Side effects of incardronate disodium compared to pamidronate disodium in the treatment of bone metastasis pain: a systematic review and meta-analysis.

BACKGROUND: Bone metastasis is a common complication in patients with advanced malignant tumors and seriously impairs the quality of life of patients. Bisphosphonates are effective drugs for the treatment of bone metastasis pain. Incardronate disodium belongs to the 3rd generation of bisphosphonates. The efficacy and safety of bisphosphonates were explored using a systematic review and meta-analysis. METHODS: The databases PubMed (2000 to August 2021), EMBASE (2000 to August 2021), Cochrane library (August 2021), and CNKI (China National Knowledge Infrastructure, 2000 to August 2021) were searched. Randomized controlled studies involving patients being treated with incardronate for bone metastasis pain were included in the literature search. After screening and risk of bias assessment based on the Cochrane Handbook for Systematic Reviews of Interventions, Stata 16.0 software was used for analysis. RESULTS: The seven articles included in this study involved a total of 510 patients. Meta-analysis showed that there was no significant difference between incardronate and pamidronate disodium in the effectiveness of treating bone metastasis pain [odds ratio (OR) =1.03, 95% confidence interval (CI): 0.78-1.34, Z=0.188, P=0.851). The incidence of febrile adverse reactions from incardronate was significantly lower than pamidronate disodium (OR =0.58, 95% CI: 0.39-0.86, Z=-2.727, P=0.006). The total incidence of adverse reactions from incardronate was significantly lower than pamidronate disodium (OR =0.58, 95% CI: 0.40-0.85, Z=-2.851, P=0.004). DISCUSSION: The use of incardronate in the treatment of bone metastasis pain due to malignant tumors had comparable efficacy to the second-generation bisphosphonate pamidronate disodium. However, incardronate had fewer adverse reactions than pamidronate disodium.

[Effects of shRNA on Cisplatin-resistant Non-small Cell Lung Cancer Cell A549 via Silencing CCAT2].

OBJECTIVE: To investigate the effects of short hairpin RNA (shRNA) on the proliferation, invasion, apoptosis and tumor formation of non-small cell lung cancer cisplatin-resistant cell line (A549/DDP) via silencing of colon cancer associated transcript 2 ( CCAT2). METHODS: TA549/DDP cells were transfected with shRNA- CCAT2 (sh- CCAT2) or shRNA-negative control (shRNA-NC), and untransfected A549/DDP cells were used as the control group. CCAT2 mRNA expression in three groups of A549/DDP cells was detected by quantitative real-time PCR (qRT-PCR). The proliferation of three groups of A549/DDP cells treated with different mass concentrations of DDP (0-8 mg/L) was detected by MTT. According to the proliferation experiment results, 2 mg/L was selected as DDP concentration for subsequent experiments. The effects of 2 mg/L DDP treatment on the proliferation, apoptosis, and invasion ability of each group of cells (with untreated A549/DDP cells as the control group) were tested by clone formation experiments, flow cytometry analysis and Transwell experiments. The expression levels of cell proliferation marker proteins (Ki67, PCNA), apoptosis marker proteins (Caspase-3, Caspase-9) and invasion marker proteins (VEGF, MMP-14) were detected by Western blot. Nude mice were injected subcutaneously with A549/DDP cells, A549/DDP cells transfected with shRNA-NC or A549/DDP cells transfected with sh- CCAT2. DDP was intraperitoneally injected at the concentration of 2 mg per kilogram of mice body weight totally for 7 times with an interval of 3 d. A control group was injected subcutaneously with A549/DDP cells, and an equal volume of normal saline instead of DDP was injected intraperitoneally. The tumor volume was detected every 5 d for a total of 30 d. Mice were sacrificed and tumor tissues were taken out 30 d later. CCAT2 mRNA expression level in tumor tissues was detected by RT-PCR, and tumor cell apoptosis was detected by TUNEL staining. RESULTS: Compared with the control group and the shRNA-NC transfection group, the expression level of CCAT2 mRNA was decreased in sh- CCAT2 transfected A549/DDP cells ( P<0.01). The decrease degree of cell proliferation was more pronounced after treating with 2 to 8 mg/L of DDP ( P<0.01). Compared with the control group, in the three groups that treated with DDP, the formation of clones and the expression of proliferation marker proteins Ki67 and PCNA were reduce ( P<0.01), while the rate of apoptosis and the expression of apoptosis marker proteins Caspase-3 and Caspase-9 were increased ( P<0.01). Also, the number of invasion cell and the expression of invasion marker proteins VEGF and MMP-14 were reduced in the three groups that treated with DDP ( P<0.01). Among the three groups of DDP-treated cells, the changes in sh- CCAT2 transfected cells was the most obvious ( P<0.01). Compared with the control group, the tumor volume of the three DDP treatment groups was smaller and the differences were statistically significant at 30 d ( P<0.01). The expression of CCAT2 mRNA was decreased in tumor tissues ( P<0.01), while apoptosis increased ( P<0.01). Among the three DDP treatment groups, the A549/DDP cell group transfected with sh- CCAT2 showed the most notable changes ( P<0.01). CONCLUSION: sh- CCAT2 can inhibit the proliferation of A549/DDP cells, induce apoptosis and reduce the cell invasion ability, thereby inhibiting the growth of A549/DDP cells.

