Ecological barriers: An approach to ecological conservation and restoration in China.

The Chinese government has pursued comprehensive ecological conservation and restoration by establishing an ecological barrier system. However, the majority of international research tends to focus on the connectivity between habitats, overlooking the functions that ecological barriers play in ecological conservation and restoration. The existing literature lacks a systematic exploration of the theory and practice of ecological barriers. This study employed the literature analysis tool CiteSpace to present the theoretical and developmental trends in ecological barriers from various perspectives, including research fields, historical evolution, research hotspots, and major research nations. By analyzing the differences in the understanding of ecological barriers between China and other countries, examining the ecological barriers construction history in China, and exploring the types and functions of ecological barriers, this study summarizes the framework of China's ecological barriers construction system as "features-functions-problems." Constructing an ecological barrier system can help achieve ecological conservation and restoration goals in China.

Segmentation of rectal tumor from multi-parametric MRI images using an attention-based fusion network.

Accurate segmentation of rectal tumors is the most crucial task in determining the stage of rectal cancer and developing suitable therapies. However, complex image backgrounds, irregular edge, and poor contrast hinder the related research. This study presents an attention-based multi-modal fusion module to effectively integrate complementary information from different MRI images and suppress redundancy. In addition, a deep learning-based segmentation model (AF-UNet) is designed to achieve accurate segmentation of rectal tumors. This model takes multi-parametric MRI images as input and effectively integrates the features from different multi-parametric MRI images by embedding the attention fusion module. Finally, three types of MRI images (T2, ADC, DWI) of 250 patients with rectal cancer were collected, with the tumor regions delineated by two oncologists. The experimental results show that the proposed method is superior to the most advanced image segmentation method with a Dice coefficient of [Formula: see text], which is also better than other multi-modal fusion methods. Framework of the AF-UNet. This model takes multi-modal MRI images as input, and integrates complementary information using attention mechanism and suppresses redundancy.

Long-Term Follow-Up Results of Adjuvant Intensity-Modulated Radiotherapy with Concurrent Paclitaxel and Cisplatin in High-Risk Endometrial Cancer Patients.

Purpose: The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Methods: Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. Results: A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage (P < 0.05). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Conclusion: Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.

The Role of Radiotherapy in the Treatment of Retroperitoneal Lymph Node Metastases from Colorectal Cancer.

PURPOSE: Retroperitoneal lymph node metastases are rare in colorectal cancer. Optimal treatment strategies are still unknown. PATIENTS AND METHODS: We retrospectively enrolled colorectal cancer patients who had received radiotherapy for retroperitoneal lymph node metastases from 2009 to 2018. Patients with isolated retroperitoneal lymph node metastases or retroperitoneal lymph nodes with extra-retroperitoneal metastases were all included. A median dose of 60 Gy was delivered. RESULTS: A total of 68 patients were enrolled in this study; 28 (41%) of them had extra-retroperitoneal metastases. In the isolated retroperitoneal lymph node metastases group, complete response was found in 5 patients (12.5%), partial response was achieved in 20 patients (50%), 9 patients (22.5%) had stable disease. The 1-, 2- and 3-year local control rates were 87.5%, 77.5%, and 70%. In the extra-retroperitoneal metastases group, the disease control rate was 75%, including complete response in 1 patient (3.6%), partial response in 4 patients (14.3%) and stable disease in 16 patients (57.1%). The 1-, 2- and 3-year local control rates were 57.1%, 42.8%, and 0%. The median overall survival was 59.4 months and 19 months in the isolated retroperitoneal lymph node metastases group and extra-retroperitoneal metastases group, respectively. In the isolated retroperitoneal lymph node metastases group, the 1-year and 3-year overall survival values were 90.2% and 75.8%, respectively. The 1-year and 3-year progression-free survival values were 57.9% and 0%, respectively. The extra-retroperitoneal metastases group experienced worse survival outcome (1-year overall survival: 57.9%, P<0.05; and 1-year progression-free survival: 22.5%, P<0.05). CONCLUSION: For patients with isolated retroperitoneal lymph node metastases, radiotherapy combined with systemic treatment can be used as a method to achieve no evidence of disease and can result in good local control and survival. For patients with extra-retroperitoneal metastases, although the survival is much worse than that of isolated retroperitoneal lymph node metastases, radiotherapy is an effective palliative treatment to relieve pain and obstruction based on systemic treatment.

Simvastatin Inhibits the Malignant Behaviors of Gastric Cancer Cells by Simultaneously Suppressing YAP and ß-Catenin Signaling.

