Intestinal adipocytes transdifferentiate into myofibroblast-like cells and contribute to fibrosis in Crohn's disease.

BACKGROUND AND AIMS: Intestinal fibrotic stenosis is a major reason for surgery in Crohn's disease [CD], but the mechanism is unknown. Thus, we asked whether intestinal adipocytes contribute to intestinal fibrosis. Adipocytes were found to transdifferentiate into myofibroblasts and confirmed to be involved in mesenteric fibrosis in our recent study. Here, we investigated the role and possible mechanisms of intestinal adipocytes in intestinal fibrosis in CD. METHODS: The intestinal tissue of patients with CD with or without fibrotic stenosis [CDS or CDN] and normal intestinal tissue from individuals without CD were obtained to assess alterations in submucosal adipocytes in CDS and whether these cells transdifferentiated into myofibroblasts and participated in the fibrotic process. Human primary adipocytes and adipose organoids were used to evaluate whether adipocytes could be induced to transdifferentiate into myofibroblasts and to investigate the fibrotic behaviour of adipocytes. LPS/TLR4/TGF-ß signalling was also studied to explore the underlying mechanism. RESULTS: Submucosal adipocytes were reduced in number or even absent in CDS tissue, and the extent of the reduction correlated negatively with the degree of submucosal fibrosis. Interestingly, submucosal adipocytes in CDS tissue transdifferentiated into myofibroblast-like cells and expressed collagenous components, possibly due to stimulation by submucosally translocated bacteria. LPS-stimulated human primary adipocytes and adipose organoids also exhibited transdifferentiation and profibrotic behaviour. Mechanistically, TLR4-mediated TGF-ß signalling was associated with the transdifferentiation and profibrotic behaviour of intestinal adipocytes in CDS tissue. CONCLUSIONS: Intestinal adipocytes transdifferentiate into myofibroblasts and participate in the intestinal fibrosis process in CD, possibly through LPS/TLR4/TGF-ß signalling.

Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study.

Purpose: To explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis. Patients and methods: Three independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC). Results: In the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue. Conclusion: A novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Aberrant expression of SPAG6 and NM23 predicts poor prognosis of human osteosarcoma.

Objective: To investigate the expression and clinical significance of sperm-associated antigen 6 and NM23 proteins in human osteosarcoma. Methods: The specimens of conventional osteosarcoma with follow-up from 42 Chinese patients were analyzed in this study, and 12 cases of osteochondroma were considered controls. The expression of SPAG6 and NM23 was inspected using immunohistochemical staining, qRT-PCR, and Western blotting methods. Results: The positive expression rate of SPAG6 protein (71.43%) in 42 cases of osteosarcoma tissue was significantly higher than that (33.33%) in 12 cases of osteochondroma tissues (p < 0.05), while the positive rate of NM23 protein (35.71%) in osteosarcoma tissue was lower than that (58.33%) in osteochondroma tissue (p < 0.05). The mRNA and protein levels of SPAG6 were significantly higher than those of the adjacent normal tissues, while the expression of NM23 was lower in osteosarcoma tissues than that in the controls (p < 0.05 for all). There was a positive relationship between the expression of SPAG6 and pathological grade, metastasis, and Enneking stage (p < 0.05 for all). The overall survival rate of osteosarcoma patients with SPAG6 positive expression was significantly lower than that with SPAG6 negative expression. The relationship between the expression of NM23 and pathological grade, metastasis, and Enneking stage was negative (p < 0.05 for all). The overall survival rate of the osteosarcoma patients with NM23 positive expression was higher than that of the patients with NM23 negative expression (p < 0.05). Conclusion: Overexpression of SPAG6 and low expression of NM23 are negatively related to pathological grade, metastasis, and Enneking stage and prognosis of osteosarcoma patients. This suggested that SPAG6 and NM23 should be considered candidate prognostic biomarkers for patients with osteosarcoma.

