LncRNA PCED1B-AS1 mediates miR-3681-3p/MAP2K7 axis to promote metastasis, invasion and EMT in gastric cancer.

BACKGROUND: LncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer. METHODS: TCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice. RESULTS: PCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells. CONCLUSION: PCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.

Finely manipulating room temperature phosphorescence by dynamic lanthanide coordination toward multi-level information security.

Room temperature phosphorescence materials have garnered significant attention due to their unique optical properties and promising applications. However, it remains a great challenge to finely manipulate phosphorescent properties to achieve desirable phosphorescent performance on demand. Here, we show a feasible strategy to finely manipulate organic phosphorescent performance by introducing dynamic lanthanide coordination. The organic phosphors of terpyridine phenylboronic acids possessing excellent coordination ability are covalently embedded into a polyvinyl alcohol matrix, leading to ultralong organic room temperature phosphorescence with a lifetime of up to 0.629 s. Notably, such phosphorescent performance, including intensity and lifetime, can be well controlled by varying the lanthanide dopant. Relying on the excellent modulable performance of these lanthanide-manipulated phosphorescence films, multi-level information encryption including attacker-misleading and spatial-time-resolved applications is successfully demonstrated with greatly improved security level. This work opens an avenue for finely manipulating phosphorescent properties to meet versatile uses in optical applications.

Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.

BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.

IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer.

Emerging evidence has indicated the aberrant expression of PIWI-interacting RNAs (piRNAs) in human cancer cells to regulate tumor development and progression by governing cancer cell stemness. Herein, we identified downregulation of piR-2158 in human breast cancer tumors, especially in ALDH+ breast cancer stem cells (BCSCs) from patients and cell lines, which was further validated in two types of genetically engineered mouse models of breast cancer (MMTV-Wnt and MMTV-PyMT). Enforced overexpression of piR-2158 in basal-like or luminal subtypes of breast cancer cells suppressed cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness in vitro. Administration of a dual mammary tumor-targeting piRNA delivery system in mice reduced tumor growth in vivo. RNA-seq, ChIP-seq and luciferase reporter assays demonstrated piR-2158 as a transcriptional repressor of IL11 by competing with AP-1 transcription factor subunit FOSL1 to bind the promoter of IL11. STAT3 signaling mediated piR-2158-IL11 regulation of cancer cell stemness and tumor growth. Moreover, by co-culturing of MDA-MB-231 and HUVECs in vitro and CD31 staining of tumor endothelial cells in vivo, we demonstrated inhibition of angiogenesis by piR-2158-IL11 in breast cancer. In conclusion, the current study not only reveals a novel mechanism through which piR-2158 inhibits mammary gland tumorigenesis via regulating cancer stem cells and tumor angiogenesis, but also provides a novel therapeutic strategy in treatment of breast cancer.

Derivatization of sumanenetrione through Lewis acid-mediated Suzuki-Miyaura coupling and an unprecedented ring opening.

A series of sumanenetrione derivatives were synthesized through Lewis acid-mediated Suzuki-Miyaura cross-coupling. Their optical properties reflected the significantly strong electron-accepting ability of sumanenetrione. The bowl strain of the 2-hydroxyphenyl derivative brought the ring-opening response adjacent to the substituent even at room temperature without any activation, which generally requires harsh conditions.

Superficial Flat-Type Early-Stage Gastric Signet Ring Cell Carcinoma in the Atrophic Background Mucosa: Two Case Reports.

OBJECTIVES: Gastric signet ring cell carcinoma is a rare and highly malignant adenocarcinoma, which is characterized by early metastasis, rapid progression and poor prognosis. Several studies have shown that early-stage gastric signet ring cell carcinoma may have equal or better prognosis than other types of gastric cancer. However, most of the early-stage lesions are difficult to detect by endoscopy. We aim to illustrate the difficulty of early detection of gastric signet ring cell carcinoma with mucosal atrophy. METHODS: The endoscopic and pathological features of two female cases were analyzed by upper gastrointestinal white light endoscopy combined with narrow-band imaging and endoscopic biopsy. RESULTS: Two female cases were diagnosed with early-stage gastric signet ring cell carcinoma with atrophic background mucosa occurring in the middle and lower part of the stomach. Both lesions less than 2.0 cm in diameter were surgically removed and identified as intramucosal adenocarcinoma. CONCLUSION: We can roughly identify the demarcation of the lesion by combining white light endoscopy and narrow-band imaging, and slightly irregular microsurface and microvascular pattern of the lesion were found via magnifying endoscopic observation, but the demarcation can hardly be accurately identified.