BACKGROUND: Statins, which are used to lower blood cholesterol levels by inhibiting HMG-CoA reductase, have shown anticancer effects in many cancer cells. However, the role of statins in gastric cancer remains unclear. This study aims to investigate whether the statins could antagonize progression of gastric cancer cells and tried to find the molecule mechanism. METHODS: Effects of simvastatin on the morphology, proliferation, migration, apoptosis, and invasion of gastric cancer cells were detected and compared. Western blotting, cell viability assay, fluorescence, and transfection were employed to study the molecule mechanism of the effects and the interaction between YAP and ß-catenin signaling. RESULTS: Simvastatin could inhibit proliferation, migration and invasion, and promote the apoptosis in gastric cancer cells. Mechanistic studies showed that simvastatin treatment could inhibit the expression of ß-catenin and the activity of YAP and the downstream targets of YAP and ß-catenin in gastric cancer cells. Moreover, we found that YAP and ß-catenin could form a positive feedback loop in gastric cancer cells. Further investigation revealed that simvastatin mainly acted through by inhibiting the activity of RhoA to inhibit YAP and ß-catenin, and the geranylgeranyl pyrophosphate pathway mediated this regulation. CONCLUSION: Statins represent a promising therapeutic option for gastric cancer by simultaneously targeting YAP and ß-catenin signaling.

Quantifying Reoxygenation in Pancreatic Cancer During Stereotactic Body Radiotherapy.

Hypoxia, the state of low oxygenation that often arises in solid tumours due to their high metabolism and irregular vasculature, is a major contributor to the resistance of tumours to radiation therapy (RT) and other treatments. Conventional RT extends treatment over several weeks or more, and nominally allows time for oxygen levels to increase ("reoxygenation") as cancer cells are killed by RT, mitigating the impact of hypoxia. Recent advances in RT have led to an increase in the use stereotactic body radiotherapy (SBRT), which delivers high doses in five or fewer fractions. For cancers such as pancreatic adenocarcinoma for which hypoxia varies significantly between patients, SBRT might not be optimal, depending on the extent to which reoxygenation occurs during its short duration. We used fluoro-5-deoxy-α-D-arabinofuranosyl)-2-nitroimidazole positron-emission tomography (FAZA-PET) imaging to quantify hypoxia before and after 5-fraction SBRT delivered to patient-derived pancreatic cancer xenografts orthotopically implanted in mice. An imaging technique using only the pre-treatment FAZA-PET scan and repeat dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans throughout treatment was able to predict the change in hypoxia. Our results support the further testing of this technique for imaging of reoxygenation in the clinic.

Inhibition of YAP reverses primary resistance to EGFR inhibitors in colorectal cancer cells.

Mutant KRAS and BRAF are associated with primary EGFR inhibitor resistance in colorectal cancer (CRC). However, other biomarkers that could predict EGFR inhibitor resistance remain elusive. In the present study, immunoblotting and cell proliferation results revealed that yes­associated protein (YAP), a downstream effector of the Hippo pathway, was positively associated with primary cetuximab resistance in CRC cells. YAP knockdown enhanced the cytotoxicity of cetuximab in CRC cells. Simvastatin, a 3­hydroxy­3­methylglutaryl­coenzyme A (HMG­CoA) reductase inhibitor of the mevalonate pathway that inhibits YAP bioactivity through nuclear translocation and total YAP expression, increased the cytotoxicity of EGFR inhibitors (cetuximab and gefitinib) against CRC cells. The combination of simvastatin and EGFR inhibitors inhibited YAP and EGFR signaling more markedly than each agent alone. Adding back geranylgeranyl pyrophosphate (GGPP), a key product of the mevalonate pathway, reversed the YAP bioactivity inhibition induced by simvastatin and the cell proliferation inhibition induced by the combination of simvastatin and EGFR inhibitors. Collectively, these results revealed that YAP may be useful in identifying cetuximab resistance in CRC and indicated that targeting of both YAP and EGFR signals may present a promising therapeutic approach for CRC.

Clinical significance of circulating tumor cells in gastric cancer patients.

Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the blood stream that are thought to have a key role in cancer metastasis. Investigation of CTCs is an exciting area of research but remains in its infancy, and the presence of CTCs has been associated with worse prognosis in several major cancer types. Gastric cancer (GC) is a highly lethal malignancy and a serious public health concern in East Asia especially in China. There is an urgent need for identifying new, better prognostic markers to enhance diagnosis and prognosis, facilitate drug development, and to improve the treatment of gastric cancer patients. There are considerable interests in gastric CTCs given their potential use as gastric cancer biomarkers. This review highlights recent advances in studies of gastric CTCs, including the isolation and biological molecular characteristics of gastric CTCs, and their clinical significance.

The Rho GTPase RhoE is a p53-regulated candidate tumor suppressor in cancer cells.

