New nomogram for predicting lymph node positivity in pancreatic head cancer.

Background: Pancreatic cancer is one of the most malignant cancers worldwide, and it mostly occurs in the head of the pancreas. Existing laparoscopic pancreaticoduodenectomy (LPD) surgical techniques have has undergone a learning curve, a wide variety of approaches for the treatment of pancreatic cancer have been proposed, and the operation has matured. At present, pancreatic head cancer has been gradually changing from "surgeons' evaluation of anatomical resection" to "biologically inappropriate resection". In this study, the risk of lymph node metastasis in pancreatic head cancer was predicted using common preoperative clinical indicators. Methods: The preoperative clinical data of 191 patients with pancreatic head cancer who received LPD in the First Affiliated Hospital of Jilin University from May 2016 to December 2021 were obtained. A univariate regression analysis study was conducted, and the indicators with a significance level of P<0.05 were included in the univariate logistic regression analysis into multivariate. Lastly, a nomogram was built based on age, tumor size, leucocyte,albumin(ALB), and lymphocytes/monocytes(LMR). The model with the highest resolution was selected by obtaining the area under a curve. The clinical net benefit of the prediction model was examined using decision curve analyses.Risk stratification was performed by combining preoperative CT scan with existing models. Results: Multivariate logistic regression analysis found age, tumor size, WBC, ALB, and LMR as five independent factors. A nomogram model was constructed based on the above indicators. The model was calibrated by validating the calibration curve within 1000 bootstrap resamples. The ROC curve achieved an AUC of 0.745(confidence interval of 95%: 0.673-0.816), thus indicating that the model had excellent discriminative skills. DCA suggested that the predictive model achieved a high net benefit in the nearly entire threshold probability range. Conclusions: This study has been the first to investigate a nomogram for preoperative prediction of lymphatic metastasis in pancreatic head cancer. The result suggests that age, ALB, tumor size, WBC, and LMR are independent risk factors for lymph node metastasis in pancreatic head cancer. This study may provide a novel perspective for the selection of appropriate continuous treatment regimens, the increase of the survival rate of patients with pancreatic head cancer, and the selection of appropriate neoadjuvant therapy patients.

Combining Gemcitabine-Loaded Macrophage-like Nanoparticles and Erlotinib for Pancreatic Cancer Therapy.

Pancreatic cancer is a lethal malignancy with a dismal prognosis. Gemcitabine is currently used to treat pancreatic cancer, but it is limited by significant toxicity. Clinical trials on the combination of gemcitabine and erlotinib reported unsatisfactory outcomes along with concerns of toxicity. The encapsulation of chemotherapy drugs in polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) can alleviate toxicity through targeted delivery and sustained release. In addition, camouflaging the NPs with a macrophage membrane can evade the immune system and further improve tumor homing. We designed gemcitabine-loaded PLGA NPs with a macrophage membrane coating (MPGNPs) to reduce drug toxicity and increase the accumulation in the tumor. The combination of MPGNPs and erlotinib synergistically inhibited pancreatic cancer cell proliferation in vitro and in vivo by targeting the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling pathways. The MPGNPs were also able to evade phagocytosis and achieve passive targeting to the pancreatic tumors. The combination of MPGNPs and erlotinib showed synergistic anti-tumor efficacy in vitro and in vivo. This study provides a proof-of-concept for treating pancreatic cancer with a combination of MPGNPs and erlotinib.

Ataxia telangiectasia mutated inhibitor-loaded copper sulfide nanoparticles for low-temperature photothermal therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and is ranked the sixth most common neoplasm and the third leading cause of cancer-related deaths. Photothermal therapy (PTT) for thermal ablation of local tumors has recently emerged as a therapeutic strategy. However, the relatively high temperature of over 50 °C may lead to unexpected heat-related damage to tumor-adjacent normal tissues. Herein, we designed and synthesized ataxia telangiectasia mutated (ATM) inhibitor loaded hollow-structured CuS NPs with surface modification with anti-TGF-ß antibody (CuS-ATMi@TGF-ß NPs). CuS-ATMi@TGF-ß NPs are highly photo-stable, can release encapsulated drugs, and increase the temperature to an effective level in a near-infrared (NIR)-responsive manner. Moreover, CuS-ATMi@TGF-ß NPs specifically target tumors and thereby significantly inhibit tumor growth on contribution to synergistic low-temperature PTT and chemotherapy. This system not only achieved low-temperature PTT but also resulted in reduced damage to normal tissues. Modification with anti-TGF-ß antibody enhanced target specificity and immune activation. The combination of PTT and ATM inhibitor showed synergistic effects and significantly attenuated the growth of the HCC via down regulation of heat shock protein (HSP). CuS-ATMi@TGF-ß NPs are a highly promising platform for targeted tumor ablation via hyperthermia-mediated tumor death with minimal damage to normal tissues at a low temperature. STATEMENT OF SIGNIFICANCE: We constructed ataxia telangiectasia mutated (ATM) inhibitor-loaded hollow-structured CuS NPs with surface modification with anti-TGF-ß antibody (CuS-ATMi@TGF-ß NPs). CuS-ATMi@TGF-ß NPs not only achieved low-temperature photothermal therapy (PTT) but also resulted in reduced damage to normal tissues and sufficient biocompatibility. The modification with anti-TGF-ß antibody enhanced targeted specificity, cell endocytosis, and immune activation. In addition, the combination of PTT and ATM inhibitor synergistically attenuated the growth of the HCC via downregulation of heat shock protein (HSP). This study provided proof-of-concept for the ATM inhibitor that mediated low-temperature PTT with a potential for future clinical applications.