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.

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.

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.

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. Lipopolysaccharide [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.

The adverse prognostic hallmarks in identical twins with Langerhans cell histiocytosis: a clinical report and literature review.

Langerhans cell histiocytosis (LCH) is characterized by uncontrolled proliferation of Langerhans cells accompanying eosinophils. It often attacks children under 10 years of age. LCH in identical twins is very rare and its prognosis is different. Here we report identical-twin sisters with LCH. Computed tomography (CT) revealed osteolytic change in each twin's skull, and the elder exhibited poor eyesight. There were massive histiocyte-like cells surrounded by eosinophils in pathologic specimen of the abnormal lesions, which is typical pathologic finding in LCH. These pathologic cells were positive for S-100 and the cell surface protein CD1 antigen (CD1α), the known markers of LCH. After treating them with surgery, no symptoms were seen in the younger until now. While the older was found another soft mass (about 2.0 cm in diameter) in the left temporal area 18 months later. The same treatment was given to the older after admission, and she is healthy to date. To explore the relationship between hallmarks and the prognosis of identical-twin patients with LCH, we retrieved the 16 literatures (16 identical-twin pairs, 31 patients) listed in PubMed during the past 60 years. The data revealed all those patients who have disseminated to the bone marrow, spleen and liver with symptoms of fever and hepatosplenomegaly exhibited worse prognosis (9 out of the 31 patients). The other identical-twin subjects without infiltration of those organs recovered well. In conclusion, this study reveals the adverse hallmarks of prognosis in identical-twin patients with LCH by reviewing relevant literatures.

Vasculogenic mimicry and aberrant expression of HIF-lα/E-cad are associated with worse prognosis of esophageal squamous cell carcinoma.

This study aims to find good markers for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Vasculogenic mimicry (VM) and the expression of hypoxia inducible factor-lα (HIF-lα)/E-cad protein in ESCC were investigated by immunostaining. The association between VM, HIF-lα/E-cad and clinicopathologic characteristics and 5-year-survival rate of patients with ESCC was analyzed. A total of 160 ESCC specimens were involved in this study and 28 specimens of normal esophageal mucosa served as controls. VM channels were identified in 78 (48.75%) of the 160 ESCC specimens and none of the normal esophageal mucosa was found to have VM. The rates of high-expression of HIF-lα and E-cad in ESCC were 43.75% and 38.75%, while the rates in control were 17.86% and 71.43%, respectively (P<0.05 for all). VM and the expression levels of HIF-lα and E-cad were significantly related to lymph node metastasis, serosa infiltration, PTNM staging and 5-year-survival rates of patients with ESCC (P<0.05 for all). VM was positively correlated with HIF-lα but negatively with E-cad, and HIF-lα was negatively correlated with E-cad (P<0.001 for all). The 5-year-survival rate of patients with ESCC was 6.41% (5/78) in VM group and 65% (52/82) in non-VM group, 7.14% (5/70) in high HIF-lα expression group and 57.78% (52/90) in low HIF-lα expression group. Oppositely, the 5-year-survival rate in high E-cad expression group was 80.65% (50/62) and that in low E-cad expression group was 7.37% (7/98) (P<0.05 for all). Cox multifactor regression analysis indicated that lymph node metastasis, PTNM stage, VM and expression levels of HIF-lα and E-cad were independent risk factors of patients with ESCC (P<0.05 for all). Combined detection of VM, HIF-lα and E-cad plays an important role in predicting the invasion, metastasis and prognosis of patients with ESCC.

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 CD133 in non-small cell lung cancer and its relationship to vasculogenic mimicry.

