Tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: influencing factors and prognostic significance.

OBJECTIVE: The extent of tumor regression varies widely among patients who receive neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision (TME) surgery. We evaluated the tumor regression grade (TRG) classification of patients and analyzed factors related to TRG and its value in predicting prognosis in locally advanced rectal cancer (LARC). METHODS: This study retrospectively analyzed the clinicopathologic data of 269 consecutive patients with LARC treated from February 2002 to October 2014. The grade of TRG was based on the extent of primary tumor replaced by fibrosis. Clinical characteristics and relative survival were retrospectively analyzed. RESULTS: There were 269 patients, among whom 67 patients (24.9%) achieved TRG0, whereas 46 patients (17.1%) showed TRG3. TRG1 and TRG2 were both found in 78 patients (29.0%). Clinicopathologic factors that were related to TRG included post-NACRT carcinoembryonic antigen (CEA) level (P=0.002), clinical T stage (P=0.022), pathologic T stage (P<0.001) and pathologic lymph node status (P=0.003). The 5-year overall survival (OS) was 74.6%, 55.1%, 47.4%, 28.3% for TRG0, TRG1, TRG2, TRG3, respectively (P<0.001). The 5-year disease-free survival (DFS) was 64.2%, 47.4%, 37.2%, 23.9% for TRG0, TRG1, TRG2, TRG3, respectively (P<0.001). Based on multivariate analysis, TRG was a significant predictor for both OS (P=0.039) and DFS (P=0.043). CONCLUSION: Clinicopathologic factors such as post-NACRT CEA level, clinical T stage, pathological T stage and pathological lymph node status are significantly associated with TRG. TRG is an independent predictor of survival. Therefore, it is reasonable to include the TRG for clinicopathologic assessment.

Sixteen Novel Mycoviruses Containing Positive Single-Stranded RNA, Double-Stranded RNA, and Negative Single-Stranded RNA Genomes Co-Infect a Single Strain of Rhizoctonia zeae.

In the present study, sixteen novel RNA mycoviruses co-infecting a single strain of Rhizoctonia zeae (strain D40) were identified and molecularly characterized using metatranscriptome sequencing combined with a method for rapid amplification of cDNA ends. The fungal strain was isolated from diseased seedlings of sugar beet with damping-off symptoms. Based on genome analysis and phylogenetic analysis of amino acid sequences of RNA-dependent RNA polymerase, the sixteen mycoviruses associated with strain D40 contained three genome types with nine distinct lineages, including positive single-stranded RNA (Hypoviridae, Yadokariviridae, Botourmiaviridae, and Gammaflexiviridae), double-stranded RNA (Phlegiviridae, Megabirnaviridae, Megatotiviridae, and Yadonushiviridae), and negative single-stranded RNA (Tulasviridae), suggesting a complex composition of a mycoviral community in this single strain of R. zeae (strain D40). Full genome sequences of six novel mycoviruses and the nearly full-length sequences of the remaining ten novel mycoviruses were obtained. Furthermore, seven of these sixteen mycoviruses were confirmed to assemble virus particles present in the R. zeae strain D40. To the best of our knowledge, this is the first detailed study of mycoviruses infecting R. zeae.

Patterns of Lymph Node Metastasis and Optimal Surgical Strategy in Small (≤20 mm) Gastroenteropancreatic Neuroendocrine Tumors.

Background: Regional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination. Methods: This retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest. Results: Of 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33-0.66; p < 0.001; 11-20 mm: HR, 0.54; 95% CI, 0.34-0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02-0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16-0.96; p = 0.041) and c-NETs of 11-20 mm (HR, 0.07; 95% CI, 0.01-0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size. Conclusions: Given the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11-20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.

Knowledge Domain and Hotspots Predict Concerning Electroactive Biomaterials Applied in Tissue Engineering: A Bibliometric and Visualized Analysis From 2011 to 2021.