Apatinib for salvage treatment of advanced malignant pleural mesothelioma: A case report.

RATIONALE: Malignant Pleural Mesothelioma (MPM) is rare cancer and has a poor prognosis with resistance to chemotherapy or radiotherapy. Until now there is no standard third-line treatment for patients who have failed second-line therapy. PATIENT CONCERNS: A 58-year-old non-smoking female peasant of ethnic Han was admitted to the oncology department of the 363 Hospital with a primary complaint of chest tightness and breathlessness from 3 months ago. DIAGNOSES: Positron emission tomography-computed tomography (PET/CT) examination showed "dirty" pleural and parietal pleural involvement as well as mediastinal and pulmonary hilar lymph node enlargement. Finally, cancer cells were seen after repeated pleural effusion cell examination. Immunohistochemistry confirmed epithelioid of pleural mesothelioma. INTERVENTIONS: Apatinib as a third-line treatment after failure from pemetrexed/cisplatin (PC) as the first-line chemotherapy and gemcitabine/cisplatin (GP) as the second-line chemotherapy. At first, 250 mg/day was given and 1 week later, the dose was increased to 500 mg/day. OUTCOMES: A 5-month progression-free survival was achieved and toxicity included severe hand-foot syndrome, mild proteinuria, and hypertension. LESSONS: Apatinib may be a potential therapeutic drug for MPM, particularly as a third-line treatment in cases resistant to chemotherapeutic options.

STARD13 is positively correlated with good prognosis and enhances 5-FU sensitivity via suppressing cancer stemness in hepatocellular carcinoma cells.

BACKGROUND: STARD13 has been revealed to suppress tumor progression. However, the roles in regulating the stemness of hepatocellular carcinoma (HCC) cells are unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect STARD13 expression in HCC tissues and normal adjacent tissues. Kaplan Meier (KM)-plotter analysis was performed to analyze the correlation between STARD13 expression and overall survival of HCC patients. Cell spheroid formation and ALDH1 activity analysis were carried out to detect the effects of STARD13 on the stemness of HCC cells. Furthermore, immunofluorescent, luciferase reporter, RhoA GTPase and F-actin visualization assays were performed to explore the mechanisms contributing to STARD13-mediated effects. RESULTS: STARD13 expression was significantly downregulated in HCC tissues compared with normal adjacent tissues, and was positively correlated with the overall survival of HCC patients. Functionally, overexpression of STARD13 inhibited cells stemness and enhanced 5-FU sensitivity in HCC cells. Mechanistically, STRAD13 overexpression suppressed RhoGTPase signaling and thus inhibited transcriptional factor YAP translocation from nuclear to cytoplasm, leading to the downregulation of transcriptional activity of YAP. Notably, the inhibitory effects of STARD13 on HCC cells stemness and 5-FU sensitivity were rescued by RhoA or YAP-5SA overexpression. CONCLUSION: Our results indicate that STARD13 could enhances 5-FU sensitivity by suppressing cancer stemness in hepatocellular carcinoma cells via attenuating YAP transcriptional activity.

Potential diagnostic value of serum p53 antibody for detecting colorectal cancer: A meta-analysis.

Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS). The result of pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were analyzed and compared with overall accuracy measures using diagnostic odds ratios (DORs) and area under the curve (AUC) analysis. Publication bias and heterogeneity were also assessed. A total of 11 trials that enrolled a combined 3,392 participants were included in the meta-analysis. Approximately 72.73% (8/11) of the included studies were of high quality (QUADAS score >7), and all were retrospective case-control studies. The pooled sensitivity was 0.19 [95% confidence interval (CI), 0.18-0.21] and pooled specificity was 0.93 (95% CI, 0.92-0.94). Results also demonstrated a PLR of 4.56 (95% CI, 3.27-6.34), NLR of 0.78 (95% CI, 0.71-0.85) and DOR of 6.70 (95% CI, 4.59-9.76). The symmetrical summary receiver operating characteristic curve was 0.73. Furthermore, no evidence of publication bias or heterogeneity was observed in the meta-analysis. Meta-analysis data indicated that s-p53 antibody possesses potential diagnostic value for CRC. However, discrimination power was somewhat limited due to the low sensitivity.