Initial screening of gastric cancer using oral contrast-enhanced trans-abdominal ultrasonography in rural asymptomatic individuals.

BACKGROUND & AIMS: Initial screening for high-risk population of gastric cancer (GC) is needed in rural areas of large-population countries. This study aims to explore the feasibility of applying noninvasive ultrasonography as an initial screening strategy to improve the early diagnosis and prevention of GC. METHODS: Oral contrast-enhanced trans-abdominal ultrasonography (OCTU) was initially applied to screen around 15,000 residents from 24 different rural villages of Changxing Island in Shanghai, China, facilitating the identification of high-risk population for further endoscopy examination. RESULTS: 176 subjects (1.18 %) were initially identified with gastric diseases using OCTU while 14,787 ones (98.93 %) were normal with negative results. 145 out of 176 individuals (82.39 %) took further endoscopy examination, and 16 were diagnosed with GC with biopsy examination, with 9 of them at the early stage. We followed up with the Center for Disease Control and Prevention, and identified another 6 GC cases occurred within one year among OCTU-negative population, serving as an adjustment factor for sensitivity analysis. As a result, with a total of 22 GC cases included in this cohort, the positive predictive rate, the negative predictive value, sensitivity, and specificity were 9.09％, 99.96 %, 75.5 %, and 98.93 %, respectively. CONCLUSIONS: OCTU is feasible, non-invasive, low-cost, and widely acceptable in rural area, thus we proposed that OCTU is practicable to serve as a supplementary screening method to improve the early detection of GC in rural area of China and other developing countries with large population.

[Emerging roles of Hippo signaling pathway in gastrointestinal cancers and its molecular mechanisms].

Hippo signaling pathway is highly conservative in evolution. MST1/2, LATS1/2, and the effector protein YAP/TAZ are the core members of this signaling pathway in mammalian cells. There have been many studies on YAP/TAZ and its downstream, however, the upstream regulatory factors of the Hippo signaling pathway remain unclear, and become one of the hot research directions of this pathway at present. In addition, Hippo signaling pathway can cross-talk with other signaling pathways such as Wnt and Notch signaling pathways, and plays an important role in controlling organ size, maintaining tissue homeostasis, and promoting tissue repair and regeneration. Abnormal Hippo signaling pathway may lead to the occurrence of a variety of tumors, especially gastrointestinal cancers such as liver cancer, colorectal cancer and gastric cancer. The abnormal expression of its members in gastrointestinal cancers is related to cancer cell proliferation, apoptosis, invasion and migration. Hippo signaling pathway is vital for liver repair and regeneration. Its inactivation will lead to the occurrence of primary liver cancer. The mechanism of YAP in liver cancer mainly depends on TEAD-mediated gene transcription. Hippo signaling pathway is also important for maintaining intestinal homeostasis, and its imbalance can lead to the occurrence and recurrence of colorectal cancer. In primary and metastatic gastric cancer, the expression of YAP/TAZ is significantly up-regulated, but the specific molecular mechanism is unclear. This article summarizes the recent progress on Hippo signaling pathway and its upstream regulatory factors, its roles in the development of gastrointestinal cancers and related molecular mechanisms; and also discusses the future research directions of Hippo signaling pathway.

[Correlation of behavioral performance with expressions of substance P and neurokinin-1 receptor in the L5－S2 spinal cord of chronic prostatitis rats].