Objective: Electroactive biomaterials used in tissue engineering have been extensively studied. Electroactive biomaterials have unique potential advantages in cell culture and tissue regeneration, which have attracted the attention of medical researchers worldwide. Therefore, it is important to understand the global scientific output regarding this topic. An analysis of publications on electroactive biomaterials used in tissue engineering over the past decade was performed, and the results were summarised to track the current hotspots and highlight future directions. Methods: Globally relevant publications on electroactive biomaterials used in tissue engineering between 2011 and 2021 were extracted from the Web of Science database. The VOSviewer software and CiteSpace were employed to visualise and predict trends in research on the topic. Results: A total of 3,374 publications were screened. China contributed the largest number of publications (995) and citations (1581.95, actual value ×0.05). The United States achieved the highest H-index (440 actual values ×0.05). The journal Materials Science & Engineering C-materials for Biological Applications (IF = 7.328) published the most studies on this topic (150). The Chinese Academy of Science had the largest number of publications (107) among all institutions. The publication titled Nanotechnological strategies for engineering complex tissues by Dir, T of the United States had the highest citation frequency (985 times). Regarding the function of electroactive materials, the keyword "sensors" emerged in recent years. Regarding the characterisation of electroactive materials, the keyword "water contact angle" appeared lately. Regarding electroactive materials in nerve and cardiac tissue engineering, the keywords "silk fibroin and conductive hydrogel" appeared recently. Regarding the application of electroactive materials in bone tissue engineering, the keyword "angiogenesis" emerged in recent years. The current research trend indicates that although new functional materials are constantly being developed, attention should also be paid to their application and transformation in tissue engineering. Conclusion: The number of publications on electroactive biomaterials used in tissue engineering is expected to increase in the future. Topics like sensors, water contact angle, angiogenesis, silk fibroin, and conductive hydrogels are expected to be the focuses of research in the future; attention should also be paid to the application and transformation of electroactive materials, particularly bone tissue engineering. Moreover, further development of the field requires joint efforts from all disciplines.

Phase II study of anlotinib in combination with oxaliplatin and capecitabine for patients with RAS/BRAF wild-type metastatic colorectal adenocarcinoma as the first-line therapy.

BACKGROUND: Anlotinib, an oral small molecule tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR a/ß, and c-kit, had demonstrated prolonged progression-free survival (PFS) in refractory metastatic colorectal cancer (mCRC). This multicenter, single-arm, phase II, exploratory study was conducted to evaluate the efficacy and safety of anlotinib combined with capecitabine and oxaliplatin as first-line treatment for unresectable RAS/BRAF wild-type mCRC. METHODS: Patients aged 18-75 with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment, and ECOG performance status ≤1 were enrolled. Eligible patients received capecitabine (850 mg/m2, p.o., bid, on day 1-14 every 21 days), oxaliplatin (130 mg/m2, i.v., on day 1 every 21 days), and anlotinib (12 mg, p.o., qd, on days 1-14 every 21 days) as induction therapy. Following 6 cycles of therapy, patients who achieved response or stable disease received capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint was objective response rate (ORR) according to RECIST (version: 1.1), and the secondary endpoints were PFS, disease control rate (DCR), duration of response (DOR), and safety. RESULTS: Between November 2019 and February 2021, 31 patients were enrolled. One patient was excluded for refusing treatment. The primary endpoint of ORR was 76.7% (95% CI, 57.7-90.1) with 1 patient achieving a complete response and 22 patients partial response. DCR was 93.3% (95% CI, 77.9-99.2). At a median follow-up of 14.1 months (95% CI, 9.9-18.3), median PFS was 11.3 months (95% CI, 7.1-14.1), and DOR was 7.9 months (95% CI, 5.5-12.7). Twenty-five (83.3%) patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). No grade 5 TEAE was reported. The most common grade 3 or 4 TEAEs (>10%) were hypertension (15/30; 50%), neutrophil count decreased (8/30; 26.7%), and diarrhea (4/30; 13.3%). A total of 18 (60%) patients had TEAEs that resulted in dose reduction, interruptions, or delays. CONCLUSIONS: Anlotinib combined with capecitabine and oxaliplatin showed considerable ORR, DCR, PFS, and DOR in the first-line therapy of mCRC with manageable toxicity profiles. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04080843.

