Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

BACKGROUND: Among malignant tumors, lung cancer has the highest mortality rate. Small cell lung cancer (SCLC) is a kind of malignant lung cancer. Its doubling time is very fast. Patients are prone to drug resistance during treatment, and their condition often deteriorates rapidly after recurrence. Except for topotecan, there is a lack of effective second-line single-agent chemotherapy. This study aims to analysis the efficacy and safety of irinotecan (CPT-11) in the second-line treatment of refractory and relapsed SCLC. METHODS: A total of 107 SCLC patients were collected from the Department of Oncology, Jilin Guowen Hospital, who were diagnosed from April 2012 to March 2020, relapsed within 6 months after first-line treatment, and received second-line chemotherapy with single-agent CPT-11. Follow-up until November 2020, calculate the patient's progression free survival (PFS) and overall survival (OS), and summarize the effects and adverse reactions of CPT-11 chemotherapy. RESULTS: The patient's median PFS was 3.8 (3.4-4.4) months, median OS was 8.1 (6.5-10.9) months, objective response rate (ORR) was 16.82% (18/107), and DCR was 55.14% (59/107). The incidence of grade 3-4 adverse reactions in patients was relatively low. Among them, neutropenia was 13.08%, delayed diarrhea was 7.48%, nausea and vomiting was 17.76%, and liver function impairment was 6.54%. The influencing factors of PFS in single-agent CPT-11 second-line chemotherapy were gender (P=0.001), NSE (P=0.029), and effusion (P=0.040). While the influencing factors of OS were NSE level only (P=0.033). CONCLUSIONS For patients with refractory relapsed SCLC, CPT-11 single-agent second-line chemotherapy has a certain effect, is well tolerated, and is worthy of promotion.
.

Aim To explore the mechanism of hepatocellular carcinoma (HCC) resistance to aspirin and its anti-cancer effect, so as to provide new ideas and potential possibilities for clinical prevention and treatment. Methods The HCC rat model was induced by diethylnitrosamine (DEN). The pathological changes of rat liver were observed by HE staining. The expressions of AMPK, LC3, mTOR, Beclin-1, and TFEB proteins were detected by Western blot. HCC cell proliferation was detected by CCK8 assay. Apoptosis were measured by immunofluorescence assay. Results Aspirin significantly inhibited the development of DEN-induced hepatocellular carcinoma and decreased liver/body weight ratio compared with model group. Aspirin significantly increased the expressions of LC3, Beclin-1, TFEB and AMPK. The combination of aspirin and AMPK inhibitor significantly inhibited HCC cell proliferation and increased HCC cell apoptosis. Conclusions The combination of aspirin and AMPK inhibitor can significantly enhance the inhibitory effect of aspirin on HCC.

OBJECTIVESTo explore the feasibility of DC being in vitro induced from AML cells with cytokine cocktails and their biological properties.

METHODSAML cells were cultured in either presence or absence of cytokine cocktails. DC were studied for morphology, and cytochemical and immunofluorescent staining. Functions of DC were examined by MLC, FITC-conjugated dextran uptake test, and LDH release assay. RT-PCR and FISH were used to analyze the specific fusion genes of culture-derived DC.

RESULTSClassical DC morphological changes occurred in all 15 cultured AML cells. DC-associated surface molecules such as CD(1a), CD(80), CD(86), CD(106), CD(83) and HLA-DR were upregulated (P < 0.05). The allostimulatory abilities of culture-derived DC were significantly higher than those of AML cells uncultured or cultured in the absence of cytokines (P < 0.05). Culture-derived DC only in the presence of GM-CSF + IL-4 have phagocytotic activities. CTL assay was performed in 5 of the 15 samples. At effector/target ratio of 20:1, auto-T lymphocytes primed with the culture-derived DC exhibited no more killing activity to auto-AML cells than those stimulated by IL-2 or uncultured AML cells. Culture-derived DC presenced the native AML-specific aberrant karyotype and related fusion gene.

CONCLUSIONSCytokine cocktails could in vitro induce AML cells into DC with classical morphology, immunophenotype and function. DC maturity induced by different cytokine cocktails could be variable. Culture-derived DC were originated from the native AML cells. AML cells could make the auto-T lymphocyte anergy.

Adolescent ; Adult ; Aged ; Cell Differentiation ; drug effects ; Cytokines ; pharmacology ; Dendritic Cells ; cytology ; Drug Synergism ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; In Vitro Techniques ; Interleukin-4 ; pharmacology ; Leukemia, Myeloid, Acute ; immunology ; pathology ; Male ; Middle Aged ; Monocytes ; cytology ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology