Adjuvant Chemotherapy Seemed Not to Have Survival Benefit in Rectal Cancer Patients with ypTis-2N0 After Preoperative Radiotherapy and Surgery from a Population-Based Propensity Score Analysis.

BACKGROUND: Adjuvant chemotherapy is currently offered routinely, as standard, after radical resection for patients with rectal cancer receiving neo-adjuvant chemoradiation. However, the efficacy of adjuvant chemotherapy in patients with ypTis-2N0M0 has not been documented to the same extent, and the survival benefit remained controversial. The purpose of this work was to determine the role of chemotherapy in patients with ypTis-2N0M0 classification. MATERIALS AND METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results database (n = 4,217). A propensity score model was utilized to balance baseline covariates. RESULTS: Of the 4,217 included patients, 335 with ypTis-2N0M0 did not receive adjuvant chemotherapy. There were comparable cancer-specific survivals (CSS) between those undergoing adjuvant chemotherapy or not (log-rank test = 0.136, p = .712) in the overall sample. After propensity score matching, the cancer-specific survival did not differ between the chemotherapy and observation groups (log-rank test = 0.089, p = .765). Additionally, the Cox model did not demonstrate adjuvant chemotherapy as the prognostic factor, with hazard ratio = 0.95 (95% confidence interval 0.69-1.32) for CSS. Furthermore, the 10-year cumulative CSS was 78.7% and 79.4% between the chemotherapy and observation groups, indicating no significance, and no impact of adjuvant chemotherapy on survival was observed in different subgroups stratified by T stage, histological grade, histology, lymph nodes, and tumor size. CONCLUSION: Patients with ypTis-2N0 rectal cancer did not benefit from adjuvant chemotherapy after preoperative radiology and radical surgery in this cohort study. These results provided new insight into the routine use of adjuvant chemotherapy for patients with rectal cancer with completed neo-adjuvant radiotherapy and curative surgery. IMPLICATIONS FOR PRACTICE: Inconsistent recommendations for patients with rectal cancer receiving neo-adjuvant chemoradiation are offered by clinical guidelines. Adjuvant chemotherapy had no cancer-specific survival benefit, not only in the whole cohort, but also in the propensity score-matched cohort. A Cox model also confirmed adjuvant chemotherapy was not a significant prognostic factor in ypTis-2N0 rectal cancer. No survival benefit conferred by adjuvant chemotherapy was observed, regardless of whether T stage, histological type, grade, lymph nodes and tumor size varied.

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients.

BACKGROUND/AIMS: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. METHODS: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. RESULTS: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. CONCLUSION: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

Metastatic lymph node ratio can further stratify prognosis in rectal cancer patients treated with preoperative radiotherapy: a population-based analysis.

Recent studies have shown that it is not only the absolute number of involved lymph nodes (LNs) but also the ratio of metastatic lymph node that confers prognostic information. However, the impact of the lymph node ratio (LNR) on the prognosis of rectal cancer treated with preoperative radiotherapy is still not fully studied. In this study, Surveillance, Epidemiology, and End Results (SEER)-registered rectal cancer patients treated with preoperative radiotherapy (preop-RT) with LN metastasis were evaluated using multivariate Cox regression analysis to determine the prognostic role of the LNR. LNR optimal cutoff was identified by X-tile. The rationale of yielding pathological node stage (yp-N stage) and yielding pathological lymph node ratio stage (yp-rN stage) (LNR stage) was further combined for analysis. For the results, X-tile program determined 0.28 and 0.68 as optimal cutoff values in terms of survival in 1,872 rectal cancer patients treated with preoperative radiotherapy. yp-rN was significantly associated with 5-year rectal cancer cause-specific survival (RCSS) (P < 0.001). In a multivariate analysis, yp-rN was a significant independent prognostic factor for RCSS (hazard ratios, 1.277 and 1.631; P < 0.001). yp-rN had a prognostic impact on RCSS in patients with yp-N1 and yp-N2 subgroup. yp-N stage also had influenced on RCSS in all yp-rN stage. The yp-rN stage can be used together with the yp-N stage to select high-risk patients for postoperative treatment.