The relationship between amino acid and lipid metabolism in oleaginous eukaryotic microorganism.

Amino acids are the building blocks of protein, promoting the balance between growth and lipid synthesis. However, the accumulation of microbial lipids involves multiple pathways, which requires the analysis of the global cellular metabolic network in which amino acid metabolism is involved. This review illustrates the dependence patterns of intracellular amino acids and lipids of oleaginous eukaryotic microorganisms in different environments and points out the contribution of amino acid metabolic precursors to the de novo synthesis of fatty acids. We emphasized the key role of amino acid metabolism in lipid remodeling and autophagy behavior and highlighted the regulatory effects of amino acids and their secondary metabolites as signal factors for microbial lipid synthesis. The application prospects of omics technology and genetic engineering technology in the field of microbial lipids are described. KEY POINTS: • Overview of microbial lipid synthesis mediated by amino acid metabolism • Insight into metabolic mechanisms founding multiple regulatory networks is provided • Description of microbial lipid homeostasis mediated by amino acid excitation signal.

Efficacy and safety of PD-1 inhibitor combined with antiangiogenic therapy for unresectable hepatocellular carcinoma: A multicenter retrospective study.

BACKGROUND: Immunotherapy-antiangiogenesis combination therapy has achieved excellent survival outcomes in hepatocellular carcinoma (HCC) in clinical trials. However, the combination therapy for HCC outside clinical trials is not well studied, and predictive factors are lacking. Here, we retrospectively analyzed the efficacy and safety of immunotherapy-antiangiogenesis combination therapy in unresectable HCC patients in a real-world setting. METHODS: We conducted a four-center, retrospective study of unresectable HCC patients who received the combination of programmed death 1 (PD-1) inhibitor and antiangiogenic agent between April 2018 and July 2021 in China. RESULTS: In total, 136 patients were enrolled in the cohort. The objective response rate (ORR) and disease control rate (DCR) were 38.0% and 81.8%, respectively. The median time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were 7.2, 7.3, and 19.6 months, respectively. The multivariate analysis indicated that ECOG performance status score (PS) 2 was a significantly independent negative factor of ORR. Moreover, ECOG PS 2, peritoneum metastasis and previous immunotherapy were found to be independent negative predictors of PFS. A shorter OS was associated with ECOG PS 2, peritoneum metastasis, the presence of previous immunotherapy, Child-Pugh stage B, and high alpha-fetoprotein (AFP) concentration. One hundred and twenty-five patients (91.9%) reported adverse events (AEs) with any grade. CONCLUSION: We elucidated the efficacy and safety of immunotherapy-antiangiogenesis combination therapy and identified potential predictors for response and survival in a real-world cohort of patients with unresectable HCC.

Pulmonary lesion subtypes recognition of COVID-19 from radiomics data with three-dimensional texture characterization in computed tomography images.