OBJECTIVE: To investigate the correlation between the behavioral performance and the expressions of substance P (SP) and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5－S2 spinal cord in rats with chronic prostatitis (CP). METHODS: A CP model was made in 30 adult male SD rats by intraperitoneal injection of 0.5 ml dyphtheria pertussis tetanus (DPT) vaccine and mixed solution of 1 ml prostatein extract and complete adjuvant in a 1∶1 ratio, and another 10 rats were injected with the same volume of normal saline as controls. At 45 (n = 10), 60 (n = 10) and 90 days (n = 10) after modeling, the behavioral changes of the rats were observed by open-field and sucrose consumption tests, the prostatic indexes and levels of serum TNF-α, IL-1ß, IL-2 and IL-10 were obtained, and the expressions of SP and NK1-R in the L5－S2 spinal cord were determined by immunohistochemistry. RESULTS: Compared with the controls, the CP model rats showed obviously decreased horizontal and vertical movement scores and sucrose consumption, particularly in the 90 d group (P < 0.05), significantly reduced prostatic indexes in the 45 d, 60 d and 90 d groups (all P < 0.05), even lower in the 90 d than in the 45 d and 60 d groups (P < 0.05). Edema and lymphocytes were increased in the prostatic tissue with the prolonged time of modeling. The levels of serum TNF-α, IL-1ß, IL-2 and IL-10 were markedly elevated in all the CP rats as compared with those in the controls (P < 0.05), and so were the expressions of SP and NK-1R in the L5－S2 spinal cord (P < 0.05), even more significantly in the 90 d than in the 45 d and 60 d groups (P < 0.05). CONCLUSIONS: Rats with chronic prostatitis are characterized by behavioral manifestation of depression, increased levels of serum TNF-α, IL-1ß, IL-2 and IL-10, and a time-dependent upregulation of the expressions of SP and NK-1R in the posterior horn of the L5-S2 spinal cord, which suggests a correlation between the behavioral performance and the expressions of SP and NK-1R in the L5－S2 spinal cord of the rats.

Downregulation of PDCD4 by miR-21 suppresses tumor transformation and proliferation in a nude mouse renal cancer model.

Programmed cell death 4 (PDCD4) is known to suppress neoplastic transformation, cell proliferation and metastasis, and to be downregulated by microRNA-21 (miR-21) in renal cell carcinoma (RCC) cell lines and tissues. The aim of the present study was to investigate the roles of and association between PDCD4 and miR-21 in a nude mouse renal cancer model. A total of 24 BALB/c male nude mice were randomly assigned into the following three groups: Negative control (NC; n=8), miR-21 inhibitor (n=8) and miR-21 mimic (n=8). Subsequently, renal cell adenocarcinoma 786-O cells were subcutaneously transplanted into the armpits of the mice, which were then injected daily with NC small interfering (si)RNA, precursor-miR-21 (mimic) or anti-miR-21 (inhibitor). Tumors were removed from the mice and weighed 16 days following 786-O cell transplantation. In addition, the expression of miR-21 and PDCD4 mRNA in cancer tissues was analyzed using reverse transcription-quantitative PCR. The expression of PDCD4 protein in cancer tissues was also examined using immunohistochemistry and western blotting. Furthermore, 786-O cells were transfected with PDCD4 siRNA or NC siRNA, and the effects of silencing PDCD4 on tumor cell growth, proliferation and invasion were investigated using soft agar colony formation, EdU cell proliferation assay and Transwell migration and invasion assays. Another 16 BALB/c male nude mice were randomly assigned into two groups as follows: NC (n=8) and PDCD4 siRNA (n=8). The 786-O cells were subcutaneously transplanted into the armpits of the mice, which were subsequently injected daily with NC siRNA or PDCD4 siRNA. The tumors were removed and weighed 16 days following transplantation. Compared with the NC group, tumor weight in the miR-21 mimic group was significantly increased. By contrast, tumor weight in the miR-21 inhibitor group was significantly decreased. Similar to the results observed in human renal cancer tissue and cell lines, miR-21 expression in the nude mouse renal cancer models was significantly upregulated in the miR-21 mimic group compared with the NC group, while it was significantly lower in the miR-21 inhibitor group. Furthermore, there was a significant reduction in PDCD4 protein levels in the miR-21 mimic group and a significant increase in the miR-21 inhibitor group compared with the NC, whereas PDCD4 mRNA expression was not significantly altered. In the EdU proliferation assay, the mean percentage of new cells that incorporated EdU was 28.6% in the NC siRNA group and significantly increased to 44.7% in PDCD4 siRNA transfected cells. In the soft agar colony formation assay, Transwell and migration and invasion assays, a significant increase in colony formation, migration and invasion capacity in PDCD4 siRNA-transfected cells was observed compared with the NC. Furthermore, compared with the NC group, tumor weight in the PDCD4 siRNA group was significantly increased. Similar to the results observed in human renal cancer tissue and cell lines, miR-21 promoted cancer cell hyperplasia and proliferation, and post-transcriptionally downregulated PDCD4 protein expression, in the nude mouse renal cancer model. The results of the present study and previous studies indicate that PDCD4 and miR-21 serve an important role in renal cancer. Thus, increasing PDCD4 expression or inhibiting miR-21 expression may constitute effective novel therapeutic strategies for the treatment of renal cancer.