Neoadjuvant Camrelizumab for Non-Small Cell Lung Cancer: A Retrospective Multicenter, Real-World Study (CTONG2004).

BACKGROUND: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. METHODS: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. RESULTS: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1-6). The median interval from the last dose to surgery was 33 days (range 13-102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5-1200 mL), and the median operative time was 3.0 h (range 1.5-6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4-85.0%), and the disease control rate was 93.8% (95% CI 86.9-97.7%). Twenty-six patients (27.1%, 95% CI 18.5-37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. CONCLUSION: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted.

Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α.

OBJECTIVE: To explore the efficacy of ursolic acid in sensitizing colon cancer cells to chemotherapy under hypoxia and its underlying mechanisms. METHODS: Three colon cancer cell lines (RKO, LoVo, and SW480) were used as in vitro models. 5-Fluorouracil (5-FU) and oxaliplatin were used as chemotherapeutic drugs. Cell viability and apoptosis were tested to evaluate the sensitivity of colon cancer cells to chemotherapy. The transcription and expression levels of hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1), and vascular endothelial growth factors (VEGF) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting. Cycloheximide and MG132 were used to inhibit protein synthesis and degradation, respectively. In vitro tube formation assay was used to evaluate angiogenesis. RESULTS: We demonstrated the chemosensitizing effects of ursolic acid with 5-FU and oxaliplatin in three colon cancer cell lines under hypoxia. This effect was correlated to its inhibition of MDR1 through HIF-1α. Moreover, ursolic acid was capable of inhibiting HIF-1α accumulation with little effects on its constitutional expression in normoxia. In addition, ursolic acid also down-regulated VEGF and inhibited tumor angiogenesis. CONCLUSIONS: Ursolic acid exerted chemosensitizing effects in colon cancer cells under hypoxia by inhibiting HIF-1α accumulation and the subsequent expression of the MDR1 and VEGF.

Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro.

OBJECTIVE: To investigate the proliferation-inhibiting and apoptosis-inducing effects of ursolic acid (UA) and oleanolic acid (OA) on multi-drug resistance (MDR) cancer cells in vitro. METHODS: UA and OA in different concentrations (0-100 µmol/L) were added separately to cultures of different cancer cell lines, including the human colon cancer cell lines SW480 and SW620, human acute myelocytic leukemia cancer cell lines HL60 and HL60/ADR, human chronic myelogenous leukemia cell lines K562 and K562/ADR, and the human breast cancer cell lines MCF-7 and MCF-7/ADR. Effects of UA and OA on cell proliferation were detected by 3-(4,5-dimethyl-2-thiazole)-2-5-biphenly-tetrazole bromide (MTT) method and effects on cell apoptosis were tested by flow cytometry (FCM) and Western blot at 24, 48, and 72 h after treatment. RESULTS: Both UA and OA showed significant inhibition on parent and MDR cell lines in a time- and concentration-dependent manner; the drug-resistant multiple of them on K562 and K562/ADR as well as on HL60 and HL60/ADR was 1; the effects of UA were better than those of OA in inhibiting cell growth of solid colonic cancer and breast cancer. After SW480 cells were treated by UA at the concentrations of 0-40 µmol/L for 48 h, FCM showed that annexin V (AV) positive cells and hypodiploid peak ratio increased along with the increase in the drug's concentrations; and Western blot found that expressions of Bcl-2, Bcl-xL and survivin decreased in a concentration-dependent manner. CONCLUSIONS: Both UA and OA have antitumor effects on cancer cells with MDR, and the optimal effect is shown by UA on colonic cancer cells. Also, UA shows cell apoptosis-inducing effect on SW480, possibly by way of down-regulating the expressions of apoptosis antagonistic proteins, Bcl-2, Bcl-xL, and survivin.

Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway.

OBJECTIVE: To investigate the effects of ursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate the effects of ursolic acid on the growth and apoptosis of HT-29 cells. Western blot analysis was applied to investigate the inhibitory effects of ursolic acid on the phosphorylation of the epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and the activity of B cell leukemia-2 (Bcl-2), B cell leukemia-xL (Bcl-xL), caspase-3, and caspase-9. RESULTS: Ursolic acid inhibited the growth of HT-29 cells in dose- and time-dependent manners. The median inhibition concentration (IC50) values for 24, 48, and 72 h treatment were 26, 20, and 18 micromol/L, respectively. The apoptotic rates of 10, 20, and 40 micromol/L ursolic acid treatments for 24 h were 5.74%, 14.49%, and 33.05%, and for 48 h were 9%, 21.39%, and 40.49%, respectively. Ursolic acid suppressed the phosphorylation of EGFR, ERK1/2, p38 MAPK, and JNK, which is well correlated with its growth inhibitory effect. 10, 20, and 40 micromol/L ursolic acid significantly inhibited the proliferation of EGF-stimulated HT-29 cells (P<0.05). Cell proliferation was most significantly inhibited when treated with 10 and 20 micromol/L ursolic acid combined with 200 nmol/L AG 1478 or 10 micromol/L U0126 (P<0.01). Besides, it also down-regulated the expression of Bcl-2 and Bcl-xL and activated caspase-3 and caspase-9. CONCLUSION: Ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.

Clinical observation on treatment of post-craniocerebral traumatic mental disorder by integrative medicine.

OBJECTIVE: To observe the clinical efficacy of integrative medical therapy in treating post-craniocerebral traumatic mental disorder (PCT-MD). METHODS: Sixty patients with confirmed diagnosis of PCT-MD were randomly assigned to the treated group and the control group equally. All were treated by conventional comprehensive Western medicine, but to patients in the treated group, modified Xufu Zhuyu Decoction (XFZY) was additionally given and the therapeutic course for both groups was 20 days. Changes in mental symptoms were observed and recorded on the 10th and 20th day and clinical efficacy as well as cranial CT image was estimated after termination of the treatment. RESULTS: The clinical effective rate in the treated group and the control group was 96.67% and 83.30% respectively. Comparison between them showed significant difference (P<0.05). Significant differences were also shown in the comparisons between the two groups in improving mental symptoms, either on the 10th or on the 20th day (P<0.05 and P<0.01 respectively), and in post-treatment cranial CT image (P<0.05). CONCLUSION: Better efficacy could be obtained by integrative medical therapy in treating PCT-MD.

[Experimental study on treating hyperlipidemic fatty liver with Taizhi'an capsule].

OBJECTIVE: To observe the effects of Taizhi'an capsule in treatment of hyperlipidemic fatty liver. METHOD: The model rats were induced by feeding high caloric diet for 8 weeks, then fifty rats were randomly divided into five groups, and each group had ten rats, the Taizhi'an groups (high dose 1 000 mg x kg(-1), middle dose 500 mg x kg(-1), low dose 250 mg x kg(-1)), the Yishanfu group and the model group. Liver index (liver weight/body weight), liver function, blood lipid, liver lipid, the content of MDA and SOD in liver were assayed after therapy, and observe Pathologic changes in rats liver. RESULT: Liver index, blood lipid, liver lipid, liver function increased significantly (P < 0.001) in model rats, and the content of SOD in liver decreased significantly (P < 0.05), Liver histology expressed mild to moderate fat denaturation; After being treated with high and middle dose of Taizhi'an capsule for six weeks, blood lipid, liver function decreased significantly (P < 0.001), and liver lipid decreased significantly (P < 0.001, P <0.05), the content of SOD in liver increased significantly (P < 0.05), meanwhile liver histology was closed to normal. CONCLUSION: Taizhian capsule is effective in the treatment of hyperlipidemic induced fatty liver.