High expressions of galectin-1 and VEGF are associated with poor prognosis in gastric cancer patients.

High expressions of galectin-1 and vascular endothelial growth factor (VEGF) are correlated with biological behavior in some cancers. The aim of this study is to evaluate the expressions of galectin-1 and VEGF in gastric cancer and investigate their relationships with clinicopathological factors and prognostic significance. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on 108 cases of gastric cancer. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathological variables, and survival rates was analyzed. Immunohistochemical staining demonstrated that 68 of 108 gastric cancer samples (63.0%) were positive for galectin-1 and 62 out of 108 gastric cancer samples (57.4%) were positive for VEGF. Galectin-1 expression was associated with tumor size, differentiation grade, TNM stage, lymph node metastases, and VEGF expression. VEGF expression was related to tumor size, TNM stage, and lymph node metastases. Kaplan-Meier survival analysis showed that high galectin-1 and VEGF expressions exhibited significant correlations with poor prognosis for gastric cancer patients. Multivariate analysis revealed that galectin-1 and VEGF expressions were independent prognostic parameters for the overall survival rate of gastric cancer patients. The results of the present study suggest that galectin-1 expression is positively associated with VEGF expression. Both galectin-1 and VEGF can serve as independent prognostic indicators of poor survival for gastric cancer.

Expression of serum miR-16, let-7f, and miR-21 in patients with hepatocellular carcinoma and their clinical significances.

BACKGROUND: Recent studies showed that serum microRNAs were aberrantly expressed in cancers, including hepatocellular carcinoma (HCC). Serum microRNA (miRNA) profiles in HCC have been filtered in our previous studies. In this research, some serum miRNAs were further validated and their clinical significances were analyzed. METHODS: Sera from 90 HCC patients, the subjects, and 60 non-HCC normal, the controls, were used. The expression of serum microRNAs was measured using real-time reverse transcription-polymerase chain reaction. AFP, as well as other clinical materials, were summarized from the HCC databases in our hospital. RESULTS: Serum miR-16, let-7f, and miR-21 are down-regulated in HCC while miR-98 and miR-221 are not regulated significantly. Moreover, these miRNAs are of specific clinical significance. The expression of serum miR-16 is down-regulated in the patients with a tumor more than 5 cm in diameter (p = 0.0013) and is correlated with some quantitative clinical features such as platelets (p = 0.0255), PT (p = 0.0007) and bilirubin (p = 0.0025). The expression of serum let-7f is up-regulated in the patients with a tumor more than 5 cm in diameter (p = 0.0367) and early recurrence (p = 0.0047). The expression of serum miR-21 is up-regulated in female patients with HCC (p = 0.0297). CONCLUSIONS: Serum miR-16, let-7f, and miR-21 are related with the biological behavior of HCC, which means that they could be considered as the potential indicators to estimate the tumor size or the recurrence of HCC.

Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

Laparotomy-Induced Peripheral Inflammation Activates NR2B Receptors on the Brain Mast Cells and Results in Neuroinflammation in a Vagus Nerve-Dependent Manner.

Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the "first responders", play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified. Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again. Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate. Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.

Aortopulmonary window with subaortic fibrous stenosis and septal defect: surgery through a minimal right vertical infra-axillary thoracotomy.

Aortopulmonary window with subaortic stenosis and ventricular septal defect is an uncommon congenital cardiac malformation that is repaired using cardiopulmonary bypass. The authors describe a 3-year-old patient on whom we performed surgery through a minimal right vertical infra-axillary thoracotomy. This minimally invasive surgery is likely to be applicable in a few cases.

Circulating microRNAs: potential biomarkers for cancer.

