The FGF6 amplification mutation plays an important role in the progression and treatment of malignant meningioma.

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

Mulberry leaf supplementation inhibits skatole deposition by regulating gut microbiota and upregulating liver cytochrome P450 1A1 expression in finishing pigs.

Skatole, a strong fecal odor substance, is generated through microbial degradation of tryptophan in the animal hindgut. It easily accumulates in adipose tissue and affects meat quality. In this study, the effect of mulberry leaf supplementation on skatole in finishing pigs was studied. In a 35-day trial, 20 finishing pigs (barrows and gilts) were fed with a basal diet or basal diet with 6% mulberry leaves. Growth performance of the pigs (n = 10) was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests. Skatole and short-chain fatty acids were detected using HPLC and gas chromatography, respectively. Fecal microbiota were analyzed using 16S rRNA gene sequencing. The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS. The major cytochrome P450 (CYP) enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot. Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line HepG2 in an in vitro test (n = 3). In finishing pigs, mulberry leaf supplementation had no significant effect on the average daily gain, average daily feed intake, and feed conversion ratio (P > 0.05), but reduced skatole levels in feces, serum, and backfat (P < 0.05), and increased acetic acid levels in feces (P = 0.027). Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella (P < 0.05). Indole-3-acetic acid, the intermediate that is essential for skatole production, was significantly reduced in feces by mulberry leaf supplementation (P < 0.05) and was positively correlated with skatole content in feces (P = 0.004). In pigs treated with mulberry leaves, liver CYP1A1 expression was increased (P < 0.05) and was negatively correlated with skatole content in backfat (P = 0.045). The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in hepatic cells. These findings suggest that mulberry leaf supplementation reduces skatole production and deposition in finishing pigs by regulating the gut microbiota and promoting skatole degradation in liver.

Identification and Characterization of a Novel Quanzhou Mulberry Virus from Mulberry (Morus alba).

In this study, we discovered a new virus named Quanzhou mulberry virus (QMV), which was identified from the leaves of an ancient mulberry tree. This tree is over 1300 years old and is located at Fujian Kaiyuan Temple, a renowned cultural heritage site in China. We obtained the complete genome sequence of QMV using RNA sequencing followed by rapid amplification of complementary DNA ends (RACE). The QMV genome is 9256 nucleotides (nt) long and encodes five open reading frames (ORFs). Its virion was made of icosahedral particles. Phylogenetic analysis suggests that it belongs to the unclassified Riboviria. An infectious clone for QMV was generated and agroinfiltrated into Nicotiana benthamiana and mulberry, resulting in no visible disease symptoms. However, systemic movement of the virus was only observed in mulberry seedlings, suggesting that it has a host-specific pattern of movement. Our findings provide a valuable reference for further studies on QMV and related viruses, contributing to the understanding of viral evolution and biodiversity in mulberry.

Synthesis of Cu-Doped TiO2 on Wood Substrate with Highly Efficient Photocatalytic Performance and Outstanding Recyclability for Formaldehyde Degradation.

Photocatalytic oxidation is considered one of the most effective ways to remove formaldehyde from indoor air. However, the use of powder photocatalysts is limited by their low adsorption capacity and strong aggregation tendency. Hence, there is a need for a composite material with good cycling stability and high degradation efficiency. In the present study, a unique wood-based composite is produced by arranging Cu-TiO2 nanoparticles on porous structured wood. The porous structure of wood can adsorb formaldehyde, and the abundant functional groups on the surface can act as a reaction platform for anchoring the Cu-TiO2 nanoparticles. Cu doping facilitates electron interaction between TiO2 and Cu, promotes the transfer of charge carriers, lowers the electron-hole recombination rate, and improves the photocatalytic degradation efficiency of formaldehyde. The photocatalytic efficiency of the wood-based composites was highest (85.59%) when the n(Cu)/n(Ti) ratio was 7%. After nine cycles, the wood composites still had a high degradation rate, indicating good recyclability. Overall, this wood composite is an eco-friendly and promising material for indoor air filtration.

