The STAT3 pathway promotes epithelial-mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of the key epithelial-mesenchymal transition transcription factor SNAIL in a DNA binding-independent manner. However, the mechanism by which STAT3 is recruited to the SNAIL promoter to upregulate its expression is still elusive. In our study, the lysine methylation binding protein L3MBTL3 is positively associated with metastasis and poor prognosis in female patients with breast cancer. L3MBTL3 also promotes epithelial-mesenchymal transition and metastasis in breast cancer. Mechanistic analysis reveals that L3MBTL3 interacts with STAT3 and recruits STAT3 to the SNAIL promoter to increase SNAIL transcription levels. The interaction between L3MBTL3 and STAT3 is required for SNAIL transcription upregulation and metastasis in breast cancer, while the methylated lysine binding activity of L3MBTL3 is not required for these functions. In conclusion, L3MBTL3 and STAT3 synergistically upregulate SNAIL expression to promote breast cancer metastasis.

Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis, and dreadful mortality. Chemotherapy is a commonly used approach for OS treatment but is limited by the development of drug resistance and long-term adverse effects. To date, OS still lacks the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS2@CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS2@CP NPs showed superior Fenton reaction catalytic activity. FeS2@CP NPs-based CDT efficaciously eradicated the tumor cells by initiating dual-effect of killing of apoptosis and ferroptosis. Furthermore, the generated heat from FeS2@CP under near-infrared region II (NIR-II) laser irradiation could not only inhibit tumor's growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy showed excellent osteosarcoma treatment effects both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.

Appendiceal endometriosis with intestinal metaplasia is particularly challenging to diagnose preoperatively based on clinical features. Microscopically, it can mimic malignant transformation into mucinous neoplasms of the appendix. The present study reports a case of a 47-year-old woman who presented with abdominal pain that was not related to her menstruation. The preoperative diagnosis and laparoscopic evaluation were chronic appendicitis. No mucinous or haemorrhagic secretions were present within the abdominal cavity. Pathological evaluation revealed conventional endometriosis with intestinal-type metaplasia of the epithelium. An inverse pattern of cytokeratin (CK)7, paired-box 8, estrogen receptor, CK20, caudal type homeobox transcription factor 2 and mucin 2 immunoreactivity between intestinal-type and endometrial-type endothelium was observed. Infiltration and replacement of the appendiceal wall by marked levels of acellular mucin, a lack of stromal components and a DNA mismatch repair protein profile were vital in diagnosing appendiceal endometriosis without appendiceal mucinous neoplasms (AMNs). The lesion of appendiceal endometriosis are usually superficial and small in previously reported cases but was deeply invasive in our case. A careful histopathological examination is necessary for diagnosing and distinguishing the histologic imitators of AMN.

Abstract Active STAT3 pathway promotes epithelial mesenchymal transition, migration, invasion and metastasis in cancer. STAT3 upregulates the transcription of epithelial mesenchymal transition key transcription factor SNAIL through DNA-binding independent way. However, the mechanism that how is STAT3 recruited to SNAIL promoter to upregulate transcription in DNA independent way is still unclear. In our study, we found a lysine methylated binding protein L3MBTL3 was positively associated with metastatic and poor prognosis in breast cancer. L3MBTL3 also promoted epithelial-mesenchymal transition, migration, invasion and metastasis in breast cancer. Mechanism analysis found L3MBTL3 interacted with active STAT3 and recruited active STAT3 on SNAIL promoter to up-regulated SNAIL transcription. The interaction between L3MBTL3 and active STAT3 was required for SNAIL transcription up-regulation, migration and invasion in breast cancer, while the methylated lysine binding activity of L3MBTL3 is not required for these functions. In conclusion, L3MBTL3 and active STAT3 collaboratively up-regulate SNAIL transcription to promote breast cancer metastasis.