Cancer is the leading cause of death in the world. Development of minimally invasive biomarkers for early detection of cancer is urgently needed to reduce high morbidity and mortality associated with malignancy. MicroRNAs (miRNAs) are small regulatory RNAs that modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. Recently, miRNAs were found to be dysregulated in a variety of diseases including cancer. Emerging evidence suggests that miRNAs are involved in tumor initiation and progression. Together, the different expression profiles of miRNAs in cancer, and the stability of circulating miRNAs, make them new potentially clinical biomarkers for cancer diagnosis, classification, therapeutic decisions, and prognosis.

Hemoperfusion with HA380 in acute type A aortic dissection patients undergoing aortic arch operation (HPAO): a randomized, controlled, double-blind clinical trial.

BACKGROUND: Cardiopulmonary bypass (CPB) is an important cause of significant systemic inflammatory response syndrome (SIRS) in the surgical treatment of acute type A aortic dissection (ATAAD). In patients with arch vessel involvement, extensive surgical repairs often necessitate prolonged use of CPB and results in extensive inflammatory responses. Cytokines and chemokines released during CPB contribute to the progression of SIRS, increase perioperative complications, and negatively impact surgical outcomes. A cytokine adsorber (HA380) is expected to reduce the level of cytokines during CPB, which may decrease both intraoperative and postoperative inflammation. The purpose of this study is to investigate if HA380 is able to reduce the levels of inflammatory cytokines and decrease perioperative complications in ATAAD patients undergoing CPB and deep hypothermic circulatory arrest (DHCA). METHODS: This study is a single-center, randomized, controlled, double-blind clinical trial. The study aims to recruit 88 patients with ATAAD and aortic arch involvement who will undergo CPB and DHCA to repair the dissected aorta. Patients will be randomized equally into the CPB/DHCA only group (control group) and the CPB/DHCA + HA380 hemoperfusion group (intervention group), with 44 patients each. Patients in the control group will undergo CPB and DHCA only, while patients in the intervention group will undergo continuous hemoperfusion with HA380, in addition to CPB and DHCA. The primary outcome is a composite of major perioperative complications. The secondary outcomes include related inflammatory markers, coagulation parameters, and minor perioperative complications. To comprehensively evaluate the effect of hemoperfusion on the perioperative outcomes, we will also determine if there are differences in perioperative all-cause mortality, length of ICU stay, and total hospitalization costs. DISCUSSION: In the current trial, hemoperfusion will be applied in patients undergoing CPB and DHCA for repair of the aorta involving the aortic arch. This trial aims to test the safety and efficacy of our hemoperfusion device (HA380) in such settings. Upon completion of the trial, we will determine if HA380 is effective in reducing perioperative proinflammatory cytokine levels. Further, we will also verify if reduction in the proinflammatory cytokine levels, if present, translates to improvement in patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04007484 . Registered on 1 July 2019 (retrospectively registered).

[The clinical effect and long-term follow-up of minimally invasive direct coronary artery bypass grafting via left anterior small thoracotomy].

OBJECTIVE: To estimate the clinical effect and long-term follow-up of minimally invasive direct coronary artery bypass grafting (MIDCAB) via left anterior small thoracotomy. METHODS: MIDCAB via left anterior small thoracotomy approach was performed in 38 cases of coronary artery disease with single or multi-vessel involvement from January 2002 to October 2006. There were 25 males and 13 females with a mean age of (63.3 +/- 11.1) years old. The left internal mammary artery (LIMA) was harvested under direct vision or with the assistance of thoracoscopy. After heparinization the pericardium was directly opened to expose the target vessels. The coronary artery bypass grafting was completed on beating heart. RESULTS: The procedure were smoothly completed in all the 38 cases. The LIMA was anastomosed to the left anterior descending artery (LAD) or the diagonal artery in 20 cases, while two bypass grafts were performed in 8 cases (including 3 cases of sequential grafting and 5 cases of LIMA-radial artery Y-shaped grafting). Hybrid procedure was performed on 10 patients. There were no serious postoperative complications and operative deaths found. All the 38 cases except one were followed for 26 to 82 (53.2 +/- 28.5) months and no myocardial infarction or death occurred. NYHA class were I in 26 cases and II in 12 cases. There were 3 recurrence of angina, 2 patients relieved their symptoms with medication while 1 patient received stent implantation because of anastomose stenosis confirmed by coronary angiography 2 years after surgery. CONCLUSIONS: MIDCAB via left anterior small thoracotomy has low rate of mortality and adverse cardiac events. The long-term follow-up is good.