PPy-Coated Mo3S4/CoMo2S4 Nanotube-like Heterostructure for High-Performance Lithium Storage.

Heterostructured materials show great potential to enhance the specific capacity, rate performance and cycling lifespan of lithium-ion batteries owing to their unique interfaces, robust architectures, and synergistic effects. Herein, a polypyrrole (PPy)-coated nanotube-like Mo3S4/CoMo2S4 heterostructure is prepared by the hydrothermal and subsequent in situ polymerization methods. The well-designed nanotube-like structure is beneficial to relieve the serious volume changes and facilitate the infiltration of electrolytes during the charge/discharge process. The Mo3S4/CoMo2S4 heterostructure could effectively enhance the electrical conductivity and Li+ transport kinetics owing to the refined energy band structure and the internal electric field at the heterostructure interface. Moreover, the conductive PPy-coated layer could inhibit the obvious volume expansion like a firm armor and further avoid the pulverization of the active material and aggregation of generated products. Benefiting from the synergistic effects of the well-designed heterostructure and PPy-coated nanotube-like architecture, the prepared Mo3S4/CoMo2S4 heterostructure delivers high reversible capacity (1251.3 mAh g-1 at 300 mA g-1), superior rate performance (340.3 mAh g-1 at 5.0 A g-1) and excellent cycling lifespan (744.1 mAh g-1 after 600 cycles at a current density of 2.0 A g-1). Such a design concept provides a promising strategy towards heterostructure materials to enhance their lithium storage performances and boost their practical applications.

Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer.

Lung cancer is one of the most lethal diseases and therefore poses a significant threat to human health. The Warburg effect, which is the observation that cancer cells predominately produce energy through glycolysis, even under aerobic conditions, is a hallmark of cancer. 6­phosphofructo­2­kinase/fructose­2,6­biphosphatase 2 (PFKFB) is an important regulator of glycolysis. Shikonin is a Traditional Chinese herbal medicine, which has been reported to exert antitumor effects. The present study aimed to investigate the anticancer activity of shikonin in lung cancer. Cell Counting Kit­8 (CCK­8) and colony formation assays were used to analyze proliferation in A549 and H446 cells. Wound healing and Transwell assays were used to measure migration and invasion in A549 and H446 cells. Cell apoptosis was analyzed using flow cytometry. Lactate levels, glucose uptake and cellular ATP levels were measured using their corresponding commercial kits. Western blotting was performed to analyze the protein expression levels of key enzymes involved in aerobic glucose metabolism. Reverse transcription­quantitative PCR was used to analyze the mRNA expression levels of PFKFB2. The results of the present study revealed that PFKFB2 expression levels were significantly upregulated in NSCLC tissues. Shikonin treatment decreased the proliferation, migration, invasion, glucose uptake, lactate levels, ATP levels and PFKFB2 expression levels and increased apoptosis in lung cancer cells in a dose­dependent manner. The overexpression of PFKFB2 increased the proliferation, migration, glucose uptake, lactate levels and ATP levels in lung cancer cells, while the knockdown of PFKFB2 expression exerted the opposite effects. Moreover, there were no significant differences in lung cancer cell migration, apoptosis, glucose uptake, lactate levels and ATP levels between cells with knocked down PFKFB2 expression or treated with shikonin and the knockdown of PFKFB2 in cells treated with shikonin. In conclusion, the results of the present study revealed that shikonin inhibited the Warburg effect and exerted antitumor activity in lung cancer cells, which was associated with the downregulation of PFKFB2 expression.

Case Report: Totally Laparoscopic Resection of Retroperitoneal Paraganglioma Masquerading as a Duodenal Gastrointestinal Stromal Tumor.