BACKGROUND: The COVID-19 disease is putting unprecedented pressure on the global healthcare system. The CT (computed tomography) examination as a auxiliary confirmed diagnostic method can help clinicians quickly detect lesions locations of COVID-19 once screening by PCR test. Furthermore, the lesion subtypes classification plays a critical role in the consequent treatment decision. Identifying the subtypes of lesions accurately can help doctors discover changes in lesions in time and better assess the severity of COVID-19. METHOD: The most four typical lesion subtypes of COVID-19 are discussed in this paper, which are GGO (ground-glass opacity), cord, solid and subsolid. A computer-aided diagnosis approach of lesion subtype is proposed in this paper. The radiomics data of lesions are segmented from COVID-19 patients CT images with diagnosis and lesions annotations by radiologists. Then the three-dimensional texture descriptors are applied on the volume data of lesions as well as shape and first-order features. The massive feature data are selected by HAFS (hybrid adaptive feature selection) algorithm and a classification model is trained at the same time. The classifier is used to predict lesion subtypes as side decision information for radiologists. RESULTS: There are 3734 lesions extracted from the dataset with 319 patients collection and then 189 radiomics features are obtained finally. The random forest classifier is trained with data augmentation that the number of different subtypes of lesions is imbalanced in initial dataset. The experimental results show that the accuracy of the four subtypes of lesions is (93.06%, 96.84%, 99.58%, and 94.30%), the recall is (95.52%, 91.58%, 95.80% and 80.75%) and the f-score is (93.84%, 92.37%, 95.47%, and 84.42%). CONCLUSION: The three-dimensional radiomics features used in this paper can better express the high-level information of COVID-19 lesions in CT slices. HAFS method aggregates the results of multiple feature selection algorithms intersects with traditional methods to filter out redundant features more accurately. After selection, the subtype of COVID-19 lesion can be judged by inputting the features into the RF (random forest) model, which can help clinicians more accurately identify the subtypes of COVID-19 lesions and provide help for further research.

Thrombin immobilized polydopamine-diatom biosilica for effective hemorrhage control.

In this study, an efficient composite hemostatic material (DA-diatom-T) was prepared, using a polydopamine layer as a linker to immobilize thrombin on the surface of diatom biosilica. DA-diatom-T retained the porous structure of the diatom with high water absorption capacity, which can absorb 31 times its own weight of water. The thrombin activity of DA-diatom-T was as high as 5.81 U mg-1 that could be maintained at 67% after 30 days at room temperature. DA-diatom-T exhibited non-toxicity to mouse fibroblast cell lines, favorable hemocompatibility and fast procoagulant ability. DA-diatom-T could promote the initiation of the coagulation process and increase platelet activity and blood clot strength to form a physical barrier at the wound. In an in vivo study, DA-diatom-T could significantly reduce the clotting time and reduce the bleeding volume. The above results showed that DA-diatom-T had potential as a new hemostatic material.

The re-evaluation of optimal lymph node yield in stage II right-sided colon cancer: is a minimum of 12 lymph nodes adequate?

PURPOSE: Adequate lymphadenectomy is critical for accurate nodal staging and planning adjuvant therapy in colon cancer. However, the optimal lymph node (LN) yield for stage II right-sided colon cancer (RSCC) is still unclear. This population-based study aimed to determine the optimal LN yield associated with survival and LN positivity in patients with stage II RSCC. METHODS: All patients with stage II-III RSCC were identified from the Surveillance, Epidemiology, and End Results database over a 10-year interval (2006-2015). The optimal threshold for LN yield was explored using an outcome-oriented approach based on survival and LN positivity. RESULTS: The median number of LNs examined for all 17,385 patients with stage II RSCC was 17 (IQR 12-23). Nineteen LNs were determined as the optimal cut-off point to maximize survival benefit from lymphadenectomy. Increased LN yield was associated with a gradual increase in the risk of node positivity, with no change after 19 nodes. Compared with patients with 19 or more LNs examined, the group with fewer LNs had a significantly poor cancer-specific survival (< 12 nodes: hazard ratio (HR) 2.26, P < 0.001; 12-18 nodes: HR 1.58, P < 0.001) and overall survival (< 12 nodes: HR 1.80, P < 0.001; 12-18 nodes: HR 1.31, P < 0.001). Similar survival results were found in the validation cohort. Patients with older age, small tumor size, and appendix and transverse colon cancer were more likely to receive inadequate LN harvest. CONCLUSION: A minimum of 19 LNs is needed to be examined for optimal survival and adequate node staging in lymph node-negative RSCC.

