The value of serum RASSF10 hypermethylation as a diagnostic and prognostic tool for gastric cancer

Abstract

The tumor-suppressing role of Ras-association domain family 10 (RASSF10) has been described in several types of cancers. Here, we evaluated the potential use of the hypermethylation status of the RASSF10 promoter in serum as a new diagnostic and prognostic tool in gastric cancer (GC). We used bisulfite sequencing polymerase chain reaction to examine RASSF10 methylation levels in serum and/or tumor samples from 82 GC, 45 chronic atrophic gastritis (CAG), and 50 healthy control patients. In the serum of GC patients, the median level of RASSF10 methylation was higher at 47.84 % than those in the serum of CAG and healthy control patients at 11.89 and 11.35 %, respectively. The median level of RASSF10 methylation in GC tumor tissue was similarly high at 62.70 %. Furthermore, RASSF10 methylation levels were highly correlated between paired serum and tumor samples from GC patients. We performed receiver-operating characteristic curve analyses to verify that serum RASSF10 methylation levels could effectively distinguish GC from control patients. Moreover, multivariate analyses showed that high serum RASSF10 methylation levels in GC patients were associated with large tumors, lymph node metastasis, and high carcinoembryonic antigen (CEA) levels. Survival analyses showed that GC patients with high serum RASSF10 methylation levels had shorter overall and disease-free survival after D2 lymphadenectomy than those with low levels. High serum RASSF10 methylation levels were also an independent predictor of tumor recurrence and GC patient survival. In conclusion, serum RASSF10 promoter methylation levels can serve as a valuable indicator for the diagnosis and prognosis of GC in the clinic.

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Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

Abstract

Purpose

We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications.

Methods

Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C).

Results

According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n = 6); Before-S or N and After-C, Group II (n = 9); and Before-S or N and After-S or N, Group III (n = 8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups.

Conclusions

CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

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Anatomy of the AGN in NGC 5548: V. A clear view of the X-ray narrow emission lines

Whewell, M; Branduardi-Raymont, G; Kaastra, JS; Mehdipour, M; Steenbrugge, KC; Bianchi, S; Behar, E; Whewell, M; Branduardi-Raymont, G; Kaastra, JS; Mehdipour, M; Steenbrugge, KC; Bianchi, S; Behar, E; Ebrero, J; Cappi, M; Costantini, E; Marco, BD; Gesu, LD; Kriss, GA; Paltani, S; Peterson, BM; Petrucci, P-O; Pinto, C; Ponti, G; - view fewer (2015) Anatomy of the AGN in NGC 5548: V. A clear view of the X-ray narrow emission lines. Astronomy & Astrophysics , 581 , Article A79. 10.1051/0004-6361/201526742 . Green open access

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Fragile X Mental Retardation Protein controls Ion Channel Expression and Activity

Ferron, L; (2016) Fragile X Mental Retardation Protein controls Ion Channel Expression and Activity. Journal of Physiology 10.1113/JP270675 . (In press).

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Thermal re-radiation modelling for the precise prediction and determination of spacecraft orbits.

Adhya, S.; (2005) Thermal re-radiation modelling for the precise prediction and determination of spacecraft orbits. Doctoral thesis, University of London. Green open access

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Anatomical basis of the coordination between smooth and striated urethral and anal sphincters: loops of regulation between inferior hypogastric plexus and pudendal nerve. Immuno-histological study with 3D reconstruction

Abstract

Purpose

(1) Describe both nervous pathways to the sphincters, and highlight the anatomical support of their coordination. (2) Obtain a 3D representation of this complex innervation system.

Methods

A computer-assisted anatomical dissection technique was used. Serial histological sections were cut in the pelvis of four female human foetuses (aged 19–32 weeks of gestation). The sections were treated with conventional staining, and with seven different immunostainings. The sections were digitalized and, finally, a 3D representation was built from the corresponding images.

Results

Myelinated and sensory fibres were detected at the inferior hypogastric plexus (IHP) level. Our analysis showed that most of the afferent sensory fibres come from the urinary and anal sphincters through the anterior and posterior branches of the IHP respectively. A highly positive nitrergic (anti-NOS1) and sensitive (anti-CGRP) labelling was found in the external layer of the urethral sphincter. The 3D representation allowed describing the two components of the innervation system. A sensory-motor regulation loop was found for both sphincters.

Conclusion

A 3D description of the components of both nervous pathways to the sphincters has been established. Our findings on the innervation of the sphincters tend to question the classical infra/supra levatorian muscle description. The coordinated work of the internal and external layers of the anal and urethral sphincter is probably mediated by multiple roles regulation.

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A resected case of neuroendocrine carcinoma of the stomach with unusual lymph node metastasis

Abstract

Gastric endocrine cell carcinoma is a relatively rare tumor. We experienced a case of early gastric cancer in which an endocrine cell carcinoma was identified within a differentiated adenocarcinoma, and a component of this endocrine cell carcinoma had metastasized to lymph nodes of the stomach. In its 2010 revision regarding digestive system tumors, WHO classified cancer cells with characteristics of both glandular system cells and neuroendocrine cells as mixed adeno neuroendocrine carcinoma (MANEC) under the neuroendocrine carcinoma (NEC) category. In this case, we observed an endocrine cell carcinoma continuous with an intramucosal differentiated adenocarcinoma, and cancer cells with an irregular gland duct structure were observed in the proliferative portion of the submucosal tissue. In addition, there was a 35 mm size lymph node metastasis in the lesser curvature of the stomach consisting entirely of poorly differentiated cancer cells with polymorphic, highly atypical nuclei and scant cytoplasm. Immunohistological analysis showed that the endocrine carcinoma in the gastric mucosa was chromogranin A positive and the infiltrated area of the submucosal tissue was also chromogranin A positive. The lymph node metastasis was positive not only for chromogranin A, but also for Synaptophysin and CD56. Furthermore, the Ki67 labeling index was high at approximately 80 % for the gastric endocrine cell carcinoma and approximately 90 % for the lymph node metastases. Until now, there are no reports related to the patients with early gastric cancer accompanied with lymph node metastasis of MANEC. This case is very interested in considering the mechanism of lymph node metastasis of MANEC. The patient has shown no sign of recurrence for 1 year and 4 months after postoperative chemotherapy.

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