Introduction: Retroperitoneal paraganglioma (RPGL) is a rare clinical tumor derived from the retroperitoneal sympathetic paraganglion tissue. Since RPGLs are locate deeply and have no specific symptoms and imaging manifestations at the early stage, which easily causes missed diagnosis or misdiagnosis. In addition, reports on totally laparoscopic resection of RPGLs are scarce due to their close proximity to large vessels, giant size, uncertain location, and unknown malignant status. Case Presentation: We present here the case of totally laparoscopic resection of a 6.4 × 5.4 cm RPGL that was discovered during a workup for discomfort and upper abdominal pain in a 68-year-old female patient, mimicking a gastrointestinal stromal tumor (GIST) of the duodenum, Which was confirmed as a RPGL based on the histopathological and immunohistochemical findings. Conclusions: RPGL is a rare tumor, and the transperitoneal laparoscopic approach for the RPGL is a safe, applicable method with less trauma and quick recovery, which is worth clinical popularizing and application. Moreover, the survival prognosis of RPGL patients are related to metastasis, and lifelong follow-up should be emphasized.

Cytometry Multiplex Bead Antibody Array.

The flow cytometry-based multiplex bead array is an advanced technology using antibody-conjugated multiplex beads to detect soluble targets in a liquid phase. This technology has been widely used for detection of soluble analytes like cytokines, chemokines, allergens, viral antigens, and cancer markers. RayPlex® Multiplex Beads Antibody Array series are developed by RayBiotech Life, Inc. to quantitatively detect a wide range of analytes with high sensitivity to meet increasing need of research and diagnosis.

Pinitol suppresses TNF-α-induced chondrocyte senescence.

Osteoarthritis (OA) is a highly prevalent joint disorder that is tightly correlated with age. As the body ages, cell replication and function decline until homeostasis can no longer be maintained. This process involves cellular senescence as well as replicative senescence. Telomere length, cell cycle arrest, expression of p16 and p53, and the release of senescence-associated ß-galactosidase (SA-ß-Gal) are all markers of cell senescence. In OA joints, chondrocytes undergo cellular senescence prematurely, thereby ceasing to synthesize and maintain cartilage tissue. Upregulation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), and oxidative stress induced by overproduction of reactive oxygen species (ROS) are key events in the pathogenesis of OA. In the present study, we investigated the effects of pinitol, a naturally occurring compound, on the effects of TNF-α on chondrocyte senescence and cell cycle arrest. We found that pinitol has a favorable safety profile in terms of cell viability. Pinitol significantly inhibited cellular senescence and cell cycle arrest in the G0/G1 phase induced by TNF-α. We also found that pinitol could inhibit TNF-α-induced increased telomerase activity and expression of p16 and p53. Importantly, we found that the effects of pinitol may be mediated through rescue of Nrf2 signaling, which is recognized as a key protective factor in OA. This finding was verified through a Nrf2 silencing experiment using Nrf2 siRNA. Together, our findings reveal the potential of pinitol as a safe therapeutic option for the prevention of OA-associated chondrocyte senescence and oxidative stress.

Triptolide inhibits PDGF-induced proliferation of ASMCs through G0/G1 cell cycle arrest and suppression of the AKT/NF-κB/cyclinD1 signaling pathway.