Previous studies have shown that RhoE, an atypical member of the Rho GTPase family, may play an opposite role to RhoA in regulating cell proliferation and invasion. To explore the relationship between RhoE and the malignant phenotypes of human cancer, we have determined the expression patterns of RhoE in varying grade of human cancer tissues and tested the effects of RhoE expression in several RhoE underexpressing cancer cell lines. Systemic immunocytochemistry analyses of gastric, colorectal, lung and breast carcinomas, respectively, showed that RhoE protein expression was significantly decreased in most cancer cases compared with that of adjacent normal tissues. Enhanced RhoE expression could markedly inhibit proliferation, migration and invasion and induce apoptosis of the cancer cells which have relatively low levels of endogenous RhoE expression. Wild-type p53 (wt-p53) could strongly increase RhoE expression in p53-transfected cells. Furthermore, the luciferase assays indicated that wt-p53 significantly enhanced the activities of RhoE promoter compared with mutant p53 (mt-p53) in PC3 cells (p53 null). Collectively, data are presented showing that RhoE may participate in human cancer progression and act as a candidate target of p53, and these findings also strongly suggest that RhoE may be a new candidate tumor suppressor and could serve as a potential target in the gene therapy of cancer.

A distinct role of RhoB in gastric cancer suppression.

Although Rho family GTPases RhoA, RhoB and RhoC share more than 85% amino acid sequence identity, they may play distinct roles in tumor progression. RhoA and RhoC have been suggested to have positive effects on tumor progression, but the role of RhoB in cancer, particularly in gastric cancer, remains unclear. In our study, we have examined the expression levels of these three Rho GTPases in a large panel of specimens from gastric cancer patients by immunohistochemistry. We found that RhoA and RhoC expression were significantly elevated, while RhoB was reduced or absent, in surgically removed gastric cancer tissues when compared to normal gastric tissues. The significant reduction of RhoB expression was confirmed in another group of gastric cancer samples in comparison to the adjacent non-neoplastic tissues. Then we transfected the plasmids containing RhoA, RhoB or RhoC cDNA into two gastric cancer cell lines, SGC7901 and AGS cells, respectively. By overexpression experiments, we found that RhoA promoted the gastric cancer cell proliferation and RhoC stimulated migration and invasion of the cancer cell. RhoB expression, however, significantly inhibited the proliferation, migration and invasion of the gastric cancer cells and also enhanced the chemosensitivity of these cells to anticancer drugs. It appears that RhoB plays an opposing role from that of RhoA and/or RhoC in gastric cancer cells. Our work suggests that RhoB may play a tumor suppressor role and subsequently may have potential implications in future targeted therapy.

miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells.

miRNAs have emerged as post-transcriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Cdc42, one of the best characterized members of the Rho GTPase family, is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. In the present study, we have identified miR-137 as a potential regulator of Cdc42 expression. A bioinformatics search revealed a putative target-site for miR-137 within the Cdc42 3' UTR at nt 792-798, which is highly conserved across different species. Expression of miR-137 in colorectal cancer cell lines was found inversely correlated with Cdc42 expression. miR-137 could significantly suppress Cdc42 3' UTR luciferase-reporter activity, and this effect was not detectable when the putative 3' UTR target-site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced both mRNA and protein expression levels of Cdc42 and mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest, and blocking invasion of the colorectal cancer cells, whereas anti-miR-137 expression led to the opposite effect. Furthermore, expression of miR-137 suppressed the immediate downstream effector of Cdc42, PAK signaling. Our results suggest that miR-137 may have a tumor suppressor function by directly targeting Cdc42 to inhibit the proliferation and invasion activities of colorectal cancer cells. They raise an interesting possibility that Cdc42 activity and function can be controlled by miRNAs in addition to the classic regulators such as guanine nucleotide exchange factors and GTPase-activating proteins.

[Analysis of the P53 transcriptional activity in gastric cancer].

OBJECTIVE: To investigate the transcriptional activity of P53 in gastric cancer. METHODS: The activity of p53 in gastric cancer was investigated by dual-luciferase reporter assay. The coding sequence of the p53 was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced. The expression of P21WAF1/Cip1, Gadd45alpha and Mdm2 was detected by immunohistochemistry in 76 samples of gastric carcinoma, and their adjacent tissues were analyzed as control. RESULTS: The p53 activity was higher in human normal cell lines than that of gastric cancer. Furthermore, the transcriptional activity of P53 was lowest in MKN28 cells in which p53 was mutated. The expression level of P21WAF1/Cip1, Gadd45alpha and Mdm2 in the adjacent tissues was higher than that of cancer tissues (P<0.05), and there was a tendency of decline in the positive ratio with the poor differentiation of the carcinoma (P<0.05). In addition, a strong linear correlation was observed between P21WAF1/Cip1, Gadd45alpha and Mdm2 (P<0.05). CONCLUSION: Changes of P53 transcriptional activity play an important role in the development of gastric cancer. p53 mutation could affect its transcriptional activity. P21WAF1/Cip1, Gadd45alpha and Mdm2 are a group of effecters that could reflect P53 transcriptional activity when detected together in cancer tissues.