Detection of Circulating Tumor DNA Methylation in Diagnosis of Colorectal Cancer.

INTRODUCTION: Emerging evidence has demonstrated the potential of the circulating tumor DNA (ctDNA) methylation in the application of cancer diagnosis. METHODS: Three genes including Septin9, Syndecan-2 (SDC2), and branched-chain amino acid transaminase 1 (BCAT1), which have been well demonstrated to have aberrant expression in colorectal cancer (CRC) as tumor suppressors, were selected for detection. A total of 234 peripheral plasma samples from 104 patients with CRC and 130 patients with colorectal polyps, and 60 plasma samples from healthy controls, were collected before any treatment. A real-time polymerase chain reaction-based gene panel was used to detect the methylation of Septin9, SDC2, and BCAT1. The composite score (P) was calculated according to the cycle threshold values of the 3 methylated genes using the logistic regression equation. RESULTS: The ctDNA methylation of the 3 genes had a significantly higher level in patients with CRC, compared with patients with colorectal polyps and healthy controls. The composite score (P) showed association with tumor stages in CRC but not with the tumor location (colon or rectum). In addition, BCAT1 and Septin9 showed better performance for CRC diagnosis, by which CRC was able to distinguish from polyps with sensitivity of 83.7%, specificity of 93.9%, and area under the curve of 0.908. The diagnostic efficiency was significantly improved by combining composite score (P), carcinoembryonic antigen, and fecal immunochemical test for hemoglobin (area under the curve = 0.962). DISCUSSION: The composite score (P) derived from the ctDNA methylation levels of Septin9, SDC2, and BCAT1 can be used for CRC diagnosis with high sensitivity and high specificity. A combination of ctDNA methylation, carcinoembryonic antigen, and fecal immunochemical test for hemoglobin was proved to be the most effective approach to diagnose CRC.

A Novel Multiparameter Scoring Model for Noninvasive Early Prediction of Ischemic Colitis: A Multicenter, Retrospective, and Real-World Study.

INTRODUCTION: Ischemic colitis (IC) is a common gastrointestinal ischemic disease caused by hypoperfusion or reperfusion injury. However, there are few studies on risk factors associated with poor prognoses of the disease. This study aimed to determine the predictors of poor prognoses in patients with IC and establish a prognostic scoring method with good internal and external validity for identifying severe cases in an early stage. METHODS: We established a prognosis model by conducting a multicenter, retrospective study of patients hospitalized with IC between November 2008 and May 2020. Predictive power was tested using 5-fold internal cross-validation and external validation. RESULTS: The following 6 factors were included in the prognostic model: neutrophil count, D-dimer level, ischemia of the distal ileum, ischemia of the hepatic flexure, ulceration, and luminal stenosis. The area under the receiver-operating characteristic curve for internal cross-validation of the prediction model was 86%, and that for external validation was 95%. During internal validation, our model correctly identified 88.08% of the patients. It was further found that patients younger than 65 years with a higher neutrophil-to-lymphocyte ratio and higher heart rate had poor prognoses. Patients aged 65 years and older with ischemia of terminal ileum, hepatic flexure, splenic flexure, and intestinal stenosis had poor prognoses. DISCUSSION: Patients with ischemia in the hepatic flexure and the distal ileum, endoscopic evidence of ulcer or stenosis, higher neutrophil counts, and higher D-dimer levels have worse prognoses. This information could aid in the selection of timely and appropriate treatment.

Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer.

Colorectal cancer is the leading cause of death from cancer globally. The current treatment protocol still heavily relies on early detection and surgery. The molecular mechanisms underlying development of colorectal cancer are clinically important and determine the prognosis and treatment response. The arginine metabolism pathway is hyperactive in colorectal cancer and several molecules involved in the pathway are potential targets for chemoprevention and targeted colorectal cancer therapy. Endothelial nitric oxide synthase (eNOS), argininosuccinate synthetase and ornithine decarboxylase (ODC) are the main enzymes for arginine metabolism. Limiting arginine-rich meat consumption and inhibiting ODC activity largely reduces polyamine synthesis and the incidence of colorectal cancer. Arginine transporter CAT-1 and Human member 14 of the solute carrier family 6 (SLC6A14) are overexpressed in colorectal cancer cells and contributes to intracellular arginine levels. Human member 9 of the solute carrier family 38 (SLC38A9) serves as a component of the lysosomal arginine-sensing machinery. Pharmaceutical inhibition of single enzyme or arginine transporter is hard to meet requirement of restoring of abnormal arginine metabolic network. Apart from application in early screening for colorectal cancer, microRNA-based therapeutic strategy that simultaneously manipulating multiple targets involved in arginine metabolism brings promising future in the treatment of colorectal cancer.