Abnormal proliferation of airway smooth muscle cells (ASMCs) is a hallmark of airway remodeling. Platelet-derived growth factor (PDGF) is known to be a major stimulus inducing the proliferation of ASMCs. It has been reported that triptolide demonstrates protective effects against airway remodeling. In this study, we investigated the antiproliferative effects of triptolide on PDGF-induced ASMCs and its underlying mechanisms. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Quantitative real-time PCR and Western blot analysis were employed to detect the expression of proliferating cell nuclear antigen (PCNA), cyclinD1 and cyclin dependent kinase 4 (CDK4). Proteins involved in the protein kinase B (AKT) and nuclear factor kappa B (NF-κB) signaling pathways were evaluated using Western blot analysis. Triptolide could significantly inhibit cell proliferation, induce cell cycle arrest in the G0/G1 phase, and reduce the expression of PCNA, cyclinD1, and CDK4 in PDGF-treated ASMCs. Levels of phosphorylated AKT, p65 and NF-κB inhibitor α (IκBα) stimulated by the presence of PDGF were markedly suppressed after triptolide treatment. Moreover, triptolide cotreatment with the phosphatidylinositol 3 kinase (PI3k) inhibitor, 2-(4-morpholinyl)-8-phenylchromone (LY294002), could further suppress the proliferation, NF-κB activation and cyclinD1 expression. Similar results were observed after triptolide cotreatment with the NF-κB inhibitor, ammonium pyrrolidinedithiocarbamate (PDTC). Our results suggest that triptolide could inhibit the PDGF-induced proliferation of ASMCs through G0/G1 cell cycle arrest and suppression of the AKT/NF-κB/cyclinD1 signaling pathway.

Quantitative screening of serum protein biomarkers by reverse phase protein arrays.

Screening biomarkers in serum samples for different diseases has always been of great interest because it presents an early, reliable, and, most importantly, noninvasive means of diagnosis and prognosis. Reverse phase protein arrays (RPPAs) are a high-throughput platform that can measure single or limited sets of proteins from thousands of patients' samples in parallel. They have been widely used for detection of signaling molecules involved in diseases, especially cancers, and related regulation pathways in cell lysates. However, this approach has been difficult to adapt to serum samples. Previously, we developed a sensitive method called the enhanced protein array to quantitatively measure serum protein levels from large numbers of patient samples. Here, we further refine the technology on several fronts: 1. simplifying the experimental procedure; 2. optimizing multiple parameters to make the assay more robust, including the support matrix, signal reporting method, background control, and antibody validation; and 3. establishing a method for more accurate quantification. Using this technology, we quantitatively measured the expression levels of 10 proteins: alpha-fetoprotein (AFP), beta 2 microglobulin (B2M), Carcinoma Antigen 15-3(CA15-3), Carcinoembryonic antigen (CEA), golgi protein 73 (GP73), Growth differentiation factor 15 (GDF15), Human Epididymis Protein 4 (HE4), Insulin Like Growth Factor Binding Protein 2 (IGFBP2), osteopontin (OPN) and Beta-type platelet-derived growth factor receptor (PDGFRB) from serum samples of 132 hepatocellular carcinoma (HCC) patients and 78 healthy volunteers. We found that 6 protein expression levels are significantly increased in HCC patients. Statistical and bioinformatical analysis has revealed decent accuracy rates of individual proteins, ranging from 0.617 (B2M) to 0.908 (AFP) as diagnostic biomarkers to distinguish HCC from healthy controls. The combination of these 6 proteins as a specific HCC signature yielded a higher accuracy of 0.923 using linear discriminant analysis (LDA), logistic regression (LR), random forest (RF) and support vector machine (SVM) predictive model analyses. Our work reveals promise for using reverse phase protein arrays for biomarker discovery and validation in serum samples.

Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27(KIP1)-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells.

Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA treatment on cell proliferation, cell cycle distribution, apoptosis, and expression of several cell cycle-related genes in HT-29 cells. The treatment enhanced S-phase cell cycle and apoptosis in HT-29 cells in a dose-dependent manner. Western blot results showed that PCA treatment decreased the expression levels of cyclin A, cyclin D1, and p27(KIP1) but increased those of cyclin-dependent kinase 2 (CDK2) in HT-29 cells. Furthermore, the expression levels of B-cell lymphoma/leukemia-2 (Bcl-2) and B-cell lymphoma/leukemia-xL (Bcl-xL) were down-regulated, whereas the levels of BH3-interacting domain death agonist (Bid), Bcl-2 homologous antagonist/killer (Bak), and cytosolic cytochrome c were significantly upregulated. Thus, the enzymes caspases-9, -3, -8, and -6 were found to be activated in HT-29 cells with PCA treatment. These results indicate that PCA-induced S-phase cell cycle arrest and apoptosis involve p27(KIP1)-mediated activation of the cyclin-A/D1-Cdk2 signaling pathway and the mitochondrial apoptotic pathway.