Histological tumor response assessment in colorectal liver metastases after neoadjuvant chemotherapy: impact of the variation in tumor regression grading and peritumoral lymphocytic infiltration.

Background: The objective of this study was to evaluate the prognostic value of the variation in tumor regression grade (TRG) and peritumoral lymphocytic infiltration of colorectal liver metastases (CRLMs) after neoadjuvant chemotherapy (NACT). Methods: A retrospective review was performed in 98 patients with CRLMs who underwent NACT between 2010 and 2016. The TRG scores and counts of TILs at the tumor-normal interface were assessed in all 176 resected liver metastases to determine their association with prognosis. According to the variation in TRG scores, 40 patients with more than one liver metastasis were divided into a decreased TRG group and a stable TRG group. An additional independent cohort of 64 patients with 106 resected liver specimens was established to validate our main findings. Results: In the derivation cohort of 98 patients, 41.8% patients had a favourable pathological response to NACT (TRG 1-3), which were significantly associated with improved prognosis. Seventeen patients (42.5%) showed decreased TRG scores, and the remaining patients had stable scores. The multivariate analysis indicated that patients with decreased TRG scores had a better recurrence-free survival (RFS) compared with those with stable TRG scores (HR=0.42, P=0.034), and a similar trend was observed in the validation cohort (P=0.068). Dense TILs surrounding the metastases were present in 55.1% of the derivation cohort and associated with pathological response (P=0.008). Among patients with a pathological response to NACT, those with dense TILs had a superior RFS compared to those with weak TILs in both cohorts (derivation: HR=0.36, P=0.035; validation: HR=0.34, P=0.016). Conclusions: Variation in TRG scores and peritumoral lymphocytic infiltration may be proposed as secondary pathological parameters to evaluate the pathological response to NACT and predict the risk of recurrence after liver surgery.

Treatment modalities and relative survival in patients with brain metastasis from colorectal cancer.

Standard treatment options for brain metastases (BM) from colorectal cancer (CRC) are controversial. The purpose of this study was to evaluate the efficacy of multidisciplinary treatment modalities and provide optimal therapeutic strategies for selected patients with different clinical characteristics. All eligible patients diagnosed with BM from CRC during the past two decades (1997-2016) were identified in our center. Clinical characteristics, treatment modalities and relative survival were retrospectively analyzed. Median overall survival after the identification of BM was 6 months. The 1- and 2- year survival rates were 29.40% and 5.70%, respectively. On multivariate analysis, the number of BMs, Karnofsky performance score and the treatment modalities were found to be independent prognostic factors (the p-value was 0.006, 0.001 and < 0.001, respectively). In conclusion, multidisciplinary treatment is supported to be the optimal treatment for patients with BM from CRC. For patients with single brain metastases and KPS > 70, neurosurgery combined with chemotherapy could provide an additional survival benefit. For patients with multiple brain metastases or KPS ≤ 70, radiotherapy plus chemotherapy may be appropriate.

A modified TNM staging system for non-metastatic colorectal cancer based on nomogram analysis of SEER database.

BACKGROUND: To revise the American Joint Committee on Cancer TNM staging system for colorectal cancer (CRC) based on a nomogram analysis of Surveillance, Epidemiology, and End Results (SEER) database, and to prove the rationality of enhancing T stage's weighting in our previously proposed T-plus staging system. METHODS: Total 115,377 non-metastatic CRC patients from SEER were randomly grouped as training and testing set by ratio 1:1. The Nomo-staging system was established via three nomograms based on 1-year, 2-year and 3-year disease specific survival (DSS) Logistic regression analysis of the training set. The predictive value of Nomo-staging system for the testing set was evaluated by concordance index (c-index), likelihood ratio (L.R.) and Akaike information criteria (AIC) for 1-year, 2-year, 3-year overall survival (OS) and DSS. Kaplan-Meier survival curve was used to valuate discrimination and gradient monotonicity. And an external validation was performed on database from the Second Affiliated Hospital of Zhejiang University (SAHZU). RESULTS: Patients with T1-2 N1 and T1N2a were classified into stage II while T4 N0 patients were classified into stage III in Nomo-staging system. Kaplan-Meier survival curves of OS and DSS in testing set showed Nomo-staging system performed better in discrimination and gradient monotonicity, and the external validation in SAHZU database also showed distinctly better discrimination. The Nomo-staging system showed higher value in L.R. and c-index, and lower value in AIC when predicting OS and DSS in testing set. CONCLUSION: The Nomo-staging system showed better performance in prognosis prediction and the weight of lymph nodes status in prognosis prediction should be cautiously reconsidered.

