No abstract

Background: Patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) may have a better prognosis and may be eligible for non-operative management. The aim of this research was to identify variables for predicting pCR in rectal cancer patients after nCRT and to define clinical risk factors for poor outcome after pCR to nCRT and radical resection in rectal cancer patients. Methods: A retrospective review was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Non-metastatic rectal cancer patients who received radical resection after neoadjuvant chemoradiotherapy were included in this study. Multivariate analysis of the association between clinicopathological characteristics and pCR was performed, and a logistic regression model was used to identify independent predictors for pCR. A nomogram based on the multivariate logistics regression was built with decision curve analyses to evaluate the clinical usefulness. Results: A total of 6,555 patients were included in this study. The proportion of patients with pCR was 20.5% ( n = 1,342). The nomogram based on multivariate logistic regression analysis showed that clinical T4 and N2 stages were the most significant independent clinical predictors for not achieving pCR, followed by mucinous adenocarcinoma and positive pre-treatment serum CEA results. The 3-year overall survival rate was 92.4% for those with pCR and 88.2% for those without pCR. Among all the pCR patients, mucinous adenocarcinoma patients had the worst survival, with a 3-year overall survival rate of 67.5%, whereas patients with common adenocarcinoma had an overall survival rate of 93.8% ( P < 0.001). Univariate and multivariate analyses showed that histology and clinical N2 stage were independent risk factors. Conclusion: Mucinous adenocarcinoma, positive pre-treatment serum CEA results, and clinical T4 and N2 stages may impart difficulty for patients to achieve pCR. Mucinous adenocarcinoma and clinical N2 stage might be indicative of a prognostically unfavorable biological tumor profile with a greater propensity for local or distant recurrence and decreased survival.

Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor‐infiltration of immune cells and immunosuppressive tumor microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes and inhibit negative immune regulators will greatly amplify immunotherapy outcome, which is however very rare. Herein, a new kind of semiconducting polymer (SP) nanoparticles is developed, featured with surface‐mimicking protein secondary structure (SPSS NPs) for self‐synergistic cancer immunotherapy by combining immunogenic cell death (ICD) and immune checkpoint blockade therapy. The SPs with excellent photodynamic property are synthesized by rational fluorination, which can massively induce ICD. Additionally, the peptide antagonists are introduced and self‐assembled into β‐sheet protein secondary structures on the photodynamic NP surface via preparation process optimization, which function as efficient lysosome‐targeting chimaeras (LYTACs) to mediate the degradation of programmed cell death ligand‐1 (PD‐L1) in lysosome. In vivo experiments demonstrate that SPSS NPs can not only elicit strong antitumor immunity to suppress both primary tumor and distant tumor, but also evoke long‐term immunological memory against tumor rechallenge. This work introduces a new kind of robust immunotherapy agents by combining well‐designed photosensitizer‐based ICD induction and protein secondary structures‐mediated LYTAC‐like multivalence PD‐L1 blockade, rendering great promise for synergistic immunotherapy.

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).

No abstract

Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-tohot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.

Early identification of metastatic or recurrent colorectal cancer (CRC) patients who will be sensitive to FOLFOX (5‐FU, leucovorin and oxaliplatin) therapy is very important. We performed microarray meta‐analysis to identify differentially expressed genes (DEGs) between FOLFOX responders and nonresponders in metastatic or recurrent CRC patients, and found that the expression levels of WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while the expression levels of IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders. Subsequent functional annotation showed that DEGs were significantly enriched in autophagy, ErbB signaling pathway, mitophagy, endocytosis, FoxO signaling pathway, apoptosis, and antifolate resistance pathways. Based on those candidate genes, several machine learning algorithms were applied to the training set, then performances of models were assessed via the cross validation method. Candidate models with the best tuning parameters were applied to the test set and the final model showed satisfactory performance. In addition, we also reported that MLKL and CCDC124 gene expression were independent prognostic factors for metastatic CRC patients undergoing FOLFOX therapy.

Alpha-fetoprotein (AFP)-producing adenocarcinoma from the gastrointestinal tract (APA-GI) is a rare type of highly malignant tumor with a poor prognosis. It may originate from any site along the GI tract with similar clinicopathological characteristics. As limited research had ever described the characteristics of APA-GI, the present article intends to systemically investigate the clinicopathological characteristics of APA-GI from a single center's retrospective study to deepen the understanding of the disease. A total of 177 patients pathologically diagnosed with APA-GI between 2010 and 2017 at the Second Affiliated Hospital of Zhejiang University, School of Medicine, were included. Also, clinical data of 419 gastric cancers and 609 colorectal cancers from The Cancer Genome Atlas database were also extracted. Clinical information of patients from Second Affiliated Hospital of Zhejiang University, School of Medicine, was collected, and a median follow-up of 14.5 months was performed to investigate clinical characteristics of APA-GI. For the pathological characteristics of APA-GI, hematoxylin–eosin sections were reviewed, and immunohistochemistry of AFP was performed. The results showed that the primary tumor could develop through the whole GI tract, including the esophagus (0.6%), stomach (83.1%), duodenum (1.1%), ileum (0.6%), appendix (0.6%), colon (5.1%), and rectum (7.9%). Hepatoid adenocarcinoma is the main pathological feature of APA-GI. AFP expression level in tumor tissue was not strictly associated with serum AFP or hepatoid differentiation. The prognosis of APA-GI was worse than that of common adenocarcinoma of the GI tract and liver metastasis, and high AFP levels suggest poor prognosis in patients with APA-GI. Therefore, the present study was the first research to systemically explore the clinicopathological characteristics of APA-GI. APA-GI occurs through the whole GI tract with a significantly worse prognosis than common adenocarcinoma of GI. APA-GI should be regarded as one kind of disease for its similar clinicopathological characteristics within patients.