Fbxo45 promotes the malignant development of esophageal squamous cell carcinoma by targeting GGNBP2 for ubiquitination and degradation.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly cancers. Fbxo45, a substrate recognition subunit of E3 ligase, is critically involved in tumorigenesis and tumor progression. However, the function of Fbxo45 and the underlying mechanisms have not been elucidated in ESCC. We used cellular and molecular methods to explore the molecular basis of Fbxo45-mediated ESCC development. We found that ectopic overexpression of Fbxo45 promoted the growth of Kyse-150, Kyse30 and ECA-109 cells and inhibited the apoptosis. Moreover, overexpression of Fbxo45 promoted the migration and invasion of ESCC cells. Consistently, knockdown of Fbxo45 exhibited the opposite effects on ESCC cells. Mechanistically, we observed that Fbxo45 binds to GGNBP2 via its SPRY domain and targets GGNBP2 for ubiquitination and degradation. GGNBP2 overexpression exhibited anticancer activity in ESCC cells. Furthermore, Fbxo45 exerted its functions by regulating GGNBP2 stability in ESCC cells. Notably, overexpression of Fbxo45 facilitated tumor growth in mice. Strikingly, Fbxo45 was highly expressed in ESCC tissues, and GGNBP2 had a lower expression in ESCC specimens. High expression of Fbxo45 and low expression of GGNBP2 were associated with poor prognosis in ESCC patients. Fbxo45 was negatively correlated with GGNBP2 expression in ESCC tissues. Therefore, Fbxo45 serves as an oncoprotein to promote ESCC tumorigenesis by targeting the stability of the tumor suppressor GGNBP2 in ESCC.

Case report: Eosinophilic pneumonia associated with vedolizumab therapy in a patient with ulcerative colitis.

Extraintestinal manifestations are common in patients with inflammatory bowel disease, while respiratory involvement is less common. Vedolizumab is a new class of anti-integrin biological agents approved for treating inflammatory bowel disease. In this report, we present the case of a 38-year-old patient with ulcerative colitis for 7 years who developed cough, fever, and pulmonary infiltrates after taking vedolizumab. There was a spontaneous improvement in clinical symptoms and radiological abnormalities after discontinuing vedolizumab and introducing steroids. Despite the rarity of vedolizumab-induced eosinophilic pneumonia, the case reports indicate that patients with unexplained respiratory symptoms that are taking vedolizumab should be fully contemplated.

Clear Cell Carcinoma of the Endometrium: Evaluation of Prognostic Parameters in 27 Cases.

OBJECTIVE: Clear cell carcinoma (CCC) of the endometrium is an uncommon yet aggressive tumor. Few cohort studies are reporting the overall survival time of CCC patients. This study aimed to retrospectively analyze the clinicopathologic features, molecular characteristics and survival data of 27 endometrial CCC patients to improve the understanding of CCC. METHODS: The clinicopathologic features, molecular characteristics and survival data total of 27 CCC patients admitted to the BBMU affiliated hospital (Anhui, China) between January 2005 and December 2018 were retrospectively analyzed. Kaplan-Meier method was used to analyze the prognosis-related factors. RESULTS: The median age of the patients was 60 years (range; 39 to 81 years). The average tumor size was 3.8 cm (range; 0.8 to 13.0cm). Myometrial infiltration greater than 50% was reported in 55.6% of the patients, while the Ki-67 index greater than 50% was reported in 70.4% of the patients. The patients' FIGO (2009) surgical stages were as follows: 18 I, 3 II, 4 III, and 2 IV. Besides, 7 (25.6%) patients had lymphovascular invasion, 3 (11.1%) patients with distant metastasis, including 1 patient with bone metastasis, and 2 with liver metastasis. Adjuvant treatment included 7 with chemotherapy alone, 9 with radiotherapy alone, and 9 with both radiotherapy and chemotherapy. The median overall survival time from the time of CCC diagnosis was 56 months. ER and PR showed negative expression and P16 showed patchy immunostaining. 18 (63%) cases showed Napsin A positive expression. Loss of MSH2, MSH6 and PTEN were seen in 5, 4 and 7 cases respectively. All cases showed HER-2/nue negative expression. CONCLUSION: CCC is a rare and invasive tumor. Age of diagnosis, FIGO stage, tumor size, myometrial infiltration, lymphovascular invasion, distant metastasis, Ki-67 index and P53 expression are important indicators to evaluate patient's prognosis (P = 0.048, P < 0.001, P = 0.016, P = 0.043, P = 0.001, P < 0.001, P = 0.026, and P = 0.007, respectively). CCC has a worse prognosis than endometrioid carcinoma (P = 0.002), and there is no significant difference when compared with uterine papillary serous carcinoma (P = 0.155).