ANGPTL1 attenuates colorectal cancer metastasis by up-regulating microRNA-138.

BACKGROUND: Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Nevertheless, its effects on colorectal cancer (CRC) remain poorly defined. In this study, we aim to demonstrate the biological function of ANGPTL1 in CRC cells. METHODS: We explored ANGPTL1 mRNA expression in human CRC tissues and its association with prognosis. CRC cell lines overexpressing ANGPTL1 or with ANGPTL1 knocked down were constructed and analyzed for changes in proliferation, colony formation, migration and invasion. ANGPTL1-regulated microRNAs were analyzed, and microRNA inhibitor and mimics were used to explore the role of microRNA in ANGPTL1-associated biological function. RESULTS: ANGPTL1 mRNA expression was down-regulated in CRC tissues, and high ANGPTL1 expression predicted better survival in CRC patients. ANGPTL1 overexpression resulted in suppressed migration and invasion in vitro, and it prolonged overall survival in mouse models. By contrast, its down-regulation enhanced migration and invasion of CRC cells. MicroRNA-138 expression was positively correlated with ANGPTL1 mRNA level in CRC tissues and up-regulated by ANGPTL1 in CRC cells. In addition, the microRNA-138 inhibitor or mimics could reverse or promote the ANGPTL1-mediated inhibition of the migratory capacity of CRC cells, respectively. CONCLUSIONS: This study is the first to demonstrate the biological function of ANGPTL1 in CRC cells. ANGPTL1 expression was down-regulated in CRC tissues and inversely correlated with poor survival. ANGPTL1 repressed migration and invasion of CRC cells, and microRNA-138 was involved in this process.

Cellular Phenotypic Analysis of Macrophage Activation Unveils Kinetic Responses of Agents Targeting Phosphorylation.

Macrophages are highly plastic cells, which serve as sentinels of the host immune system due to their ability to recognize and respond to microbial products rapidly and dynamically. Appropriate regulation of macrophage activation is essential for pathogen clearance or preventing autoimmune diseases. However, regularly used endpoint assays for analyzing macrophage functions have the limitations of being static and non-high throughput. In this study, we introduced a real-time and convenient method based on changes in cellular impedance that are detected by microelectronic biosensors. This new method can record the time/dose-dependent cell response profiles (TCRPs) of macrophages in real time and generates physiologically relevant data. The TCRPs generated from classically interferon-γ/lipopolysaccharide-activated macrophages showed considerable consistency with the data generated from standard endpoint assays. We further explored this approach by using it for global screening of a library of protein tyrosine kinase/phosphatase (PTK/PTP) inhibitors to investigate their impact on macrophage activation. Collectively, our findings suggest that the cellular impedance-based assay provides a promising approach for dynamically monitoring macrophage functions in a convenient and high-throughput manner.

The role of surgical intervention in primary colorectal lymphoma: A SEER population-based analysis.

