PARP1 bound to XRCC2 promotes tumor progression in colorectal cancer.

BACKGROUND: By complexing poly (ADP-ribose) (PAR) in reaction to broke strand, PAR polymerase1 (PARP1) acts as the key enzyme participated in DNA repair. However, recent studies suggest that unrepaired DNA breaks results in persistent PARP1 activation, which leads to a progressively reduce in hexokinase1 (HK1) activity and cell death. PARP-1 is TCF-4/ß-A novel co activator of gene transactivation induced by catenin may play a role in the development of colorectal cancer. The molecular mechanism of PARP1 remains elusive. METHODS: 212 colorectal cancer (CRC) patients who had the operation at our hospital were recruited. PARP1 expression was evaluated by immunohistochemistry. Stable CRC cell lines with low or high PARP1 expression were constructed. Survival analysis was computed based on PARP1 expression. The cell proliferation was tested by CCK-8 and Colony formation assay. The interaction of PARP1 and XRCC2 was detected by immunoprecipitation (IP) analysis. RESULTS: Compared with matching adjacent noncancerous tissue, PARP1 was upregulated in CRC tissue which was correlated with the degree of differentiation, TNM stage, depth of invasion, metastasis, and survival. In addition, after constructing CRC stable cell lines with abnormal expression of PARP1, we found that overexpression of PARP1 promoted proliferation, and demonstrated the interaction between PARP1 and XRCC2 in CRC cells through immunoprecipitation (IP) analysis. Moreover, the inhibitor of XRCC2 can suppress the in vitro proliferation arousing by upregulation of PARP1. CONCLUSIONS: PARP1 was upregulated in CRC cells and promoted cell proliferation. Furthermore, the expression status of PARP1 was significantly correlated with some clinicopathological features and 5-year survival.

Survival Benefit of Synchronous Lenvatinib Combined PD-1 Inhibitors for Advanced Hepatocellular Carcinoma Beyond Oligometastasis.

Purpose: Strategies therapy for hepatocellular carcinoma (HCC) beyond oligometastasis are limited. The optimal sequence of systemic treatment for advanced HCC is not yet clear. Our study aims to evaluate the effectiveness of simultaneous lenvatinib combined PD-1 inhibitor on advanced HCC beyond oligometastasis. Patients and Methods: A total of 232 patients were enrolled in our retrospective study. Patients divided into three groups. (a) Lenvatinib plus simultaneous PD-1 inhibitor (Simultaneous group, n=58); (b) patients received PD-1 inhibitor before the tumor progression with continued lenvatinib administration (Before PD group, n=77); (c) patients received PD-1 inhibitor after the tumor progression (After PD group, n=97). To analyze overall survival (OS) and progression-free survival (PFS) among the three groups. Results: The estimated 6-, 12-, 18- and 24-mon OS for Simultaneous group patients were 100%, 93.1%, 63.4%, 48.3%, whereas the OS rates were 100%, 78%, 36.3%, 23.6% in Before PD group, and 99%, 61.2%, 22.1%, 7.5% in After PD group. The OS rates were obviously improved with the use of simultaneous PD-1 inhibitor among the three groups (P <0.001). The estimated 3-, 6-, 9- and 12-month PFS rates for patients were 89.6%, 44.8%, 24.6%, 6% in After PD group, 90.9%, 59.7%, 27.3%, 12.4% in Before PD group and 98.3%, 81%, 51.7%, 39.7% in Simultaneous group, respectively. PFS rate was significantly different among the three groups (P <0.001). Conclusion: Synchronous administration of lenvatinib and PD-1 inhibitors improved survival rate significantly. The synchronous combination could represent a promising strategy in HCC beyond oligometastasis.

Efficacy and Safety of Radical Resection of Rectal Cancer Combined with Selective Lateral Lymph Node Dissection in the Treatment of Low Rectal Cancer under Meta-analysis.

Rectal cancer mostly occurs in the middle and low position in China, and many anatomical evidence has confirmed that Lateral Lymph Node Metastasis (LLNM) exists in middle and low rectal cancer. Laparoscopic surgery can penetrate into the pelvic cavity and magnify and narrow the visual field, which is helpful for lymph node dissection and vascular nerve protection, while it has minimally invasive characteristics and is considered to be more suitable for LLND. Relevant articles published from January 2000 to May 2022 are searched using "Rectal cancer, Lateral lymph node dissection, Radical resection of rectal cancer, Low rectal cancer, Laparoscopic therapy, Treatment of rectal cancer" as test terms, analyzed and assessed using Rev Man 5.3 software and Stata software to assess the risk bias of included references, and heterogeneity among each study is evaluated using Q test and heterogeneity (I2). The experimental results show that there is no heterogeneity among the studies (I2 = 8.46%). The heterogeneity of lymphatic metastasis in the included literature is evaluated, and the results show that there is heterogeneity between the studies (I2 = 52.06%).

[Effects of high volume hemofiltration on postoperative multiple organ dysfunction syndrome in severe abdominal infection patients].

AIM: To evaluate the clinical efficacy of high-volume hemofiltration (HVHF) on treating postoperative multiple organ dysfunction syndrome in severe abdominal infection patients. METHODS: Data of 17 severe abdominal infection patients treated with HVHF were collected and the differences on oxygenation indices, APACHE-II scores before and after HVHF therapy were observed. RESULTS: After the first HVHF treatment, the oxygenation index improved, and the APACHE-II scores, TNF-alpha, IL-6, and IL-8 decreased significantly (P<0.05). After several HVHF treatments, the oxygenation index improved, and the APACHE-II scores decreased significantly (P<0.05). CONCLUSION: HVHF can improve both the respiratory function and vital signs of severe sepsis patients and relieve the severity of the illness.