[Cultivation and characterization of tumor spheres generated from human colorectal cancer cell lines].

OBJECTIVE: To study on the cultivation method for tumor spheres from colorectal cancer cell lines and identify whether resulting Colo205 spheroid cells display cancer stem cell characteristics. METHODS: Lovo, Colo205 and SW480 cells were seeded in serum free medium (SFM) with EGF and bFGF. Flow cytometry analysis, cell invasion assay and xenograft experiment were applied to examine the cell surface marker expression pattern, cell invasive ability and in vivo tumorigenicity of both Colo205 spheres and parental cells. CD44 expression of tumor spheroid cells was also analyzed after cultured with serum supplemented medium by flow cytometry. CD44, Musashi-1 and Oct4 mRNA were detected in these two cells by RT-PCR. RESULTS: Tumor spheres could be generated from three colorectal cancer cell lines in SFM. The formation and proliferation of tumor spheres were benefited from fresh SFM, cell dissociation reagent Accutase and the floating status of cancer cells. The overwhelming majority of spheroid cells were CD44+ cells. But CD44+ cells were gradually decreased when spheres cultured with serum supplemented medium. Colo205 spheres have higher Musashi-1 and Oct4 mRNA expression, tumor-initiating capability and invasive ability compared with those of parental cells. CONCLUSION: Tumor spheres in which enrich cancer stem cells can be generated and matained from colorectal cancer cell lines in SFM on floating-culture condition.

[The effect of Rac1 siRNA on the biological behaviors of gastrointestinal cancer cells].

OBJECTIVE: To explore the effect of Rac1 siRNA on the expression of Rac1 and the biological behaviors of gastrointestinal cancer cells. METHODS: Rac1 siRNA was transfected into human gastric cancer cell line SGC803 and colorectal cancer cell line Lovo by lipofectamine 2000. The expression of Rac1 in these cell lines were detected by Western blot and RT-PCR after 48 hours of the transfection. The effect of Rac1 on the proliferation of human gastric cancer cell line SGC803 and colorectal cancer cell line Lovo were tested by CCK8 kit. The motility of the transfected and the control cancer cells were assessed by Wound-healing assay and invasion assay. The apoptotic index was evaluated by Hoechst 33258 staining and FCM. RESULTS: Rac1 siRNA can down-regulated the expression of Rac1 on human gastric cancer cell line SGC803 and colorectal cancer cell line Lovo remarkably, and Rac1 siRNA can inhibit both the proliferation and motility of the transfectants. Analysis of apoptosis demonstrated that Rac1 siRNA can promote apoptosis of the gastric cancer cells and colorectal cancer cells. CONCLUSION: Rac1 play an important role in the regulation of biological behaviors of human gastric cancer and colorectal cancer cells, and the interference of Rac1 expression could provide a novel path in reversing the malignant phenotypes of these malignancies.

[Expression of RhoE in lung and breast cancer and its clinical significance.].

BACKGROUND: Rho family is closely related with the growth , differentiation and metastasis of tumer cells. The objective of this work is to investigate the expression of RhoE in lung and breast carcinoma and their corresponding adjacent tissues, as well as its relationship between the expression and clinical pathological grades. The results of this study provide evidences for exploring the biological functions and clinical significance of RhoE. METHODS: The expression of RhoE was detected by immunohistochemistry in 62 lung carcinoma samples and 34 breast carcinoma samples, and their corresponding adjacent tissues were taken as control. RESULTS: RhoE was generally expressed in normal tissues, but the expression level of RhoE in carcerous tissues was decreased or absent. The stained value of breast carcinoma was 3.65+/-0.62, but the adjacent cancerous tissues was 10.53+/-0.44, significantly higher than that of the adjacent cancerous tissues (t=12.402, P<0.001). While the stained value of lung carcinoma was 2.19+/-0.19, lower than that of the adjacent cancerous tissues (4.11+/-0.24, t =7.123, P<0.005). Moreover, there is a declining tendency of the stained value as the poor differentiation of the carcinoma (Chi-Square=26.536, P<0.005). CONCLUSIONS: The expression of RhoE in carcerous tissues was remarkbaly decreased. Considering the recent research achievement and our early experimental results about RhoE, we inferred that RhoE may play a negative role in the development and progression of lung and breast carcinoma. So further research on RhoE would provide a new target for the molecular targeting therapy of cancer.