BACKGROUND: To investigate on expressions and clinical significances of CD133 protein and vasculogenic mimicry (VM) in primary non-small cell lung cancer (NSCLC). METHODS: The specimens of NSCLC from 305 Chinese patients with follow-up were analyzed for CD133 protein expression and VM by immunohistochemical and histochemical staining. RESULTS: In NSCLC, positive rates of 48.9% and 35.7% were obtained for CD133 and VM, respectively. The VM and expression of CD133 were significantly higher in carcinoma than in normal. There were a positive relationship between the VM and expression of CD133 and the tumor grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with CD133 and VM positive expression was lower than that of patients with negative expression. Microvessel density (MVD) was positive corresponded with the grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with MVD≥22's group was shorter than that of patients with MVD<22's group. Pathological-tumor-node-metastasis (pTNM) stage, positive expression of CD133 and VM, postoperative therapy and MVD were independent prognostic factors of NSCLC (P<0.05). Immunohistochemistry revealed an important intratumoral heterogeneity in all four CD133 expression profiles. CONCLUSIONS: VM, MVD and expression of CD133 are related to differentiation, lymph node metastasis, clinical stage, and prognosis. It is suggested that CD133, VM and MVD should be considered as a potential marker for the prognosis.

Overexpression of MMP-1 and VEGF-C is associated with a less favorable prognosis in esophageal squamous cell carcinoma.

BACKGROUND: This study addresses the association of matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-C (VEGF-C) expression in esophageal squamous cell carcinoma (SCC) with clinicopathologic characteristics in the patients. MATERIAL AND METHODS: We profiled the expression of MMP-1 and VEGF-C by cDNA microarray in 4 cases and by reverse transcription-polymerase chain reaction (RT-PCR) in 14 cases of esophageal SCC. Another 90 cases were reviewed by immunohistochemical examination of paraffin-embedded sections. RESULTS: Expression of MMP-1 and VEGF-C mRNA in normal esophageal tissue and tumor tissue was compared. Data were fully consistent with the results of RT-PCR. Immunohistochemistry showed that compared to the normal mucosa MMP-1 and VEGF-C protein expression was upregulated in both esophageal atypical hyperplasia (n = 16) and esophageal SCC. Depth of tumor invasion, lymph node metastasis, and clinical stage were directly associated with prognosis in all cases. Furthermore, median overall survival and disease-free survival were significantly shorter in patients with a higher expression of MMP-1 and VEGF-C than in patients with lower expression levels. CONCLUSION: We demonstrated that the expression of both MMP-1 and VEGF-C mRNA and protein was upregulated in esophageal SCC tissues. Protein expression was associated with progressive tumor stage and poor prognosis in patients with esophageal SCC.

Identification of distinct gene expression profiles between esophageal squamous cell carcinoma and adjacent normal epithelial tissues.

Esophageal squamous cell carcinoma (ESCC) is a predominant type of esophageal cancer, which is a malignant tumor originating from the esophageal mucosa or gland and is aggressive with poor prognosis. Identification of new gene expression patterns would be helpful for providing new targets for the early detection and treatment of ESCC patients. In the present study, we employed cDNA array technology to compare gene expression profiles between ESCC tissues and adjacent normal epithelial tissues from ESCC patients. There was at least a 4-fold change in the expression levels of 72 genes that were significantly increased and 107 genes that were decreased in ESCC compared with normal esophageal epithelium. Among them, genes known to be involved in ESCC were found, including matrix metalloproteinases, transcription factors SOX-4 and SOX-17, the Wingless-type MMTV integration site family member 2, and cell cycle regulators. Moreover, we have newly identified the two genes that are down-regulated in ESCC: monoamine oxidase A, an enzyme that catalyzes monoamines oxidation and 15-hydroxyprostaglandin dehydrogenase [NAD+], a prostaglandin-synthesizing enzyme that physiologically antagonizes COX-2. Likewise, we found the three genes that are up-regulated in ESCC: CD7, a cell surface glycoprotein member of the immunoglobulin superfamily, LIM-domain kinase 1, a small subfamily with an unique combination of two N-terminal LIM motifs and a C-terminal protein kinase domain, and TTK protein kinase, a previously unidentified member of the kinase family. These newly identified genes may be involved in the progression of the tumor and/or represent properties specific to 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.

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.

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.

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).

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.

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.

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.

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.