Diverse Roles of F-BoxProtein3 in Regulation of Various Cellular Functions.

Accumulated evidence shows that the F-box protein 3 (FBXO3) has multiple biological functions, including regulation of immune pathologies, neuropathic diseases and antiviral response. In this review article, we focus on the role of FBXO3 in inflammatory disorders and human malignancies. We also describe the substrates of FBXO3, which contribute to inflammatory disorders and cancers. We highlight that the high expression of FBXO3 is frequently observed in rheumatoid arthritis, leukemia, pituitary adenoma, and oral squamous cell carcinoma. Moreover, we discuss the regulation of FBXO3 by both carcinogens and cancer preventive agents. Our review provides a comprehensive understanding of the role of FBXO3 in various biological systems and elucidates how FBXO3 regulates substrate ubiquitination and degradation during various physiological and pathological processes. Therefore, FBXO3 can be a novel target in the treatment of human diseases including carcinomas.

Primary testicular diffuse large B-cell lymphoma: Case series.

RATIONALE: Primary testicular lymphoma (PTL) is a rare type of extranodal non-Hodgkin's lymphoma (NHL). Although data of PTL in patients with diffuse large B-cell lymphoma (DLBCL) are accumulating, there are still patients respond poorly to prognosis. PATIENT CONCERNS: All patients had disease of the DLBCL subtype and those patients had primary involvement of the testis. In our studies, eleven patients had stage I/II disease, and 3 patients had advanced disease with B symptoms. Four patients exhibited a MYC+, BCL2+, and BCL6- expression pattern, 4 patients had a MYC+, BCL6+, and BCL2- expression pattern, and 3 patients had a MYC+, BCL2+, and BCL6+ expression pattern. Additionally, 43% (7/16) of PT-DLBCL patients had a germinal center B-cell-like (GCB) phenotype, while the others had a non-GCB phonotype. DIAGNOSES: In our case, most patients presented with unilateral painless scrotal swelling and the enlargement of the testicles in the first examination. After hospitalization, all patients underwent preoperative imageological examination of the testis and epididymis and postoperative revealed that all patients were the diffuse infiltration of a large number of anomalous lymphocytes. In addition, no invasion of other sites was observed within 3 months after diagnosis. INTERVENTIONS AND OUTCOMES: Underwent orchiectomy on the affected side was performed by urologists after all patients were diagnosed with PTL. Meanwhile, some patients received at least one course of chemotherapy, or received postoperative combined RT and chemotherapy. Because of it particularity, nineteen instances of lymph node region involvement were discovered in 12 patients since the operation. LESSONS: PT-DLBCL has unique biological characteristics, and its treatment modalities are becoming increasingly standardized. In the future, systematic interventions need to be actively considered in the early stages of PTL.

FOXM 1 induces Vasculogenic mimicry in esophageal cancer through ß-catenin /Tcf4 signaling.