Mirizzi syndrome with an unusual aberrant hepatic duct fistula: a case report.

Mirizzi syndrome (MS) is a rare complication of chronic cholelithiasis, which is always caused by a calculus in the cystic duct or neck of the gallbladder, resulting in mechanical compression of common bile duct and the gallbladder. It is clinically characterized by abdominal pain, fever, as well as obstructive jaundice. During cholecystectomy, MS is seen as a dangerous adherent and inflammatory tissue in the area of Calot's triangle. In the general population, aberrant right posterior hepatic duct, one of the causes of bile duct injury during duct surgery, is present in 4.8%-8.4% of people. Herein we report a rare case of a 76-year-old female patient, with hepatolithiasis of right posterior lobe and cholecysto-aberrant right posterior hepatic duct fistula. This is a special type of MS; however, interestingly, she did not have any symptoms, and the disease was found by physical examination incidentally. This case highlights another situation, namely, there may be difficulty in diagnosing MS and dissecting for operation. Therefore, to avoid the complication associated with this special situation, the surgeons need to diagnose carefully and adopt an optimal treatment strategy.

Detection of Human Epididymis Protein 4 (HE4) in Human Serum Samples Using a Specific Monoclonal Antibody-Based Sandwich Enzyme-Linked Immunosorbent Assay (ELISA).

BACKGROUND: The human epididymis protein 4 (HE4) may have high specificity in the detection of malignant diseases, making the development of an immunoassay for HE4 essential. METHODS: In our study, a fusion gene was constructed encoded with the HE4 protein. This protein was then produced in the bacterial cells (Escherichia coli) and used to immunize mice in order to eventually generate hybridomas specific to HE4. The hybridoma supernatants were then screened, and four positive anti-HE4 cell lines were selected. These cell lines produce monoclonal antibodies against HE4 epitopes, as demonstrated in the Western blot as well as by direct enzyme-linked immunosorbent assay (ELISA). Using the developed antibodies, we successfully identified several good antibody pairs from the hybridomas, which allowed for the development of a sandwich ELISA to measure HE4 levels. By using the HE4 ELISA, we measured HE4 levels of 60 clinical human serum samples. RESULTS: Compared with the Food and Drug Administration (FDA) approved kit (Roche), our results showed a strong positive correlation to those of the FDA-approved kit. CONCLUSIONS: In summary, highly sensitive antibody pairs were screened against HE4, and a sandwich ELISA was developed as an accurate analytical tool for the detection of HE4 in human serum, which could be especially valuable for diagnosing ovarian carcinomas.

The E3 ligase AtCHIP positively regulates Clp proteolytic subunit homeostasis.

The caseinolytic peptidase (Clp) core proteins are essential for plant growth and development, especially for chloroplast function. Antisense or overexpression of ClpP4, which is one of the Clp core subunits, causes chlorotic phenotypes in Arabidopsis. An E3 ligase gene, AtCHIP, has previously been found to ubiquitylate ClpP4 in vitro. ClpP4 antisense and overexpressing plants that also overexpressed AtCHIP were constructed to explore the effect of AtCHIP on ClpP4. Overexpression of AtCHIP was found to rescue the chlorotic phenotypes of both ClpP4 antisense and overexpressing plants. The unbalanced levels of Clp core proteins in ClpP4 antisense and overexpressing plants with overexpression of AtCHIP were similar to wild-type levels, suggesting that AtCHIP regulates Clp core proteins. The results also show that AtCHIP can interact with ClpP3 and ClpP5 in yeast and ubiquitylate ClpP3 and ClpP5 in vitro. This suggests that AtCHIP is directly related to ClpP3 and ClpP5. Given these results, the inference is that through selective degradation of Clp subunits, AtCHIP could positively regulate homeostasis of Clp proteolytic subunits and maximize the production of functional chloroplasts. Similar results were obtained from transgenic tobacco plants, suggesting that regulation of the Clp protease by AtCHIP is conserved.

