Rare synchronous colorectal carcinoma with three pathological subtypes: A case report and review of the literature.

BACKGROUND: Synchronous colorectal carcinomas (SCRC) are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient. Their incidence is low and the number of pathological types of SCRC is usually no more than two. It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes. Here, we report a rare case of SCRC with three pathological subtypes. CASE SUMMARY: A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month. Colonoscopy displayed an irregularly shaped neoplasm of the rectum, a tumor-like lesion causing intestinal stenosis in the descending colon, and a polypoidal neoplasm in the ileocecum. Subsequently, she underwent total colectomy, abdominoperineal resection for rectal cancer, and ileostomy. After operation, the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon, moderately differentiated adenocarcinoma of the descending colon, and mucinous adenocarcinoma of the rectum. She is now recovering well and continues to be closely monitored during follow-up. CONCLUSION: Preoperative colonoscopy examination, imaging examination, and extensive intraoperative exploration play important roles in reducing the number of missed lesions.

Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p.

Recent research has indicated that Long noncoding RNAs (LncRNAs) are crucial in many disorders, especially tumors. However, the exact role of LncRNA XLOC_006786 (LncRNA-SPIDR-2:1) in malignancies, especially in human osteosarcoma, is unclear. The results of RT‒qPCR, western blotting, CCK-8 assays, and Transwell assays showed that LncRNA XLOC_006786 inhibited osteosarcoma cell proliferation, invasion, and migration, indicating that it may be a tumor suppressor gene in osteosarcoma. We found that LncRNA XLOC_006786 negatively regulated NOTCH3, which is an oncogenic gene in osteosarcoma, as we previously reported. Bioinformatics analysis showed that miR-491-5p may be a direct target of LncRNA XLOC_006786, while NOTCH3 is a key target of miR-491-5p. Then, we verified that LncRNA XLOC_006786 could prevent lung metastatic osteosarcoma in vivo. Taken together, our research showed that LncRNA XLOC_006786 suppresses osteosarcoma proliferation, invasion, and metastasis through the NOTCH3 signaling pathway by targeting miR-491-5p.

Overexpression of chemokine receptor lymphotactin receptor 1 has prognostic value in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an aggressive subtype of renal cell carcinoma. X-C motif chemokine receptor 1 (XCR1) exerts important roles in tumor progression; however, its role in ccRCC is unclear. METHODS: We utilized publicly available data from The Cancer Genome Atlas (TCGA) to assess the role of XCR1 in ccRCC and validated the results in 36 samples from patients with ccRCC who underwent curative resection in Xinqiao Hospital Chongqing. XCR1 overexpression was identified in ccRCC, which was confirmed by qRT-PCR assay and immunohistochemical staining of ccRCC samples. RESULTS: For the TCGA and clinical data, Kaplan-Meier survival analysis revealed that higher XCR1 expression in ccRCC was related to longer overall survival. Cox regression analysis suggested that XCR1 is an independent risk factor for ccRCC. GSEA analysis suggested that XCR1 is associated with the JAK/STAT signaling pathway. XCR1 knockdown by small interfering RNA (siRNA) significantly increased ccRCC cell proliferation and migration, and decreased cell apoptosis. CONCLUSION: We found higher XCR1 expression in ccRCC compared with that in normal tissues is related to longer overall survival in patients with ccRCC. XCR1 knockdown significantly increased RCC cells proliferation and migration, and decreased apoptosis. XCR1 might be used as a prognostic biomarker in ccRCC in the future.

Increased DEF6 expression is correlated with metastasis and poor prognosis in human osteosarcoma.

Metastasis is the primary cause of high mortality in patients with osteosarcoma (OS). However, the molecular mechanisms underlying the regulation of metastatic disease are yet to be determined. Differentially expressed in FDCP 6 homolog (DEF6) has been demonstrated to be correlated with the metastatic behavior of several cancers, such as breast, ovarian and colorectal cancers. However, the role of DEF6 in OS remains unknown. Accordingly, the current study aimed to investigate the relationship between DEF6 expression and the malignant behavior of OS. The results revealed that high levels of DEF6 in OS tissues were associated with advanced clinical stage and metastases. Furthermore, immunohistochemistry results predicted a poor prognosis in 58 human OS specimens. Additionally, DEF6 expression was reported to be upregulated in human OS cell lines compared with a normal osteoblast cell line. small interfering RNA transfection, cell proliferation and colony formation assays, wound healing assays and Transwell assays were performed. DEF6 was not identified to be a major driver of OS cell proliferation, but it significantly contributed to metastatic potential in vitro. In addition, bioinformatics, western blotting and immunohistochemistry results indicated that MMP9 expression was positively correlated with DEF6 expression in human OS. To summarize, the results revealed that increased levels of DEF6 were associated with metastasis and poor prognosis in human OS and that DEF6 expression is positively correlated with MMP9 expression. The results indicated that DEF6 may serve as a potential antimetastatic target for OS.

Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients.