OBJECTIVE: To investigate the role of FOXM1, ß-catenin and TCF4 in esophageal cancer (EC) and their relationship to VM (Vasculogenic Mimicry). METHODS: CCK-8 were performed to examine EC cell proliferation in FOXM1 silenced cells. EC cell migration and invasion were investigated through wound healing and Transwell assays, respectively. The formation of pipe like structures were assessed in 3D cultures. The expression of Foxm1, ß-catenin, Tcf4 and E-cadherin were investigated through western blot, RT-qPCR and immunohistochemistry (IHC) staining. The relationship between FOXM1 expression, clinic-pathological features, and overall survival (OS) were further analyzed. RESULTS: A loss of FOXM1 expression correlated with the OS of ESCC patients. FOXM1 silencing led to a loss of cell growth and suppressed cell migration and invasion in ESCC cells. VM structures were identified in ESCC tissues and human EC cell lines. Mechanistically, FOXM1 was found to promote tumorigenesis through the regulation of ß-catenin, Tcf4, and E-cadherin in EC cells, leading to the formation of VM structures. CONCLUSIONS: These findings highlight FoxM1 as a novel therapeutic target in ESCC.

The Emerging Role of Sperm-Associated Antigen 6 Gene in the Microtubule Function of Cells and Cancer.

Accumulated evidence shows that sperm-associated antigen 6 (SPAG6) gene has multiple biological functions. It maintains the normal function of a variety of cells including ciliary/flagellar biogenesis and polarization, neurogenesis, and neuronal migration. Moreover, SPAG6 is found to be critically involved in auditory transduction and the fibroblast life cycle. Furthermore, SPAG6 plays an essential role in immuno-regulation. Notably, SPAG6 has been demonstrated to participate in the occurrence and progression of a variety of human cancers. New evidence shows that SPAG6 gene regulates tumor cell proliferation, apoptosis, invasion, and metastasis. Therefore, in this review, we describe the physiological function and mechanism of SPAG6 in human normal cells and cancer cells. We also highlight that SPAG6 gene may be an effective biomarker for the diagnosis of human cancer. Taken together, targeting SPAG6 could be a novel strategy for the treatment of human diseases including cancer.

Lymphoma of the female genital tract: a clinicopatholngical analysis of 25 cases.

Occurrence of lymphoma of the female genital tract (FGT) is extremely rare, and cohort studies on survival rates of affected patients are sparse. The aim of this study was to retrospectively evaluate the clinicopathological characteristics of patients diagnosed with non-Hodgkin lymphoma of the FGT. This study included 25 women diagnosed with lymphoma of the FGT. Their data on presenting pathological subtype, International Federation of Gynecology and Obstetrics (FIGO) and Ann Arbor staging, International Prognostic Index (IPI) score, treatment, and survival time were collected. Among the 25 patients, the most prevalent histological subtype was diffuse large B-cell lymphoma (23/25). Tumors were most commonly located in the ovary (15/25), with the remainder located in the cervix (7/25) and uterine corpus (3/25). 76% of cases by Ann Arbor were stage III or IV, and 70% of cases by FIGO were stage III or IV. The overall median survival from diagnosis of lymphoma was estimated to be 71 months, with 3-year and 5-year survival rates of 92% and 80%, respectively. The FIGO and Ann Arbor staging and IPI score were significantly correlated with overall survival time.

Aberrant Cyclin E and Hepatocyte Growth Factor Expression, Microvascular Density, and Micro-Lymphatic Vessel Density in Esophageal Squamous Cell Carcinoma.

Cyclin E and hepatocyte growth factor (HGF) have been observed as a multifaceted factor in many cancers, and the assessment of microvascular density (MVD) and micro-lymphatic vessel density (MLVD) has been used to quantify tumor angiogenesis and lymphangiogenesis. The aim of this study was to explore the association between expression of cyclin E, HGF, MVD, and MLVD, and clinicopathologic parameters in esophageal squamous cell carcinoma (ESCC). The expression of cyclin E, HGF, MVD, and MLVD were detected using immunohistochemically anticyclin E, HGF, CD34, and lymphatic vessel endothelial hyaluronan receptor 1 in 168 surgically resected ESCC cases and 30 normal esophageal mucosal samples. The expression levels of cyclin E, HGF, MVD, and MLVD were higher compared to controls. High cyclin E and HGF expression was found more frequently in the tumors larger than 5 cm (P < .001), with poorer differentiation (P = .034) and higher tumor node metastasis (TNM) staging (P = .009) compared to their counterparts. Both MVD and MLVD values were found to be higher in the tumors larger than 5 cm (P < .001), with poorer differentiation (P < .001) and higher TNM staging (P < .001) compared to their counterparts. Furthermore, the expression of MVD and MLVD in both the high cyclin E and high HGF expression groups was significantly higher compared to the low cyclin E and HGF expression groups (P < .001). This study demonstrated that high cyclin E and HGF expression is closely correlated with tumor size, tumor differentiation degree, and TNM stage in patients with ESCC. These findings proposed that cyclin E and HGF could serve as novel molecular markers for preoperational evaluation of ESCC.