BACKGROUND: Primary colorectal lymphoma (PCL) is a rare colorectal malignancy. The standard treatment and prognostic factors of PCL remain unexplored. Therefore, a large population-based study should be conducted to provide a detailed review of this disease. METHODS: We extracted the data of eligible patients with PCL registered in the SEER database from 1973 to 2011. All statistical analyses were performed using SPSS 19.0. RESULTS: A total of 2050 (61.3%) of the 3342 patients with PCL underwent surgical intervention, and 1292 (38.7%) patients received no surgical treatment. The median overall survival was 95 months, and patients receiving surgery exhibited significantly prolonged survival (adjusted HR =0.69, P <0.001). Young age, early tumor stage, and indolent lymphoma were independent predictors of improved survival. Further survival analyses demonstrated the potential benefit of surgery in patients with early tumor stage, right-sided lesions, or diffuse large B-cell PCL. Conversely, surgical intervention did not improve the survival of patients with advanced-stage, left-sided, or indolent PCL. CONCLUSION: PCL is a rare tumor that can be effectively treated. Surgical intervention may play an important role in the treatment of PCL. Early tumor stage, a right-sided lesion, and diffuse large B-cell histological PCL seem to be the clinical characteristics of optimal surgical candidates.

Incidence, Surgical Treatment, and Prognosis of Anorectal Melanoma From 1973 to 2011: A Population-Based SEER Analysis.

Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM.We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery.We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision.This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis.

Prognostic significance of matrix metalloproteinase 7 immunohistochemical expression in colorectal cancer: a meta-analysis.

Matrix metalloproteinase 7 (MMP-7) was speculated to have a key role in the development and progression of human cancer. Considerable studies investigated the relationship between its expression and survival in colorectal cancer (CRC), but inconsistent results were obtained. The clinical significance of MMP-7 overexpression in CRC remains controversial. Therefore, in this article, we conducted a meta-analysis to analyze the prognostic value of MMP-7 in CRC. We searched studies in PubMed, Medline, and Web of Science databases until August 2014 to find relevant studies. A total of six high-quality studies met the inclusion criteria and 1631 patients were included in our study. Combined hazard ratios (HRs) suggested that MMP-7 overexpression had an unfavorable impact on overall survival (HR = 1.83, 95% CI: 1.24-2.71). Subgroup and sensitivity analyses further validated the role of MMP-7 as a predictor for prognosis. In conclusion, MMP-7 overexpression detected by immunohistochemistry indicated worse prognosis in CRC and may help to guide clinical therapy.

Cypher/ZASP is a novel A-kinase anchoring protein.

PKA signaling is important for the post-translational modification of proteins, especially those in cardiomyocytes involved in cardiac excitation-contraction coupling. PKA activity is spatially and temporally regulated through compartmentalization by protein kinase A anchoring proteins. Cypher/ZASP, a member of PDZ-LIM domain protein family, is a cytoskeletal protein that forms multiprotein complexes at sarcomeric Z-lines. It has been demonstrated that Cypher/ZASP plays a pivotal structural role in the structural integrity of sarcomeres, and several of its mutations are associated with myopathies including dilated cardiomyopathy. Here we show that Cypher/ZASP, interacting specifically with the type II regulatory subunit RIIα of PKA, acted as a typical protein kinase A anchoring protein in cardiomyocytes. In addition, we show that Cypher/ZASP itself was phosphorylated at Ser(265) and Ser(296) by PKA. Furthermore, the PDZ domain of Cypher/ZASP interacted with the L-type calcium channel through its C-terminal PDZ binding motif. Expression of Cypher/ZASP facilitated PKA-mediated phosphorylation of the L-type calcium channel in vitro. Additionally, the phosphorylation of the L-type calcium channel at Ser(1928) induced by isoproterenol was impaired in neonatal Cypher/ZASP-null cardiomyocytes. Moreover, Cypher/ZASP interacted with the Ser/Thr phosphatase calcineurin, which is a phosphatase for the L-type calcium channel. Taken together, our data strongly suggest that Cypher/ZASP not only plays a structural role for the sarcomeric integrity, but is also an important sarcomeric signaling scaffold in regulating the phosphorylation of channels or contractile proteins.