Nomogram for predicting the feasibility of natural orifice specimen extraction after laparoscopic rectal resection.

BACKGROUND AND AIM: The goal of this study was to develop a preoperative nomogram for predicting the feasibility of trans-anal natural orifice specimen extraction (NOSE) for rectal cancer. METHODS: The analysis included 201 patients who underwent trans-anal NOSE and 457 patients who failed to undergo trans-anal NOSE in Shanghai East Hospital. The data collected included age, gender, body mass index, presence of tumor obstruction, distance from anal verge; maximum tumor diameter and anteroposterior thickness of mesorectum (AP) measured by magnetic resonance imaging; interspinous diameter, intertuberous diameter (IT), anteroposterior diameter of the inlet (API), anteroposterior diameter of the midplane, anteroposterior diameter of the outlet (APO), sacral length and pelvic depth (PD) measured by computed tomography. RESULTS: The multivariate analysis suggested that a lower body mass index (P < 0.001), no tumor obstruction (P = 0.005), a shorter distance from anal verge (P < 0.001), a smaller tumor size (P < 0.001), a thinner AP (P < 0.001), a wider and shallower bony pelvis (API/PD, P < 0.001), and a wider and shorter pelvic outlet (IT/APO, P < 0.001) were significantly associated with an increased probability of trans-anal NOSE. Successful NOSE patients had a decreased time to liquid intake (P < 0.001), a shorter postoperative hospital stay (P < 0.001), and fewer wound infections (P = 0.045). No significant difference in the rate of mortality or recurrence was observed. The nomogram model presented an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.78 to 0.85) and good calibration. CONCLUSION: We developed a nomogram model that has some predicative value for the feasibility of laparoscopic rectal resection with trans-anal NOSE, utilizing clinical and radiologic parameters, available in most institutions.

Starvation stress attenuates the miRNA-target interaction in suppressing breast cancer cell proliferation.

BACKGROUND: Emerging evidence has demonstrated the limited access to metabolic substrates as an effective approach to block cancer cell growth. The mechanisms remain unclear. Our previous work has revealed that miR-221/222 plays important role in regulating breast cancer development and progression through interaction with target gene p27. RESULTS: Herein, we determined the miRNA-mRNA interaction in breast cancer cells under induced stress status of starvation. Starvation stimulation attenuated the miR-221/222-p27 interaction in MDA-MB-231 cells, thereby increased p27 expression and suppressed cell proliferation. Through overexpression or knockdown of miR-221/222, we found that starvation-induced stress attenuated the negative regulation of p27 expression by miR-221/222. Similar patterns for miRNA-target mRNA interaction were observed between miR-17-5p and CyclinD1, and between mR-155 and Socs1. Expression of Ago2, one of the key components of RNA-induced silencing complex (RISC), was decreased under starvation-induced stress status, which took responsibility for the impaired miRNA-target interaction since addition of exogenous Ago2 into MDA-MB-231 cells restored the miR-221/222-p27 interaction in starvation condition. CONCLUSIONS: We demonstrated the attenuated interaction between miR-221/222 and p27 by starvation-induced stress in MDA-MB-231 breast cancer cells. The findings add a new page to the general knowledge of negative regulation of gene expression by miRNAs, also demonstrate a novel mechanism through which limited access to nutrients suppresses cancer cell proliferation. These insights provide a basis for development of novel therapeutic options for breast cancer.

Clinical efficacy and quality of life after transrectal natural orifice specimen extraction for the treatment of middle and upper rectal cancer.