[Assessment of early mortality risk factors undergoing coronary artery bypass graft surgery].

OBJECTIVE: To analyze early mortality risk factors and clinical characteristics in our patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Clinical data of 310 consecutive patients undergoing CABG from January 2005 to March 2007 were collected. Twenty-two risk factors were evaluated by univariate and multivariate Logistic stepwise regression analysis. RESULTS: Univariate statistical analysis revealed that factors significantly correlated with early death were 12 variables including age, diabetes, neurological dysfunction, old myocardial infarction, acute myocardial infarction, ejection function, left main artery stenosis, emergency procedure, cardiopulmonary bypass time, aortic cross-calming time, and mechanical ventilation time. Logistic stepwise regression analysis showed that emergency procedure, ejection function, age, cardiopulmonary bypass time, and mechanical ventilation time were independent risk factor of early mortality after procedure. CONCLUSION: Emergency procedure, ejection function, age, cardiopulmonary bypass time, and mechanical ventilation time are independent risk factors of early mortality after CABG procedure.

[The predictive values of EuroSCORE of early mortality in coronary artery bypass grafting patients].

OBJECTIVE: To verify the predictive value of EuroSCORE of early mortality in coronary artery bypass grafting (CABG) patients. METHOD: From January 2005 to March 2007, 310 consecutive patients were operated with CABG. Detailed data for the EuroSCORE risk factor were collected and all patients were scored according to the EuroSCORE additive model, retrospectively or prospectively. Expected or predicted mortality was calculated for individual patients using the EuroSCORE algorithms, arranged sequentially in order of predicted score. The population was divided into three clinically relevant risk categories according to the range of predicted mortality rate. Expected mortality was compared to observed or actual mortality for each risk category. Mortality was defined as death from any cause within 30 days of operation or within the same hospital admission. RESULTS: Preoperative overall patients: low-risk group was 25.2% (78/310), middle-risk group was 48.4% (150/310), high-risk group was 26.4% (82/310). In the EuroSCORE model, predicted mortality was 1.4% for low-risk group, 2.7% for middle-risk group, 7.4% for high-risk group, and 3.6% for overall patients. Actual mortality was 0, 1.3% and 3.7% respectively, overall early mortality was 1.6%. Area under the ROC curve was 0.78. CONCLUSION: The EuroSCORE yield good predictive value for hospital mortality of patients undergoing CABG, especially in off-pump CABG.

Hyperpatulones A-F, polycyclic polyprenylated acylphloroglucinols from Hypericum patulum and their cytotoxic activities.

Six new compounds, hyperpatulones A-F (1-6), along with ten additional known related derivatives (7-16), were isolated from Hypericum patulum (Guttiferae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR), X-ray crystallography, electronic circular dichroism (ECD) spectroscopy and Rh2(OCOCF3)4-induced ECD. All compounds were tested for their cytotoxic activities on human HepG-2, HeLa, MCF-7, and A549 cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compound 5 exhibited significant cytotoxicities against HepG-2, HeLa and A549 cell lines with IC50 values of 9.52 ± 0.27, 11.87 ± 0.22 and 12.63 ± 0.12 µM, respectively.

Isolation and identification of new prenylated acetophenone derivatives from Acronychia oligophlebia.

