Overall Survival Benefit in Rectal Cancer After Neoadjuvant Radiotherapy and Adjuvant Chemotherapy: A Propensity-Matched Population-Based Study.

BACKGROUND: It is well known that neoadjuvant radiotherapy could reduce local recurrence followed by surgical resection. However, evidence about oncologic efficacy of radiotherapy and survival benefit of adjuvant chemotherapy after neoadjuvant radiotherapy is still lacking. METHODS: This retrospective propensity score-matched cohort study identified patients with pathologically confirmed rectal cancer and receiving surgery with curative intent from the Surveillance, Epidemiology, and End Results database from 2004 through 2014. Overall survival was compared using the stratified log-rank test. Multivariate Cox regression analysis was used for identifying risk factor and developing prediction nomogram. RESULTS: A total of 22,008 (11,004 for each group) propensity-matched patients were identified. In the context of receiving adjuvant chemotherapy after surgical resection, there was no significant difference in terms of overall survival between surgery alone group and neoadjuvant radiotherapy and surgery group, whether for stage I (log-rank test p = 0.467), stage II (log-rank test p = 0.310), or stage III (p = 0.994). In case of receiving a prior combination therapy of neoadjuvant radiotherapy and surgery, the following adjuvant chemotherapy could significantly improve overall survival for patients with stage I (log-rank test p <0.001), stage II (log-rank test p = 0.038), and stage III (log-rank test p = 0.014). Nomogram integrating clinicopathologic factors was developed to predict survival benefit associated with neoadjuvant radiotherapy. Calibration and ROC curves validated promising performance for the nomogram. CONCLUSION: Patients with rectal cancer underwent neoadjuvant radiotherapy yield acceptable outcomes and are more likely to benefit from adjuvant chemotherapy in terms of overall survival. These data would be evidential for advocating consistency in guideline adherence to the use of adjuvant chemotherapy after neoadjuvant radiotherapy.

Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer (GC) has not been fully elucidated. AIM: To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC. METHODS: Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pcHOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXD-AS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis. RESULTS: The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway. CONCLUSION: These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.

Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1.

Cantharidin (CTD) is a traditional Chinese medicine that shows an anticancer effects in multiple types of cancer cells. However, the mechanism of CTD anti-cancer function in gastric cancer (GC) is still unclear. The aim of the present study was to investigate the underlying mechanism that CTD inhibits proliferation and migration through suppression of the PI3K/Akt signaling. CTD induced GC cell apoptosis and inhibited metastasis measured by CCK8 assays as well as wound healing assays and transwell assays. Mechanistic investigations suggested that CTD modulated the PI3K/Akt signaling via western-blot and quantitative q-PCR. In addition, we identified and confirmed CCAT1 as a novel direct target of CTD inhibited PI3K/AKt signaling expression. In conclusion, our results provide new point into the critical role of CTD in suppressing PI3K/Akt signaling via down-regulation of CCAT1, resulting in suppression GC cell growth and migration/invasion.

The long non-coding RNA LINC01606 contributes to the metastasis and invasion of human gastric cancer and is associated with Wnt/ß-catenin signaling.

The dysregulation of long non-coding RNA (lncRNA) has increasingly been linked to human gastric cancer (GC). However, the LINC01606 expression level and clinical values, and its role in the molecular mechanism underlying GC remain largely unknown. In our research, we found that LINC010606 was elevated aberrantly and correlated with metastasis and invasion in GC patients. Moreover, we found that LINC01606 expression level was associated with Wnt/ß-catenin signaling. In addition, subsequent functional experiments showed that JW74, a specific Wnt/ß-catenin signaling inhibitor, inhibited the transcription of LINC01606 and suppressed migration and invasion in GC cell lines. We also revealed that LINC01606 might be associated with miR-423-5p to regulate the level to which the Wnt/ß-catenin signaling pathway is activated. In summary, the findings of this study, based on competing endogenous RNA (ceRNA) theory, combine new data on the interaction between miR-423-5p and Wnt3a and introduce LINC01606 as a new focus for research, thus providing new insight into possible molecular-level approaches to preventing the migration and invasion of GC.

Primary mesenteric adenocarcinoma covered by abscess of the mesocolon and intestinal obstruction: A case report.

Primary mesenteric adenocarcinoma (PMA) is a rare malignant disease. A case of PMA that was covered by an abscess of the mesocolon and intestinal obstruction is reported in the present study. As the onset site of PMA is often obscured or hidden, there may be no clinical symptoms in the early stage. At the advanced stage, the tumor size is large enough to induce intestinal obstruction, perforation, bleeding, volvulus and other clinical symptoms in the majority of patients. Computed tomography scans, ultrasound and other auxiliary examinations are not sufficiently accurate for diagnosing PMA with non-specific characteristics in the majority of cases, causing certain difficulties in the pre-operative diagnosis of PMA, which easily lead to misdiagnosis. The main effective treatment of PMA is surgical resection as early as possible. Thus, when a patient is suspected of having malignancies, and gastrointestinal cancer and other malignancies of the digestive organs may be excluded, the possibility of PMA should be considered.

Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor prognosis and promotes tumor growth in gastric cancer.

Many lncRNA and mRNA sense-antisense transcripts have been systematically identified in malignant cells. However, the molecular mechanisms of most lncRNA-mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer-associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is significantly down-regulated in gastric cancer and could promote tumor growth in vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11 via the ASK1-p38MAPK/JNK signaling pathway. These findings suggest that decreased expression of SLC7A11-AS1 contributes to the progression of gastric cancer and may be a novel diagnostic biomarker and effective therapeutic target in gastric cancer patients.

Safety and efficacy of intraoperative iodine-125 seed implantation brachytherapy for rectal cancer patients: A retrospective clinical research.

BACKGROUND: This pilot study was performed to evaluate the risk of anastomotic leakage (AL) and pelvic autonomic nerve dysfunction, and the effects of (125) I brachytherapy after intraoperative permanent implantation of iodine-125 seeds within the patients with rectal carcinoma. METHODS: In a cohort consisting of 80 rectal cancer patients who received potentially curative resection of rectal carcinoma with implantation of (125) I brachytherapy or radical resection of rectal carcinoma underwent total mesorectal excision. The incidences of AL, fecal incontinence, urinary dysfunction, and sexual dysfunction were calculated for comparison, and risk factors for these complications were analyzed by logistic regression. Rates of tumor recurrence and overall survival were evaluated. RESULTS: Six out of 17 (35.29%) patients in the (125) I implant group and 1 out of 34 (2.94%) patients in the non-implant group were complicated with AL (P = 0.006). The incidences of urinary dysfunction (P = 0.005) and fecal incontinence (P = 0.023) were significantly different between the two groups. Multivariate analyses revealed that (125) I brachytherapy was an independent risk factor for AL (odds ratio, 18.702; 95%CI, 1.802-194.062; P = 0.014) and urinary dysfunction (odds ratio, 4.340; 95%CI, 1.158-16.264; P = 0.029), respectively. At postoperative 2-year, the recurrence rates were 5.56% in the (125) I implant group and 9.09% in the non-implant group (P = 0.029). CONCLUSIONS: Intraoperative implantation of (125) I brachytherapy significantly increases the risk of AL, fecal incontinence, urinary dysfunction, and improves local control and do not improve overall survival after total mesorectal excision.

Clinical comparison of antrum-preserving double tract reconstruction vs roux-en-Y reconstruction after gastrectomy for Siewert types II and III adenocarcinoma of the esophagogastric junction.

AIM: To explore a reasonable method of digestive tract reconstruction, namely, antrum-preserving double-tract reconstruction (ADTR), for patients with adenocarcinoma of the esophagogastric junction (AEG) and to assess its efficacy and safety in terms of long-term survival, complications, morbidity and mortality. METHODS: A total of 55 cases were retrospectively collected, including 18 cases undergoing ADTR and 37 cases of Roux-en-Y reconstruction (RY) for AEG (Siewert types II and III) at North Sichuan Medical College. The cases were divided into two groups. The clinicopathological characteristics, perioperative outcomes, postoperative complications, morbidity and overall survival (OS) were compared for the two different reconstruction methods. RESULTS: Basic characteristics including sex, age, body mass index (BMI), Siewert type, pT status, pN stage, and lymph node metastasis were similar in the two groups. No significant differences were found between the two groups in terms of perioperative outcomes (including the length of postoperative hospital stay, operating time, and intraoperative blood loss) and postoperative complications (consisting of anastomosis-related complications, wound infection, respiratory infection, pleural effusion, lymphorrhagia, and cholelithiasis). For the ADTR group, perioperative recovery indexes such as time to first flatus (P = 0.002) and time to resuming a liquid diet (P = 0.001) were faster than those for the RY group. Moreover, the incidence of reflux esophagitis was significantly decreased compared with the RY group (P = 0.048). The postoperative morbidity and mortality rates for overall postoperative complications and the rates of tumor recurrence and metastasis were not significantly different between the two groups. Survival curves plotted using the Kaplan-Meier method and compared by log-rank test demonstrated similar outcomes for the ADTR and RY groups. Multivariate analysis of significantly different factors that presented as covariates on Cox regression analysis to assess the survival and recurrence among AEG patients showed that age, gender, BMI, pleural effusion, time to resuming a liquid diet, lymphorrhagia and tumor-node-metastasis stage were important prognostic factors for OS of AEG patients, whereas the selection of surgical method between ADTR and RY was shown to be a similar prognostic factor for OS of AEG patients. CONCLUSION: ADTR by jejunal interposition presents similar rates of tumor recurrence, metastasis and long-term survival compared with classical reconstruction with RY esophagojejunostomy; however, it offers considerably improved near-term quality of life, especially in terms of early recovery and decreased reflux esophagitis. Thus, ADTR is recommended as a worthwhile digestive tract reconstruction method for Siewert types II and III AEG.

The Medicinal Values of Culinary-Medicinal Royal Sun Mushroom (Agaricus blazei Murrill).

Agaricus blazei Murrill (ABM), a mushroom native to Brazil, is a basidiomycete brown fungus, which is popularly known as "Cogumelo do Sol" in Brazil or "Himematsutake" in Japan, and there has been a prominent increase in the use of ABM for therapeutic and medicinal purposes. ABM is useful against a variety of diseases like cancer, tumor, chronic hepatitis, diabetes, atherosclerosis, hypercholesterolemia, and so on. In this review, we demonstrated various pharmacological effects of ABM, so that we can use different effects of ABM against different diseases and provide reference for the study of ABM in the future.

The BUD2 mutation affects plant architecture through altering cytokinin and auxin responses in Arabidopsis.

The ratio of auxin and cytokinin plays a crucial role in regulating aerial architecture by promoting or repressing axillary bud outgrowth. We have previously identified an Arabidopsis mutant bud2 that displays altered root and shoot architecture, which results from the loss-of-function of S-adenosylmethionine decarboxylase 4 (SAMDC4). In this study, we demonstrate that BUD2 could be induced by auxin, and the induction is dependent on auxin signaling. The mutation of BUD2 results in hyposensitivity to auxin and hypersensitivity to cytokinin, which is confirmed by callus induction assays. Our study suggests that polyamines may play their roles in regulating the plant architecture through affecting the homeostasis of cytokinins and sensitivities to auxin and cytokinin.

DWARF27, an iron-containing protein required for the biosynthesis of strigolactones, regulates rice tiller bud outgrowth.

Tillering in rice (Oryza sativa) is one of the most important agronomic traits that determine grain yields. Previous studies on rice tillering mutants have shown that the outgrowth of tiller buds in rice is regulated by a carotenoid-derived MAX/RMS/D (more axillary branching) pathway, which may be conserved in higher plants. Strigolactones, a group of terpenoid lactones, have been recently identified as products of the MAX/RMS/D pathway that inhibits axillary bud outgrowth. We report here the molecular genetic characterization of d27, a classic rice mutant exhibiting increased tillers and reduced plant height. D27 encodes a novel iron-containing protein that localizes in chloroplasts and is expressed mainly in vascular cells of shoots and roots. The phenotype of d27 is correlated with enhanced polar auxin transport. The phenotypes of the d27 d10 double mutant are similar to those of d10, a mutant defective in the ortholog of MAX4/RMS1 in rice. In addition, 2'-epi-5-deoxystrigol, an identified strigolactone in root exudates of rice seedlings, was undetectable in d27, and the phenotypes of d27 could be rescued by supplementation with GR24, a synthetic strigolactone analog. Our results demonstrate that D27 is involved in the MAX/RMS/D pathway, in which D27 acts as a new member participating in the biosynthesis of strigolactones.

Short panicle1 encodes a putative PTR family transporter and determines rice panicle size.

The architecture of the rice inflorescence, which is determined mainly by the number and length of primary and secondary inflorescence branches, is of importance in both agronomy and developmental biology. The position and number of primary branches are established during the phase transition from vegetative to reproductive growth, and several of the genes identified as participating in this process do so by regulating the meristemic activities of inflorescence. However, little is known about the molecular mechanism that controls inflorescence branch elongation. Here, we report on a novel rice mutant, short panicle1 (sp1), which is defective in rice panicle elongation, and thus leads to the short-panicle phenotype. Gene cloning and characterization indicate that SP1 encodes a putative transporter that belongs to the peptide transporter (PTR) family. This conclusion is based on the findings that SP1 contains a conserved PTR2 domain consisting of 12 transmembrane domains, and that the SP1-GFP fusion protein is localized in the plasma membrane. The SP1 gene is highly expressed in the phloem of the branches of young panicles, which is consistent with the predicted function of SP1 and the sp1 phenotype. Phylogenetic analysis implies that SP1 might be a nitrate transporter. However, neither nitrate transporter activity nor any other compounds transported by known PTR proteins could be detected in either a Xenopus oocyte or yeast system, in our study, suggesting that SP1 may need other component(s) to be able to function as a transporter, or that it transports unknown substrates in the monocotyledonous rice plant.