Capsaicin induces cytotoxicity in human osteosarcoma MG63 cells through TRPV1-dependent and -independent pathways.

An accumulating body of evidence has shown that capsaicin induces apoptosis in various tumor cells as a mechanism of its anti-tumor activity. However, the effects of capsaicin on osteosarcoma have not been studied extensively. In the current study, we explore the molecular mechanism of capsaicin-mediated tumor suppressive function in osteosarcoma. We found that capsaicin-induced apoptosis and the activation of transient receptor potential receptor vanilloid 1 (TRPV1) in a dose- and time-dependent manner in human osteosarcoma MG63 cells in vitro. Blocking TRPV1 using capsazepine attenuated the capsaicin-induced cytotoxicity, mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity. In addition, the results demonstrated that capsaicin induced the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK), p53 and C-jun N-terminal kinase (JNK). In addition, Compound C (antagonist of AMPK) attenuated the activation of p53, which appeared to be TRPV1 independent. Taken together, the present study suggests that capsaicin effectively causes cell death in human osteosarcoma MG63 cells via the activation of TRPV1-dependent (mitochondrial dysfunction, and overproduction of ROS and JNK) and TRPV1-independent (AMPK-p53) pathways. Thus, capsaicin may be a potential anti-osteosarcoma agent.

Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a micropapillary pattern: cases report and literature review.

Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion renal cell carcinoma (Xp11.2 translocation RCC) was first classified as a distinct type of renal tumor by the World Health Organization in 2004. However, its morphology and clinical manifestations often overlap with those of conventional RCCs. Moreover, a micropapillary pattern (MPP) comprising small papillary cell clusters surrounded by lacunar spaces has never been described in RCC. We compared the clinicopathological and prognostic characteristics of one patient with Xp11.2 translocation RCC exhibiting an MPP (TFE3-M) to those of four patients with conventional Xp11.2 translocation RCC (TFE3-N); all five tumors resembled conventional RCCs on gross pathology. All patients exhibited similar histologies, clinical manifestations, and prognoses, and all underwent radical nephrectomy. However, their characteristics differed significantly from those of other MPP-comprising neoplasms. Both tumor types were positive for TFE3 and vimentin; however, TFE3-M tumor cells expressed epithelial membrane antigen and human melanoma black-45 but not cluster of differentiation 10 (CD10), whereas the TFE3-N cells expressed P504S, CD10, and vimentin but not cytokeratin 7. Our RT-PCR analysis result showed that TFE3-N and TFE3-M tumor cells were identified expressing ASPSCR1-TFE3 and PRCC-TFE3 fusion genes, respectively. These findings suggest that TFE3-M should be classified as a histological subtype of Xp11.2 translocation RCC, although its relationship with other MPP-exhibiting neoplasms remains unclear. The histological characteristics of Xp11.2 translocation RCCs depend on MiT family transcription factors and their gene fusion partners. Xp11.2 translocation RCC should be considered for malignancies presenting with a particular pattern; such malignancies can be identified reliably by their morphological and immunohistochemical profiles.

WISP2 exhibits its potential antitumor activity via targeting ERK and E-cadherin pathways in esophageal cancer cells.