Background:In recent years, with the development of transcriptome sequencing, the molecular characteristics of tumors are gradually revealed. Because of the complexity of tumor transcriptome, there is a need to look for the molecular signatures which can be used to evaluate the tissue origin and cell stemness of tumors in order to promote the diagnosis and treatment of tumors.Methods:Tumor tissue-specific gene sets (TTSGs) consisting of 200 genes were selected using RNA expression data of 9,875 patients from 33 tumor types. t-distributed Stochastic Neighbor Embedding (t-SNE) was used for dimensionality reduction and visualization of TTSGs in each tumor type. To evaluate oncogenic dedifferentiation and loss of cell stemness, Euclidean distance from each sample to a human embryo single-cell RNA-seq dataset (GSE36552) of TTSGs was calculated as TTSGs index indicating dissimilarity of tumors and embryo. TTSGs index was evaluated for prognosis in each tumor type. Two published signature indexes, the mRNA signature index (mRNAsi) and CIBERSORT, were compared to assess the correlation between the TTSGs index with cell stemness and immune microenvironment. Finally, the difference of prognosis, immune microenvironment and radiotherapy outcomes were compared between patients with high and low TTSGs index.Results:In this study, all 33 tumor types in The Cancer Genome Atlas (TCGA) were embedded into isolated clusters by t-SNE and confirmed by k-nearest neighbors (kNN) algorithm. Clusters of squamous-cell carcinoma were adjacent to each other revealing similar histologic origin. Basal-like breast cancer was separated from luminal and HER-2-amplified subtypes and closed to squamous-cell carcinoma. TTSGs index was related to overall survival outcomes in cancers derived from liver, thyroid, brain, cervical and kidney. There was a positive correlation between mRNAsi and TTSGs index in pan-kidney and pan-neuronal cancers. Furthermore, cell fractions of M2 macrophages and total leukocytes increased in the group with higher TTSGs index. Patients with higher TTSGs index had longer overall survival time and less radiation therapy resistance compared to patients with lower TTSGs index.Conclusions:The signature of TTSGs is related to tumor expression features that distinguish tumors of different histologic origin using t-SNE. The signature also relates to prognosis of certain kinds of tumors.

The purpose of this study was to investigate the diagnostic performance of a novel semi-quantitative dual-energy computed tomography (DECT) scoring system in monitoring urate deposition. This study included 287 patients with gout. All patients underwent ankle/foot DECT scans. DECT scores at different stages were compared and their diagnostic efficacies evaluated. Associations between DECT scores and clinical variables were evaluated. Gouts with positive DECT results in early, middle, and late stages were 78.5 %, 81.4 %, and 95.8 %, respectively (all P > .05). The total and ankle/midfoot DECT scores at different stages significantly increased with disease duration (all P < .05). DECT scores of 4 regions excluding the first metatarsophalangeal joint in early and middle stages were lower than those in late stage (all P < .05). DECT scores achieved excellent diagnostic performance for differentiating gout in early stage from middle and late stages (area under the curve, 0.923 and 0.949), with high sensitivity, specificity, positive predictive value, and negative predictive value (all > 85 %). Total DECT score was highly positively correlated with the volume of urate crystals (R = 0.873, P < .001). Disease duration, serum uric acid level, bone erosion, and Achilles tendon involvement significantly affected total DECT scores (all P < .01). In conclusion, longer disease duration, higher serum uric acid levels, bone erosion, and Achilles tendon involvement were closely associated with total DECT scores. DECT scoring system may be an invaluable tool for gout diagnosis owing to its high detection efficacy and a surrogate method to evaluate the amount of urate crystals and erosion of surrounding tissues.

Mammals have several organs comprising various cells with different functions. Furthermore, eukaryotic cells are compartmentalized into functionally distinct organelles. Thus, for good organismal health, exosomes, which play an important role in cell-to-cell communication, interact closely with oxidative stress. Oxidative stress, which is recognized as a type of intracellular second signal, is aggravated by reactive species. As a subtype of reactive species, reactive oxygen species (ROS) can be produced on the extracellular face of the plasma membrane by NADPH oxidases, via the mitochondrial electron transport chain, in peroxisomes, and in the lumen of the endoplasmic reticulum. The scavenging of ROS is mainly dependent on peroxiredoxins, including GSH peroxidases, peroxiredoxins 3 and 5, and thioredoxin reductase. Intracellular ROS increase the number of intracellular multivesicular bodies (MVBs) by restraining their degradation in lysosomes, thereby enhancing the release of exosomes under the synergy of the depletion of exofacial GSH, which can be regulated by oxidative stress. In contrast, higher ROS levels can decrease the yield of exosomes by activating cellular autophagy to degrade MVBs. Moreover, exosomes can transfer the characteristics of parent cells to recipient cells. Here, we review the interaction between oxidative stress and exosomes in the hope of providing insights into their interplay.