BACKGROUND: Laparoscopic anterior resection with natural orifice specimen extraction (NOSE) avoids extra abdominal extraction incision during colorectal surgery. Some surgeons realized the benefits of NOSE on clinical efficacy. We compared the clinical efficacy of laparoscopic NOSE, laparoscopic non-NOSE and open surgery (OS) for short-term recovery and quality of life (QoL). METHODS: A single randomized controlled trial of NOSE for middle and upper rectal cancer between April 2014 and February 2018. Preoperative and postoperative clinical variables were analyzed and compared between the groups. Preoperative and 6 months postoperative QoL was assessed with the SF-36 QoL questionnaire. RESULTS: A total of 378 patients were enrolled, 334 patients randomly divided into NOSE group (n=104), non-NOSE group (n=119), OS group (n=111). The NOSE group was superior to the other two groups on the QoL after surgery. The NOSE group had the lowest postoperative VAS score between three groups. The postoperative time for bowel function recovery and the length of hospital stay was statistically significantly different among the three groups, with the NOSE group having the shortest time. The incidence of postoperative complications was lower in the NOSE group (12/104, 11.5%) than in the non-NOSE group (20/119, 16.8%), the difference was statistically significant. The Kaplan-Meier (K-M) survival curve showed no statistically significant difference in the disease-free survival (DFS) rate between the three groups. CONCLUSIONS: Comparing NOSE to non-NOSE and OS, the NOSE had significantly better functional recovery and better QoL. The NOSE group had a significant lower surgical complication rate than the non-NOSE group.

Post-synthesis strategy to integrate porphyrinic metal-organic frameworks with CuS NPs for synergistic enhanced photo-therapy.

Multifunctional nanotheranostic systems with both therapeutic and imaging functions are highly desired for the development of more effective and less toxic anti-tumor drugs. Herein, a simple but effective method is reported to fabricate a novel PCN-CuS-FA-ICG-based nanoplatform for dual-modal imaging-guided synergistic photothermal/photodynamic therapy. Porphyrinic metal-organic frameworks with CuS NPs are obtained in aqueous solution via a simple post-synthesis strategy. Furthermore, to obtain a more effective therapy, indocyanine green (ICG) was incorporated into the multifunctional theranostic platform to promote the photothermal therapeutic effect. The as-prepared PCN-CuS-FA-ICG not only exhibits an excellent 1O2 generation efficiency under 650 nm irradiation to achieve remarkable photodynamic cell killing, but also presents outstanding photothermal conversion under 808 nm irradiation to destroy tumor tissues by hyperthermia. In particular, the nanotherapeutic agent realized fluorescence and thermal imaging dual-modal imaging-guided cancer treatment. Meanwhile, in vivo experiments confirmed the evident accumulation of nanoparticles (NPs) at local tumors, and tumor growth was inhibited obviously via synergistic photothermal/photodynamic therapy with negligible side effects.

[Feasibility analysis on 3D laparoscopic surgery via transrectal extraction of specimens without abdominal incision in the treatment of slow transit constipation].

OBJECTIVE: To investigate the safety and feasibility of 3D laparoscopic surgery via transrectal extraction of specimens without abdominal incision in the treatment of slow transit constipation (STC). METHODS: From May 2015 to January 2017, 8 STC patients (6 females and 2 males) with informed consent were selected to receive subtotal colectomy with 3D laparoscopy as the no-incision incision group, in which the initial part of ascending colon and rectum were end-to-end anastomosed directly after extraction of the specimen through the rectum. Twelve STC patients (9 females and 3 males) undergoing traditional subtotal colectomy with 3D laparoscopy were selected as the traditional group by case matching method (gender, age, BMI, the difference of receiving operation time less than 12 months, same surgeon team). Perioperative parameters (operation duration, intraoperative blood loss, exhausting time, postoperative hospital stay, complications, postoperative pain score and additional pain management), inflammation index at postoperative day 1 and day 3 (leukocyte, procalcitonin, interleukin 6, C-reactive protein), postoperative peritoneal infection, wound healing, short-term and long-term efficacy, patient satisfaction evaluation (subjective hundred-mark system) at postoperative one year were compared between two groups. RESULTS: There were no significant differences between two groups in operation duration, intraoperative blood loss, exhausting time, postoperative hospital stay and morbidity of complication (all P>0.05). Significantly lower pain scores at postoperative 6-hour (median 3.0 vs. 4.5, U=23.0, P=0.042), lower ratio of additional analgesic at postoperative day 1(1/8 vs. 7/12, P=0.040) were found in the no-incision group. Leukocyte level at postoperative day 1 was significantly lower in the no-incision group [(11.0±3.5)×109/L vs. (14.7±3.6)×109/L, t=-2.281, P=0.035]. C-reactive protein concentration at postoperative day 3 was not significantly different between two groups but with different trend [median 78.1(0.1 to 154.0) mg/L vs. 22.0 (7.0 to 55.9) mg/L,U=33.0, P=0.047]. There were no significant differences of interleukin-6 and procalcitonin between two groups(all P>0.05). All the patients had follow-up for 14-31 months. Subjective effectiveness score was 90±9 in the no-incision group and 94±6 in the traditional group without significant difference(t=-1.099, P=0.286). No long-term complications associated with abdominal infection was observed in the no-incision group. CONCLUSION: 3D laparoscopic subtotal colectomy via transrectal extraction of specimens without abdominal incision in the treatment of STC has similar short-term and long-term efficacies compared with traditional laparoscopic assisted surgery, and does not increase the probability of abdominal contamination.