BACKGROUNDS: Emerging evidence has demonstrated that WISP2 is critically involved in cell proliferation, migration, invasion and metastasis in cancers. However, the function of WISP2 in esophageal squamous cell carcinoma (ESCC) is largely unclear. Therefore, we aim to explore the effects and the potential mechanism of WISP2 on proliferation and motility and invasion of ESCC cells. METHODS: Cell proliferation was detected by MTT assay and apoptosis was measured by FACS in ESCC cells after WISP2 downregulation and overexpression. Cell migration and invasion were analyzed by wound healing assay and transwell migration assay, respectively. The expression of ERK-1/2, Slug and E-cadherin was measured by Western blot respectively. IHC was performed to measure the expression of WISP2 in ESCC tissues. RESULTS: WISP2 overexpression is associated with survival in ESCC patients. WISP2 overexpression inhibited cell growth and induced cell apoptosis, suppressed cell migration and invasion in ESCC cells. Moreover, WISP overexpression retarded tumor growth in mouse model. WISP2 downregulation enhanced cell growth, inhibited apoptosis, promoted cell migration and invasion in ESCC cells. Mechanistically, WISP2 exerts its tumor suppressive functions via regulation of ERK1/2, Slug, and E-cadherin in ESCC cells. CONCLUSIONS: Our findings suggest that activation of WISP2 could be a useful therapeutic strategy for the treatment of ESCC.

Fluoxetine reverses brain radiation and temozolomide-induced anxiety and spatial learning and memory defect in mice.

Radiation therapy and concomitant temozolomide chemotherapy are commonly used in treatment of brain tumors, but they may also result in behavioral impairments such as anxiety and cognitive deficit. The present study sought to investigate the effect of fluoxetine on the behavioral impairments caused by radiation and temozolomide treatment. C57BL/6J mice were subjected to a single cranial radiation followed by 6-wk cyclic temozolomide administration and were then treated with chronic administration of fluoxetine. Behavioral tests were carried out to determine the anxiety-like behavior and cognition function of these animals. Long-term potentiation (LTP) in the hippocampus was measured by electrophysiology, and neurogenesis in the dentate gyrus was evaluated by immunohistochemistry. Mice treated with radiation and temozolomide showed increased anxiety-like behavior and cognitive impairment, along with LTP impairment and neurogenesis deficit. Chronic fluoxetine administration could reverse the behavioral dysfunction, enhance LTP, and increase neurogenesis in the hippocampus. NEW & NOTEWORTHY Mice treated with radiation and temozolomide showed increased anxiety-like behavior and cognitive impairment. Chronic fluoxetine administration could reverse the behavioral dysfunction. The effect of fluoxetine might be via rescuing the neurogenesis deficit caused by radiation and temozolomide treatment.

MicroRNA-145 promotes esophageal cancer cells proliferation and metastasis by targeting SMAD5.

OBJECTIVE: To clarify the relative expression and molecular function of microRNA (miR)-145 in esophageal cancer and understand its mechanistic involvement in this disease. MATERIAL AND METHODS: The relative expression of miR-145 in clinical samples was analyzed using the public GSE43732 dataset. The prognostic analysis with respect to miR-145 expression was performed with Kaplan-Meier plot. Cell viability was measured by MTT assay and the anchorage-independent growth was evaluated by soft agar assay. The migration and invasion of esophageal cancer cells were measured using transwell chamber. The regulatory effect of miR-145 on SMAD5 was determined by dual-luciferase reporter assay. The endogenous SMAD5 protein was measured by Western blot. RESULTS: We demonstrated high expression of miR-145 associated with late stage and unfavorable prognosis of esophageal cancer. Ectopic expression of miR-145 mimic significantly stimulated cell proliferation and anchorage-independent growth. Furthermore, high level of miR-145 significantly promoted both migration and invasion in vitro. Notably, we identified SMAD5 as direct target of miR-145, the suppressed expression of which consequently led to increased cell proliferation and migration/invasion. CONCLUSION: Our study uncovered the crucial role of miR-145/SMAD5 in esophageal cancer and highlighted its target potential for diagnostic and therapeutic purpose.