LAZY1 controls rice shoot gravitropism through regulating polar auxin transport.

Tiller angle of rice (Oryza sativa L.) is an important agronomic trait that contributes to grain production, and has long attracted attentions of breeders for achieving ideal plant architecture to improve grain yield. Although enormous efforts have been made over the past decades to study mutants with extremely spreading or compact tillers, the molecular mechanism underlying the control of tiller angle of cereal crops remains unknown. Here we report the cloning of the LAZY1 (LA1) gene that regulates shoot gravitropism by which the rice tiller angle is controlled. We show that LA1, a novel grass-specific gene, is temporally and spatially expressed, and plays a negative role in polar auxin transport (PAT). Loss-of-function of LA1 enhances PAT greatly and thus alters the endogenous IAA distribution in shoots, leading to the reduced gravitropism, and therefore the tiller-spreading phenotype of rice plants.

BUD2, encoding an S-adenosylmethionine decarboxylase, is required for Arabidopsis growth and development.

Polyamines are implicated in regulating various developmental processes in plants, but their exact roles and how they govern these processes still remain elusive. We report here an Arabidopsis bushy and dwarf mutant, bud2, which results from the complete deletion of one member of the small gene family that encodes S-adenosylmethionine decarboxylases (SAMDCs) necessary for the formation of the indispensable intermediate in the polyamine biosynthetic pathway. The bud2 plant has enlarged vascular systems in inflorescences, roots, and petioles, and an altered homeostasis of polyamines. The double mutant of bud2 and samdc1, a knockdown mutant of another SAMDC member, is embryo lethal, demonstrating that SAMDCs are essential for plant embryogenesis. Our results suggest that polyamines are required for the normal growth and development of higher plants.

BRITTLE CULM1, which encodes a COBRA-like protein, affects the mechanical properties of rice plants.

Plant mechanical strength is an important agronomic trait. To understand the molecular mechanism that controls the plant mechanical strength of crops, we characterized the classic rice mutant brittle culm1 (bc1) and isolated BC1 using a map-based cloning approach. BC1, which encodes a COBRA-like protein, is expressed mainly in developing sclerenchyma cells and in vascular bundles of rice. In these types of cells, mutations in BC1 cause not only a reduction in cell wall thickness and cellulose content but also an increase in lignin level, suggesting that BC1, a gene that controls the mechanical strength of monocots, plays an important role in the biosynthesis of the cell walls of mechanical tissues.

Control of tillering in rice.

Tillering in rice (Oryza sativa L.) is an important agronomic trait for grain production, and also a model system for the study of branching in monocotyledonous plants. Rice tiller is a specialized grain-bearing branch that is formed on the unelongated basal internode and grows independently of the mother stem (culm) by means of its own adventitious roots. Rice tillering occurs in a two-stage process: the formation of an axillary bud at each leaf axil and its subsequent outgrowth. Although the morphology and histology and some mutants of rice tillering have been well described, the molecular mechanism of rice tillering remains to be elucidated. Here we report the isolation and characterization of MONOCULM 1 (MOC1), a gene that is important in the control of rice tillering. The moc1 mutant plants have only a main culm without any tillers owing to a defect in the formation of tiller buds. MOC1 encodes a putative GRAS family nuclear protein that is expressed mainly in the axillary buds and functions to initiate axillary buds and to promote their outgrowth.

Silencing of phosphoethanolamine N-methyltransferase results in temperature-sensitive male sterility and salt hypersensitivity in Arabidopsis.

S-Adenosyl-L-methionine:phosphoethanolamine N-methyltransferase (PEAMT; EC 2.1.1.103) catalyzes the key step in choline (Cho) biosynthesis, the N-methylation of phosphoethanolamine. Cho is a vital precursor of the membrane phospholipid phosphatidylcholine, which accounts for 40 to 60% of lipids in nonplastid plant membranes. Certain plants use Cho to produce the osmoprotectant glycine betaine, which confers resistance to salinity, drought, and other stresses. An Arabidopsis mutant, t365, in which the PEAMT gene is silenced, was identified using a new sense/antisense RNA expression system. t365 mutant plants displayed multiple morphological phenotypes, including pale-green leaves, early senescence, and temperature-sensitive male sterility. Moreover, t365 mutant plants produced much less Cho and were hypersensitive to salinity. These results demonstrate that Cho biosynthesis not only plays an important role in plant growth and development but also contributes to tolerance to environmental stresses. The temperature-sensitive male sterility caused by PEAMT silencing may have a potential application in agriculture for engineering temperature-sensitive male sterility in important crop plants.