Clear cell renal cell carcinoma (ccRCC) is a primary pathological subtype of RCC and has poor clinical outcome. Krüppel-like factors (KLFs), which are zinc-finger proteins, may be involved in ccRCC development and progression. KLFs belong to the zinc-finger family of DNA-binding transcription factors and regulate transcription of downstream target genes. KLFs are involved in cancer development. The present study aimed to investigate the role of KLFs in ccRCC prognosis. The Cancer Genome Atlas database and multifactorial analysis showed that KLFs were widely expressed in pan-cancers and KLF2 was an independent protective factor for ccRCC prognosis. Patients with low KLF2 expression had a low survival probability and expression of KLF2 was downregulated in patients with ccRCC with high pathological grade (II + III vs. I). In addition, western blot and reverse transcription-quantitative PCR revealed that KLF2 was expressed at low levels in ccRCC cell lines and overexpression of KLF2 inhibited cell migration. In addition, KLF2 expression was negatively correlated with methylation. KLF2 expression was elevated following treatment of ccRCC cells with DNA methyltransferase inhibitor. A prognostic risk index prediction model was constructed based on multiple Cox regression. The receiver operating characteristic curve was 0.780 (area under curve >0.5). Furthermore, Gene Ontology enrichment analysis showed that 'cell adhesion' and 'junction' were negatively correlated with KLF2 and that high-risk group exhibited significantly activated 'epithelial-mesenchymal transition'. Western blot analysis showed that overexpression of KLF2 increased expression of E-cadherin, while decreasing levels of N-cadherin and vimentin. The present study highlighted the role of KLFs in ccRCC prognosis prediction and provides a research base for the search of validated prognostic biological markers for ccRCC.

Metastasis is the hallmark of failed tumor treatment and is typically associated with death due to cancer. Transient receptor potential (TRP) channels affect changes in intracellular calcium concentrations and participate at every stage of metastasis. Further, they increase the migratory ability of tumor cells, promote angiogenesis, regulate immune function, and promote the growth of tumor cells through changes in gene expression and function. In this review, we explore the potential mechanisms of action of TRP channels, summarize their role in tumor metastasis, compile inhibitors of TRP channels relevant in tumors, and discuss current challenges in research on TRP channels involved in tumor metastasis.

Tumor-derived exosomes (TDEs) are actively produced and released by tumor cells and carry messages from tumor cells to healthy cells or abnormal cells, and they participate in tumor metastasis. In this review, we explore the underlying mechanism of action of TDEs in tumor metastasis. TDEs transport tumor-derived proteins and non-coding RNA to tumor cells and promote migration. Transport to normal cells, such as vascular endothelial cells and immune cells, promotes angiogenesis, inhibits immune cell activation, and improves chances of tumor implantation. Thus, TDEs contribute to tumor metastasis. We summarize the function of TDEs and their components in tumor metastasis and illuminate shortcomings for advancing research on TDEs in tumor metastasis.

Background Kimura’s disease is a rare, benign, chronic inflammatory disease that presents as painless, solid masses mainly affecting the deep subcutaneous areas of the head and neck, especially the salivary glands, parotid glands and nearby lymph nodes. It is characterized by elevated peripheral blood eosinophil and Immunoglobulin E (IgE) levels. Case presentation A 31-year-old Asian male presented with an orbital space-occupying lesion lasting for 1.5 years. Ten years prior, surgical excision of bilateral fossa cubitalis and groin masses was performed, and the pathological examination showed "lymphoproliferative disease". One year later, masses reappeared near the surgical sites; they grew slowly and shrank after glucocorticoid treatment . At this point, admission examinations showed in the peripheral blood an eosinophil proportion of 13.4%, a total IgE level of 26,900.00 IU/mL, prurigo present on the whole body, and multiple palpable masses near the bilateral fossa cubitalis and groin. The left eyeball was exophthalmic. The left elbow mass was excised, and the pathological examination confirmed Kimura’s disease. Oral glucocorticoid therapy is taken and tapering regularly. The eosinophil count returned to normal, the IgE level gradually decreased, the orbital space-occupying lesion and elbow and groin masses shrank significantly, and the whole-body skin prurigo disappeared. Currently, the patient has been in a stable condition for eighteen months. Conclusion Our case provides a novel insight that Kimura’s disease should be involved in the differential diagnosis of inflammatory lesion mass of orbit and also supports systemic regular glucocorticoid as a valuable therapy of such condition, but close follow-up and long-term observation are crucial.