The expressions of CD133, ALDH1, and vasculogenic mimicry in osteosarcoma and their clinical significance.

BACKGROUND AND PURPOSE: Osteosarcoma is an aggressive malignant bone tumor in children and adolescents, which is more likely to recur and metastasize at the early stages. Cancer stem cells (CSC, CD133 is a biomarker of cancer stem cells), angiogenesis, and vasculogenic mimicry (VM) are closely related to tumor metastasis and recurrence. In this study, we investigated the associations among CD133, aldehyde dehydrogenase 1 (ALDH1), and VM in osteosarcoma, and their associations with clinical characteristics. METHODS: Positive rates of CD133, ALDH1, and VM in 96 whole osteosarcoma tissue samples were detected by immunohistochemistry (IHC) and histochemistry staining. Patients' clinical data were also collected. RESULTS: Positive rates of CD133, ALDH1, and VM were significantly higher in osteosarcoma tissues compared with the control tissues. Positive rates of CD133, ALDH1, and VM were positively associated with lymph node metastasis, distant metastasis, Enneking stages, and patients' overall survival (OS). A multivariate analysis indicated that the positive rates of CD133, ALDH1, and VM, as well as the Enneking stages were independent prognostic factors of osteosarcoma. CONCLUSION: The positive rates of CD133, ALDH1, and VM could represent potential biomarkers for metastasis and prognosis, which suggests these molecules might be promising therapeutic targets for osteosarcoma.

Ollier disease: two case reports and a review of the literature.

Ollier disease is a rare tumor with unclear clinicopathological features and pathogenesis. We herein report two cases of Ollier disease in a 15-year-old boy and a 66-year-old man. We analyzed the clinicopathological, radiographical, and histochemical characteristics of Ollier disease in these two cases. Furthermore, we reviewed the literature to better understand the clinicopathological features of this disease. The boy had multiple enchondromas in the metaphysis and upper region of the left femur, and his left leg is short naturally. The 66-year-old man had multiple enchondromas in his left ribs and lower segment of the left femur. He was sent to the hospital because of pathological fracture of the ribs. In addition, he was diagnosed with gastric cancer 4 years before visiting an orthopedic clinic. Ollier disease is a rare bone disease that often renders a typical asymmetrical distribution and is confined to the appendicular skeleton. It is known as a benign bone tumor and has a high risk of malignant transformation into a chondrosarcoma (5%-50%). Correct diagnosis requires radiographic, histochemical, and morphological analyses. Better understanding of the clinical manifestations and pathological features can improve the diagnosis and prevent malignant transformation and deformity, especially in adolescent patient.

Down-regulation of ASIC1 suppressed gastric cancer via inhibiting autophagy.

As autophagy has anti-apoptosis effect and accelerates cell survival, many studies start to target autophagy as a therapeutic strategy for cancer. Acid-sensing ion channels (ASICs) was reported to activate autophagy. However, whether ASICs can regulate gastric cancer through autophagy is unknown. The differentially expressed genes in normal gastric tissue and gastric cancer tissue in patients were investigated by RNA-seq. Expression of ASIC1 and autophagy related 5 (ATG5) was further confirmed by real-time PCR. Effects of knockdown expression of ASIC1 and ATG5 on the growth of gastric SGC-7901 cells were assayed by CCK-8 kit. The animal survival rate and tumor volume in murine heterotopic xenograft model was assayed. The expression of autophagy related genes was enriched in gastric cancer tissue in patients, including ASIC1 and ATG5. Knockdown expression of ASIC1 and ATG5 inhibits the growth of SGC-7901 cells, respectively. ASIC1 regulates ATG5 gene expression in SGC-7901 cells. ASIC1 knockdown extended the survival rate of animals and inhibited the tumor volume in the murine heterotopic xenograft model. This study showed that downregulation of ASIC1 inhibits gastric cancer growth via decreasing autophagy, therefore strongly suggests a therapeutic role for ASIC1 in gastric cancer.