BACKGROUND: Notch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of osteosarcoma and its role and mechanism in osteosarcoma cells have never been reported. MATERIALS AND METHODS: In this study, we performed a clinicopathological analysis of 70 cases of osteosarcoma, with primary focus on survival. Osteosarcoma cell lines MTH and U2OS were used. After knockdown of Notch3 by lentiviral transfection and siRNA, the cell cycle, cell viability, and wound healing capacity were assessed. Subsequently, the Transwell assay was performed, and the expression levels of hairy and enhancer of split-1 (Hes1) and matrix metalloproteinase 7 (MMP7) were detected by RT-PCR and Western blot assay. The expression of MMP7 was also detected after knockdown of Hes1. Animal experiments were performed by injecting the cell lines MTH of Notch3 knockdown into mice tail veins and comparing the development of lung metastasis with the control group. RESULTS: Comparison of survival curves showed that Notch3 expression significantly impacts patient survival. Additionally, multivariate analysis revealed that Notch3 is an independent prognostic factor for osteosarcoma. In in vivo experiments, osteosarcoma-associated pulmonary metastasis in nude mice was reduced after Notch3 silencing. The expression of downstream effector molecule, Hes1, and that of the invasion and metastasis-associated proteolytic enzyme, MMP7, were reduced, and MMP7 was further decreased by Hes1 knockdown in in vitro experiments. CONCLUSION: Notch3 is a prognostic factor for osteosarcoma and might regulate its invasion and metastasis through the downstream target gene Hes1 and effector MMP7.

Intestinal T-cell and NK/T-cell lymphomas: A clinicopathological study of 27 Chinese patients.

BACKGROUND: Intestinal T-cell and NK/T- cell lymphomas are rare and aggressive. The diagnosis is quite difficult, especial in biopsy specimens. This study investigates the clinicopathological features of intestinal T-cell and NK/T-cell lymphomas to aid their differential diagnosis. METHODS: Clinical data of 27 cases were collected. Including extranodal NK/T-cell lymphoma, nasal type (ENKTCL-N), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), anaplastic large-cell lymphoma, ALK+ (ALCL, ALK+) and angioimmunoblastic T-cell lymphoma (AITL). The histologic features, immunohistochemical findings, T-cell receptor gene rearrangement results, and follow-up data were analyzed, with review of literature. RESULTS: The age of the patients (N = 27) was 15-85 years (mean, 47.5 years), and male:female ratio, 3.5:1. Abdominal pain and B symptoms were the most common symptoms. Although 85.2% of the patients were in clinical stage I-II, 59.3% died within 1 year. MEITL showed certain distinctive clinic opathological features from ENKTCL-N. Compared to lesions at other sites, there were no differences in the morphological features, immunophenotype and TCR gene rearrangement of intestinal ENKTCL-N, PTCL, NOS, ALCL, ALK+ and AITL. CONCLUSION: Intestinal T-cell and NK/T-cell lymphomas are a heterogeneous group of lymphomas. They could be classified to 5 histological subtypes in our study. ENKTCL-N and MEITL formed the majority of the tumor types. Each subtype has distinctive pathological features, but most of them have diamal prognosis.

A novel device in parathyroid autotransplantation for 6 patients with secondary hyperparathyroidism - Case series.

BACKGROUND: Secondary hyperparathyroidism(sHPT) is one of the most serious complications in long-term hemodialysis patients. Patients may suffer from metabolic bone diseases, severe atherosclerosis and undesirable cardiovascular events. Endoscopic parathyroidectomy with autotransplantation is a treatment option for those who do not respond to clinical management. METHODS: 6 patients with secondary hyperparathyroidism were treated with endoscopic parathyroidectomy and autotransplantation. Pieces of parathyroid tissue were squeezed in our novel self-made device and injected into brachioradialis. RESULTS: Preoperative symptoms were alleviated, and the serum PTH and alkaline phosphatase levels, hyperphosphatemia, and hypercalcemia were improved or normalized in all 6 patients. The preparation time of parathyroid fragments for autotransplantation was less than 10 min in all 6 patients.Pathological examinations revealed parathyroid cells remains active. CONCLUSION: Application of the novel squeezing device is an economic, effective and safe way in endoscopic parathyroidectomy and autotransplantation for patients with secondary hyperparathyroidism.

TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis.

BACKGROUND: Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear. METHODS: We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing. RESULTS: We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models. CONCLUSIONS: Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

Blood-Brain Barrier Disruption, Sodium Fluorescein, And Fluorescence-Guided Surgery Of Gliomas.

PURPOSE: Sodium fluorescein (SF) is an ideal dye for intraoperative guided-resection of high-grade gliomas (HGGs). However, it is not well understood whether the SF-guided technique is suitable for different grades of gliomas, and the correlation between fluorescence and pathology is also not yet clear. MATERIALS AND METHODS: In this study, we investigated 28 patients, including 23 patients with HGG and 5 patients with low-grade glioma (LGG). All patients were treated using the SF-guided technique on a Pentero 900 microscope (Carl Zeiss, Oberkochen, Germany). Claudin-5 immunohistochemical (IHC) staining for the tumours and peritumour tissues was analyzed. RESULTS: Intraoperative yellow fluorescence was noted in all the HGGs but not in the LGGs. Claudin-5 expression in the blood brain barrier endothelial cells was downregulated and disconnected in the HGGs (p < 0.05), but had no difference or slightly decreased in the LGGs (p > 0.05). CONCLUSIONS: The SF-guided technique is suitable for HGG surgery but not for LGG surgery. Downregulation of claudin-5 expression may contribute to the presence of yellow fluorescence in the glioma in SF-guided surgery.

TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway.

Osteosarcoma is the most common type of bone cancer, and the second leading cause of cancer-related death in children and young adults. Osteosarcoma stem cells are essential for osteosarcoma initiation, metastasis, chemoresistance and recurrence. In the present study, we report that: 1) higher TSSC3 expression indicates a better prognosis for osteosarcoma patients, and; 2) overexpression of TSSC3 significantly decreases sphere-forming capacity, tumor initiation, stemness-related surface markers and Nanog expression in osteosarcoma cells. We also discovered that higher Nanog expression correlates to a worse prognosis for osteosarcoma patients, and overexpression of Nanog increases the stem-related phenotype in osteosarcoma cells. Knockdown of Nanog suppresses these phenotypes. Inhibition of Nanog expression and self-renewal of osteosarcoma cells by TSSC3 overexpression appears to be mediated through inactivation of the Src/Akt pathway. In the clinical setting, expression of TSSC3, p-Src and Nanog is associated with recurrence, metastasis and surgical intervention. Lower TSSC3 expression, higher Nanog expression or higher p-Src expression indicate a poor prognosis for osteosarcoma patients. Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.

[Expressions of CXCL13, CD10 and bcl-6 in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified].

OBJECTIVE: To study the value of immunomarkers CXCL13, CD10, bcl-6 in pathologic diagnosis of angioimmunoblastic T-cell lymphoma (AITL). METHODS: One hundred and fifteen cases of AITL, 30 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 30 cases of reactive lymph nodes with paracortical hyperplasia (RH) encountered during the period from January, 1990 to January, 2008 were retrieved from the archival files of the Department of Pathology, West China Hospital of Sichuan University, China. The morphologic features were reviewed and compared. Immunohistochemical study was performed by SP method for CXCL13, CD10, bcl-6, CD21, CD3epsilon, CD3, CD45RO, CD20 and Ki-67. TCR-gamma gene rearrangement study was also carried out. RESULTS: Regressed follicles were evident in 7.8% (9/115) of AITL cases, 6.7% (2/30) of PTCL, NOS cases and 83.3% (25/30) of RH cases, respectively. A marked increase of number of arborizing venules was shown in 98.3% (113/115) of AITL cases, 63.3% (19/30) of PTCL, NOS cases and 76.7% (23/30) of RH cases, respectively. In lymph nodes with paracortical hyperplasia, the expression of CXCL13, CD10 and bcl-6 were restricted to the germinal centers. In AITL, 96.5% (111/115) of cases showed CXCL13 expression, in contrast to 26.7% (8/30) of PTCL, NOS. Expression of CD10 and bcl-6 were found in the neoplastic cells in 50.4% (58/115) and 78.3% (90/115) of AITL, and 3.3% (1/30) and 3.3% (1/30) of PTCL, NOS, respectively. Irregular meshworks of CD21-positive follicular dendritic cells were found in all the AITL cases. Clonal TCR-gamma rearrangement was detected in 83% (83/100) of the AITL cases. CONCLUSIONS: AITL is a type of lymphoma originated from the follicular helper T cells. Detailed morphologic assessment and use of immunohistochemical markers are essential for accurate diagnosis.

[Splenic lymphangioma: clinicopathologic and immunohistochemical study of 18 cases and review of literature].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of splenic lymphangioma. METHODS: Eighteen cases of splenic lymphangioma were retrieved from the pathology archives during the period between January 1990 to December 2005. The clinicopathologic features were analyzed. Immunohistochemical study was performed on the paraffin sections of 16 cases. RESULTS: The age of the patients ranged from 9 to 72 years (median = 40 years). Thirteen patients were males and 5 were females. Clinically, the tumor could be asymptomatic or present with abdominal symptoms and hypersplenism. Follow-up information was available in 13 patients (72.2%) and the duration varied from 5 months to 15 years. All 13 patients had an uneventful clinical course, with no evidence of residual disease, local recurrence or metastasis. Gross examination showed splenic enlargement. The tumor appeared as cystic (8/18), solid (5/18) or honeycomb mass (5/18), either solitary (5/18) or multifocal (13/18). Histologically, splenic lymphangioma could be subclassified as cavernous (9/18), cystic (5/18) or mixed (4/18). Immunohistochemical study showed that the positivity rates for CD9 and D2-40 were 100% and 43.8% respectively. CONCLUSIONS: Splenic lymphangioma is a rarely encountered entity that can be misdiagnosed as a splenic hemangioma. A definite diagnosis depends on pathologic examination.