Triptolide suppresses airway goblet cell hyperplasia and Muc5ac expression via NF-κB in a murine model of asthma.

BACKGROUND: We have reported that triptolide inhibited pulmonary inflammation in patients with steroid-resistant asthma. In the present study, we investigated whether suppresses airway remodeling and goblet cell hyperplasia, studied the mechanism of triptolide on mucin5ac (Muc5ac) expression in a murine model of asthma. METHODS: BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by repetitive ovalbumin challenge for 6 weeks. Treatments included triptolide (40 µg/kg) and dexamethasone (2mg/kg). The area of bronchial airway (WAt/Pbm), smooth muscle (WAm/Pbm) and mucus index were assessed 24h after the final OVA challenge. Levels of Muc5ac were assessed by ELISA, immunohistology and real-time PCR. Western blot was performed to analyze the phosphorylation of NF-κB p65. RESULTS: Triptolide and dexamethasone significantly reduced allergen-induced increases in the thickness of bronchial airway, smooth muscle and goblet cell hyperplasia. Levels of lung Muc5ac and Muc5ac mRNA were significantly reduced in mice treated with triptolide and dexamethasone. Phosphorylation of NF-κB p65 was significantly reduced in mice treated with triptolide and dexamethasone. CONCLUSION: Triptolide may inhibit airway goblet cell hyperplasia and Muc5ac expression in asthmatic mice via NF-κB. It may be a potential drug for the treatment of patients with severe asthma.

Expression of beclin 1 in non-small cell lung cancer: an immunohistochemical study.

BACKGROUND: Cigarette smoking causes a variety of adverse human health effects, including lung cancer. The molecular events associated with smoke-induced carcinogenesis are thought to be related in part to autophagy. Beclin 1 is an important autophagy-related protein involved in cell death and cell survival. AIM: The purpose of this investigation was to determine the beclin 1 protein and its association with cigarette smoke and the mutation of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). MATERIAL AND METHODOLOGY: Our study included 108 cases of non-small cell lung cancer who were admitted in our hospital. The beclin 1 protein was detected by immunohistochemistry and EGFR mutation by direct sequencing. RESULTS: Beclin 1 expression could be detected in 15 (13.9%) of 108 specimens. These studies investigated that beclin 1 expression was associated with heavy smoking, the gender and the histological type of NSCLC (P = 0.023, 0.035 and 0.039). No association of beclin 1 with EGFR mutation was found (P > 0.05). CONCLUSION: The results from these experiments indicate that heavy smoking may induce the beclin 1 protein in NSCLC.

Tumor-induced perturbations of cytokines and immune cell networks.

Until recently, the intrinsically high level of cross-talk between immune cells, the complexity of immune cell development, and the pleiotropic nature of cytokine signaling have hampered progress in understanding the mechanisms of immunosuppression by which tumor cells circumvent native and adaptive immune responses. One technology that has helped to shed light on this complex signaling network is the cytokine antibody array, which facilitates simultaneous screening of dozens to hundreds of secreted signal proteins in complex biological samples. The combined applications of traditional methods of molecular and cell biology with the high-content, high-throughput screening capabilities of cytokine antibody arrays and other multiplexed immunoassays have revealed a complex mechanism that involves multiple cytokine signals contributed not just by tumor cells but by stromal cells and a wide spectrum of immune cell types. This review will summarize the interactions among cancerous and immune cell types, as well as the key cytokine signals that are required for tumors to survive immunoediting in a dormant state or to grow and spread by escaping it. Additionally, it will present examples of how probing secreted cell-cell signal networks in the tumor microenvironment (TME) with cytokine screens have contributed to our current understanding of these processes and discuss the implications of this understanding to antitumor therapies.