[Protective measures in laparoscopic resection for upper or mid rectal cancer and sigmoid colon cancer with transrectal specimen extraction surgery].

OBJECTIVE: To introduce the use of a self-made specimen protective sleeve in laparoscopic resection for upper or mid rectal cancer and sigmoid colon cancer with transrectal specimen extraction surgery and the improvement of implantation method, so as to avoid and reduce bacterial contamination and tumor cell dissemination in abdominal cavity. METHODS: During June 2015 and May 2017, 48 cases of high located rectal or sigmoid colon cancer were operated laparoscopically with natural orifices specimen extraction surgery (NOSES) using a self-made specimen protecting sleeve. Operation indication: (1) Rectum and sigmoid colon cancer with the distance of more than 6 cm from tumor inferior margin to dentate line. (2) The maximum diameter of intestine together with mesangial and tumor <7 cm by intraoperative judgment. (3) No anal and distal rectal surgery, no anorectal stenosis or lack of expansion capacity caused by trauma. (4) No ulcerative colitis, Crohn's disease or radiation proctitis. After transecting the rectum, the specimen protective sleeve was inserted through the right lower 12 mm main Trocar (This sleeve was tailored from the laparoscopic protective sleeve produced by China 3L Corporation, which was intercepted with 25-35 cm from one end of the sleeve according to the length of distal rectal retention. One end was ligated and the other was open with a ligature band. About 5 ml paraffin oil was used to rinse and lubricate during the operation). The rectal stump retained 7-8 cm in abdominal cavity. The transanal ligation part of the protective sleeve was cut off, then the stapler nail seat was inserted and specimen was pull out through the sleeve and rectum. RESULTS: There were 30 males and 18 females. The average age was (64.5±14.1) years, the BMI was (25.4±3.9) kg/m2, the tumor diameter was (3.3±1.1) cm, the maximum diameter of specimen was (5.4±1.5) cm and the length of specimen was (18.6±4.3) cm. Among these 48 cases, specimens of 36 patients were pulled out through inside of the sleeve easily, while specimens of 12 patients were quite difficult with resistance. Of 12 cases, 7 needed the help of transverse forceps, 4 needed to make 1 cm incision in pull-through bowel and insert a suction to decrease the volume of large specimens with gathering of gas and fluid, and 1 received small abdominal incision to remove specimen and perform intestinal reconstruction due to big specimen (the diameter of tumor and mesentery was 7.5 cm). Specimen tears of 6 patients didn't result in dissemination thanks to the specimen protecting sleeve. The operation time was (113.2±76.1) min, the bleeding amount was (38.5±17.3) ml, the time to first oral intake was (47.9±4.4) h, and the postoperative hospitalization length was (8.5±1.7) d. Anastomotic leakage occurred in 1 case (2.1%). No intra-abdominal and trocar infection, and obstruction were found. CONCLUSION: The use of protective sleeve and the improvement of the method of intraperitoneal implantation can effectively reduce the abdominal contamination during the specimen extraction. It can be applied to big specimens as well.

[Strategy and technique for simultaneous resection of rectal cancer and liver metastasis].

Rectal cancer with simultaneous liver metastasis is very common clinically. R0 surgical resection both for the original and metastatic tumor can achieve much better long-term oncological results. The operation types include traditional open procedures for both rectal cancer and liver metastatic resection; combination of laparoscopic resection of the rectal cancer and open procedure resection of the liver metastatic lesion; traditional laparoscopic-assisted rectal and liver metastatic tumor resection with small abdominal incision and total laparoscopic natural orifice specimen extraction surgery(NOSES) without abdominal incision. Due to the complexity of rectal anatomy and treatment strategy, leading to the difference from colon cancer with liver metastasis, and due to the effect of laparoscopic treatment, especially the 3D laparoscopy, patient selection for simultaneous resection should be well planned and individualized by surgeons based on conditions of themselves and patients.

