proteins), which indicates parental cell status to recipient cells in the extracellular environment. Increasingly, evidence shows that tumor-derived exosomes mediate tumor pre-metastatic niche (PMN) remodeling to establish a supportive and receptive niche to promote tumor cell colonization and metastasis. Uptake of genetic information by target cells in the extracellular environment triggers epigenetic changes that contribute to PMN formation. Here, we provide a comprehensive overview of the current understanding of exosomes-mediated reprogramming of cells in PMN formation.

Single-Cell Transcriptomic Analysis Reveals Two Molecularly and Clinically Distinct Subtypes of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, we performed single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues. We found that S100P and SPP1 are two reliable markers for iCCA perihilar large duct type (iCCAphl) and peripheral small duct type (iCCApps). S100P + SPP1- iCCAphl has significantly reduced levels of infiltrating CD3+ T cells, CD56+ NK cells, and increased CCL18+ macrophages compared to S100P-SPP1 + iCCApps. The transcriptor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCApps has significantly more SPP1+ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1- iCCAphl. Moreover, S100P-SPP1 + iCCApps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3 + stemness. Our study extends our understanding of the diversity of tumor cells in iCCA and provides clearer understanding of iCCA classification.

Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression

Brain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor cells (HSPCs) within glioblastoma tissues. Furthermore, we demonstrate a positive link of tumor-associated HSPCs with malignant and immunosuppressive phenotypes. Compared to the medullary hematopoietic compartment, tumor-associated HSPCs contain a higher fraction of immunophenotypically and transcriptomically immature, CD38- cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display signatures of active cell cycle phases. When cultured ex vivo, tumor-associated HSPCs form myeloid colonies, suggesting potential in situ myelopoiesis. In experimental models, HSPCs promote tumor cell proliferation, expression of the immune checkpoint PD-L1 and secretion of tumor promoting cytokines such as IL-6, IL-8 and CCL2, indicating concomitant support of both malignancy and immunosuppression. In patients, the amount of tumor-associated HSPCs in tumor tissues is prognostic for patient survival and correlates with immunosuppressive phenotypes. These findings identify an important element in the complex landscape of glioblastoma that may serve as a target for brain tumor immunotherapies.

A New Sight In The Key Prognosis-Related Proto-Oncogene FYN In Hepatocellular Carcinoma Based On WCGNA Hub-Gene Screening Strategy

Background: Hepatocellular Carcinoma (HCC) is the third deadly cancer worldwide. More breakthroughs are needed in the clinical practice of liver cancer, and new treatment strategies are required to carry out to benefit patients. This study aims to screen out other significant differences in genes associated with LIHC and analyze its prognostic value further. Methods: Here, we use the TCGA-LIHC database and the profiles of GSE25097 from GEO to explore the differential co-expression genes in HCC tissues compared with para-tumor (or healthy) tissues. Then, we utilized WGCNA to screen out differential co-expression genes. Finally, we explored the function of FYN in HCC cells and xenograft tumor models.Results: We identified ten hub genes in the protein-protein interaction (PPI) network, but only three (COLEC10, TGFBR3, and FYN) of them seem to have a close-related to the prognosis. The expression of FYN was negatively correlated with the prognosis of HCC patients. The xenograft model showed that overexpression of FYN could significantly inhibit malignant tumor behaviors and promote tumor cell apoptosis.Conclusion: Thus, FYN may be central to the development of LIHC and maybe a novel biomarker for clinical diagnosis and treatment.

Eosinophilic inflammation promotes CCL6-dependent metastatic tumor growth

Compelling evidence suggests that inflammatory components contribute to cancer development. However, eosinophils, involved in several inflammatory diseases, were not fully explored in cancer metastasis. We show that airway inflammatory eosinophilia and colonic inflammation with eosinophil infiltration are both associated with increased metastasis in mice. Eosinophilia is responsible for increased bone metastasis in eosinophil-enriched Cd3δ-Il-5 transgenic (Il-5 Tg) mice. We also observe increased eosinophils in the malignant pleural effusion of cancer patients with pleural metastasis. Mechanistically, eosinophils promote tumor cell migration and metastasis formation through secreting C-C motif chemokine ligand 6 (CCL6). Genetic knockout of Ccl6 in Il-5 Tg mice remarkably attenuates bone metastasis. Moreover, inhibition of C-C chemokine receptor 1 (CCR1, the receptor of CCL6) in tumor cells reduces tumor cell migration and metastasis. Thus, our study identifies a CCL6-dependent prometastatic activity of eosinophils, which can be inhibited by targeting CCR1 and represent an approach to preventing metastatic disease.

WNT/β-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis

FTO removes the N6-methyladenosine (m6A) modification from genes and plays a critical role in cancer development. However, the mechanisms underlying the regulation of FTO and its subsequent impact on the regulation of the epitranscriptome remain to be further elucidated. Here, we demonstrate that FTO expression is downregulated and inversely correlated with poor survival of lung adenocarcinoma patients. Mechanistically, Wnt signaling induces the binding of EZH2 to β-catenin. This protein complex binds to the LEF/TCF-binding elements at the promoter region of FTO, where EZH2 enhances H3K27me3 and inhibits FTO expression. Downregulated FTO expression substantially enhances the m6A levels in the mRNAs of a large number of genes in critical pathways, particularly metabolic pathway genes, such as MYC. Enhanced m6A levels on MYC mRNA recruit YTHDF1 binding, which promotes MYC mRNA translation and a subsequent increase in glycolysis and proliferation of tumor cells and tumorigenesis. Our findings uncovered a critical mechanism of epitranscriptome regulation by Wnt/β-catenin-mediated FTO downregulation and underscored the role of m6A modifications of MYC mRNA in regulating tumor cell glycolysis and growth.

The Multifaceted Role of Plasminogen in Cancer

Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. They give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. They can also directly promote primary tumor growth and metastasis, and endow tumor cells with mechanisms to evade myelosuppression, thus acquiring drug resistance. In this review, recent studies on the role fibrinolytic factors play in metastasis and controlling cell-death-associated processes are presented, along with studies that describe how cancer cells have exploited plasminogen receptors to escape myelosuppression.

LncRNA PCAT7 promotes the malignant progression of breast cancer by regulating ErbB/PI3K/Akt pathway

Aim: This study aimed to explore the mechanism of lncRNA PCAT7 underlying the progression of breast cancer, which will provide a basis for accurate diagnosis and targeted treatment. Methods: Data from The Cancer Genome Atlas data associated with breast cancer were used to identify the target lncRNA. In vitro experiments were conducted to detect gene expression and the effect of the lncRNA on cancer cell activities. Results: PCAT7 was found to be highly expressed in breast cancer tissue and cells, which activated the ErbB/PI3K/Akt pathway to potentiate cancer cell proliferation, migration and invasion and suppress apoptosis. Conclusion: PCAT7 is likely to promote tumor cell activities by activating ErbB/PI3K/Akt pathway, in turn potentiating tumor malignant progression.