Three new prenylated acetophenone derivatives, acronyculatin P (1), acronyculatin Q (2), and acronyculatin R (3) were isolated from the leaves of Acronychia oligophlebia. Their structures were identified by extensive analyses of spectroscopic data (IR, UV, ESI-HRMS, 1D and 2D NMR) and comparison with the literatures. In addition, the cytotoxic activity against MCF-7 cells of the compounds were evaluated by the MTT assay and the IC50 values were 56.8, 40.4 and 69.1 µM, respectively.

Baseline Peripheral Blood Leukocytosis Is Negatively Correlated With T-Cell Infiltration Predicting Worse Outcome in Colorectal Cancers.

We aimed to explore the prognostic value of blood leukocyte and to generate a predictive model to refine risk stratification for colorectal cancers. 6,558 patients with colorectal cancers were identified eligible respectively in Fudan University Shanghai Cancer Center (FUSCC) between May, 2008 and October, 2016. Then the entire set is divided into a training set and a testing set. The prognostic value of pretreatment white blood cell count and clinicopathologic parameters in the context of tumor-infiltrating lymphocytes (TIL) and neutrophils was investigated. Conventional leukocytosis (≥10,000/µl) was significantly associated with decreased overall survival (OS) and disease-free survival (DFS) (p < 0.05). In fact, moderately elevated leukocyte (≥7,500/µl) has also been identified as an independent prognostic factor for survivals in the training, testing, and entire sets, respectively. And leukocytosis correlated with advanced T-stage (p < 0.001), M-stage (p < 0.001), poor differentiation tumor (p = 0.023) and Glasgow prognostic score, even predicted for worse relapse postoperatively (p = 0.001) and resistance to chemotherapy. In addition, nomograms on OS and DFS were established according to leukocytosis and other significant factors, demonstrating a great prediction accuracy. Importantly, pretreatment leukocytosis had a significantly lower intra-tumor CD3+ and CD8+ TIL infiltration (p < 0.001 and p = 0.033), whereas low CD3+ and CD8+ TIL expression in tumor were associated with worse OS and DFS (p = 0.02 and p = 0.015). In conclusion, our study validates leukocytosis as an independent prognostic factor in colorectal cancers. Our data provide for the first-time vital insight on the correlation of peripheral pretreatment leukocytosis with the tumor-infiltrating cells contexture and might be relevant for future risk stratification.

Osteoglycin (OGN) reverses epithelial to mesenchymal transition and invasiveness in colorectal cancer via EGFR/Akt pathway.

BACKGROUND: Many types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, and the role of OGN in cancer progression. METHODS: The tissue microarray staining was performed and the relevance between OGN expression and oncologic outcomes was performed using Cox regression analysis. The effect of OGN on cell proliferation and tumorigenesis was examined in vitro and in vivo. Immunoprecipitation assay, immunofluorescence analysis and internalization assay were used for mechanistic study. RESULTS: Patients with high expression of OGN were associated with a profound longer survival in CRC and the high serum OGN level was also indicative of fewer recurrences consistently. In colon cancer cells, OGN increased dimerization of EGFR, then triggered EGFR endocytosis and induced the recruitment of downstream components of the EGFR internalization machinery (Eps15 and epsin1). Above all, OGN reduced Zeb-1 expression via EGFR/Akt leading to inhibition of epithelial-mesenchymal transition. As results, in vitro and in vivo, the OGN expression was demonstrated to reduce cell proliferation, inhibit invasion of colon cancer cells then impede cancer progression. CONCLUSIONS: There is a positive association between OGN level and prolonged survival in CRC. OGN plays a restrictive role in colorectal cancer progression by reduced activation of EGFR/AKT/Zeb-1.

ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic Survival in Colorectal Cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are significantly correlated with a favorable prognosis, such as CD8+ lymphocytes, which are also called tumor-reactive lymphocytes. However, not all tumor-infiltrating T cells confer benefit to patients. Therefore, it is of substantial benefit to identify a biomarker to demarcate these tumor-reactive lymphocytes. METHODS: We investigated whether ITGAE could be used to discriminate reactive CD8+ lymphocytes in colorectal cancer (CRC). TCGA colorectal cancer data sets (n1 = 492, n2 = 386) and FUSCC set (n3 = 276) were used in this study. Further phenotyping of ITGAE+ cells and the mechanistic basis were investigated. FINDINGS: In the training and testing sets from TCGA, ITGAE expression, which is strongly correlated with cytotoxic T cell markers (CD8/CD3/PD1), independently predicted longer disease-free survival (DFS) and overall survival (OS). In line with this, the association between ITGAE+ lymphocytes and survival has been confirmed in the FUSCC cohort for validation (P = .026). ITGAE + cells in the series always co-stained with CD8 were preferentially located in the tumor. Interestingly, ITGAE+ lymphocytes tended to associate with the epithelial-mesenchymal transition (EMT) with decreased Snail and increased E-cadherin expression accompanied. Finally, gene set enrichment analysis showed that immune activation was significantly enriched in the high ITGAE+ TIL group, accompanied by enriched EMT-related pathways. INTERPRETATION: Because of the specified expression of tumor-reactive CD8+ T-cells, ITGAE may be a promising biomarker for the rapid identification of immune infiltration in CRC.

Osteoglycin-induced VEGF Inhibition Enhances T Lymphocytes Infiltrating in Colorectal Cancer.

BACKGROUND: OGN could modify tissue inflammation and immune response via local and circulating innate immune cells, which was suggestive of a reciprocal relationship between OGN and T cell infiltration in cancer. Hence, we aim to measure the OGN expression patterns and immune cells response in colorectal cancer(CRC). METHODS: This study enrolled three independent sets of patients from TCGA and the Fudan University Shanghai Cancer Center(FUSCC). The effect of OGN on T cell infiltration and the mechanism were examined in vitro and in vivo. FINDINGS: Tumor OGN expression levels were positively associated with CD3, CD8, and PTPRC expressions in the training and testing sets from TCGA, respectively. In validation set from FUSCC, OGN expression level also paralleled positively with CD8+ cell density in colorectal cancer tissue (p < .001). For a unit decrease in outcome quartile categories, multivariable OR in the lowest (vs highest) OGN expression was 0.17 (95% CI 0.08-0.33). Consistently, immunofluorescence validated that OGN was preferentially expressed with CD8+ cells in both normal epithelium and cancer tissue. Xenograft tumors arising from MC38 cells with OGN-over-expression displayed a significant increase in CD8+ cells recruitment. Hence, high expression of OGN was associated with a profound longer survival (P = .009). In mechanism, elevated OGN expression inhibited the activation of the transcriptional genes HIF-1α in CRC cells, then significantly impeded the expression of VEGF. As a result of this, T cell tumor infiltration was reduced. INTERPRETATION: OGN expression is positively associated with CD8+ cell density in colorectal cancer tissue, suggesting a possible influence of OGN expression on tumor reactive T cells in the tumor niche. FUND: No.

Terpenoids from the stems of Celastrus hindsii and their anti-RSV activities.

Two new oleanane-type triterpenoids (1-2), a new ursane-type triterpenoid (3), and a new podocarpane-type diterpenoid (4), together with 20 known compounds (5-24) were isolated from the stems of Celastrus hindsii Benth. Their structures were identified on the basis of the spectral data (HRESIMS, IR, UV, 1D, and 2D NMR) and the absolute configurations were determined by comparison of experimental and calculated ECD data. The structures of 1 and 4 were further confirmed by single crystal X-ray diffraction analysis. In addition, all compounds were evaluated for their in vitro antiviral activities against respiratory syncytium virus (RSV) using cytopathic effect (CPE) reduction assay. Compounds 7, 10, 11, 19 and 24 exhibited obvious anti-RSV activity with IC50 values from 1.55 to 6.25 µM.