STK31 as novel biomarker of metastatic potential and tumorigenicity of colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is the fifth most common cause of cancer deaths in China and fourth worldwide. Metastatic dissemination of primary tumors is considered main cause for CRC related mortality. The serine-threonine kinase 31 (STK31) gene is a novel cancer testis (CT) antigen. It was found significantly highly expressed in gastrointestinal cancers. In our study we aimed to analyze the correlation between STK31 expression patterns and metastasization, tumor stage and grade in CRC patients. RESULTS: Relative STK31 expression level was significantly higher in patients with lymph node metastasis. STK31 expression levels in primary tumorous tissues of metastatic patients were significantly higher than in ANCTs and in lymph nodes samples, both at the RNA level and the protein level. MATERIALS AND METHODS: Surgical specimens of cancerous tissues, paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with different clinicopathological features were collected. Expression of STK31 was detected and measured by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). CONCLUSIONS: Our data suggest that STK31 might be a potential biomarker in detecting, monitoring and predicting the metastatic risk of colorectal cancer.

Novel curcumin-loaded human serum albumin nanoparticles surface functionalized with folate: characterization and in vitro/vivo evaluation.

Folate-conjugated, curcumin-loaded human serum albumin nanoparticles (F-CM-HSANPs) were obtained by the chemical conjugation of folate to the surface of the curcumin (CM)-loaded human serum albumin nanoparticles (NPs). The NPs were characterized by various parameters, including size, polydispersity, zeta potential, morphology, encapsulation efficiency, and drug release profile. The mean particle size of F-CM-HSANPs was 165.6±15.7 nm (polydispersity index <0.28), and the average encapsulation efficiency percentage and drug loading percentage of the F-CM-HSANPs were 88.7%±4.8% and 7.9%±0.4%, respectively. Applied in vitro, the CM NPs, after conjugation with folate, maintained sustained release, and a faster release of CM was more visibly observed than the unconjugated NPs. F-CM-HSANPs can prolong the retention time of CM significantly in vivo. However, after intravenous injection of F-CM-HSANPs, the pharmacokinetic parameters of CM were not significantly different from those of CM-loaded human serum albumin NPs. The improved antitumor activity of F-CM-HSANPs may be attributable to the protection of drug from enzymatic deactivation followed by the selective localization at the desired site. These results suggest that the intravenous injection of F-CM-HSANPs is likely to have an advantage in the current clinical CM formulation, because it does not require the use of a solubilization agent and it is better able to target the tumor tissue.

Lentivirus-mediated knockdown of rhomboid domain containing 1 inhibits colorectal cancer cell growth.

Rhomboid domain containing 1 (RHBDD1), is a member of the rhomboid protease family, which has a pivotal role in the progression of numerous severe malignancies. However, its role in colorectal carcinoma (CRC) remains to be elucidated. In the present study, RHBDD1 was shown to be widely expressed in CRC cell lines. Lentivirus-mediated RNA interference was employed to knockdown RHBDD1 expression in RKO CRC cells. Functional analyses indicated that depletion of RHBDD1 expression resulted in significantly reduced CRC cell proliferation and colony formation, and induced a G0/G1 phase cell cycle arrest. The findings of the present study suggest that RHBDD1 may contribute to CRC tumorigenesis and serve as a potential therapeutic target in human CRC.

Reaction analysis and visualization of ReaxFF molecular dynamics simulations.

ReaxFF MD (Reactive Force Field Molecular Dynamics) is a promising method for investigating complex chemical reactions in relatively larger scale molecular systems. The existing analysis tools for ReaxFF MD lack the capability of capturing chemical reactions directly by analyzing the simulation trajectory, which is critical in exploring reaction mechanisms. This paper presents the algorithms, implementation strategies, features, and applications of VARxMD, a tool for Visualization and Analysis of Reactive Molecular Dynamics. VARxMD is dedicated to detailed chemical reaction analysis and visualization from the trajectories obtained in ReaxFF MD simulations. The interrelationships among the atoms, bonds, fragments, species and reactions are analyzed directly from the three-dimensional (3D) coordinates and bond orders of the atoms in a trajectory, which are accomplished by determination of atomic connectivity for recognizing connected molecular fragments, perception of bond types in the connected fragments for molecules or radicals, indexing of all these molecules or radicals (chemical species) based on their 3D coordinates and recognition of bond breaking or forming in the chemical species for reactions. Consequently, detailed chemical reactions taking place between two sampled frames can be generated automatically. VARxMD is the first tool specialized for reaction analysis and visualization in ReaxFF MD simulations. Applications of VARxMD in ReaxFF MD simulations of coal and HDPE (high-density polyethylene) pyrolysis show that VARxMD provides the capabilities in exploring the reaction mechanism in large systems with complex chemical reactions involved that are difficult to access manually.