Intravenous Patient-Controlled Analgesia Versus Oral Opioid to Maintain Analgesia for Severe Cancer Pain: A Randomized Phase II Trial.

BACKGROUND: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. METHODS: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. RESULTS: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. CONCLUSIONS: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.

Knockdown of SETDB1 inhibits breast cancer progression by miR-381-3p-related regulation.

BACKGROUND: SET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer. Nevertheless, the molecular mechanism by which SETDB1 regulates breast cancer tumorigenesis is still unknown. METHODS: qRT-PCR assay or western blot analysis was performed to assess the expression level of SETDB1 mRNA or protein, respectively. siSETDB1, pCMV6-XL5-SETDB1, miR-381-3p mimic, or miR-381-3p inhibitor was transfected into cells to regulate the expression of SETDB1 or miR-381-3p. MiRNA directly interacted with SETDB1 was verified by luciferase reporter assay and RNA immunoprecipitation. CCK-8 assay, colony formation assay, flow cytometric analysis, and transwell assay were used to detect the abilities of cell proliferation, cell cycle progression and migration, respectively. Animal model of xenograft tumor was used to observe the regulatory effect of SETDB1 on tumor growth in vivo. RESULTS: We verified that SETDB1 mRNA level was upregulated in breast cancer tissues and cell lines, and SETDB1 depletion led to a suppression of cell proliferation, cell cycle progression and migration in vitro, as well as tumor growth in vivo. SETDB1 was verified to be a target of miR-381-3p. Moreover, miR-381-3p overexpression suppressed cell proliferation, cell cycle progression and migration, whereas SETDB1 abated miR-381-3p-mediated regulatory function on breast cancer cells. CONCLUSIONS: This study revealed that SETDB1 knockdown might suppress breast cancer progression at least partly by miR-381-3p-related regulation, providing a novel prospect in breast cancer therapy.

miR-17-92 cluster is connected with disease progression and oxaliplatin/capecitabine chemotherapy efficacy in advanced gastric cancer patients: A preliminary study.

This study aimed to determine the role of plasma miR-17-92 cluster level in predicting chemoresistance in patients with gastric cancer (GC) undergoing oxaliplatin/capecitabine (XELOX) chemotherapy.Patients recently diagnosed with advanced GC were chosen as participants based on the inclusion criteria. The plasma levels of miR-17-5p, miR-18a, miR-19a/b, miR-20a, and miR-92-1 (miR-17-92 cluster) were determined through quantitative RT-PCR of blood samples from GC patients and healthy volunteers. All the patients received XELOX chemotherapy, and the effectiveness of the chemotherapy was evaluated.The miR-17-92 plasma level was increased in advanced GC patients and decreased after XELOX chemotherapy. Moreover, the miR-17-92 cluster level was associated with chemotherapy response but not with chemotherapy-related toxicity. The miR-17-92 cluster plasma level was decreased in chemosensitive patients, but not in chemoresistant patients, after chemotherapy. The sensitivity and specificity of the combined detection of the miR-17-92 cluster in patients with advanced GC were 100% each.The results suggest that the miR-17-92 plasma level is associated with the progression of advanced GC and effectiveness of XELOX chemotherapy.

Knockdown of SETDB1 inhibits breast cancer progression by miR-381-3p-related regulation

BACKGROUND: SET domain bifurcated 1 (SETDB1) has been widely considered as an oncogene playing a critical role in many human cancers, including breast cancer. Nevertheless, the molecular mechanism by which SETDB1 regulates breast cancer tumorigenesis is still unknown. METHODS: qRT-PCR assay or western blot analysis was performed to assess the expression level of SETDB1 mRNA or protein, respectively. siSETDB1, pCMV6-XL5-SETDB1, miR-381-3p mimic, or miR-381-3p inhibitor was transfected into cells to regulate the expression of SETDB1 or miR-381-3p. MiRNA directly interacted with SETDB1 was verified by luciferase reporter assay and RNA immunoprecipitation. CCK-8 assay, colony formation assay, flow cytometric analysis, and transwell assay were used to detect the abilities of cell proliferation, cell cycle progression and migration, respectively. Animal model of xenograft tumor was used to observe the regulatory effect of SETDB1 on tumor growth in vivo. RESULTS: We verified that SETDB1 mRNA level was upregulated in breast cancer tissues and cell lines, and SETDB1 depletion led to a suppression of cell proliferation, cell cycle progression and migration in vitro, as well as tumor growth in vivo. SETDB1 was verified to be a target of miR-381-3p. Moreover, miR-381-3p overexpression suppressed cell proliferation, cell cycle progression and migration, whereas SETDB1 abated miR-381-3p-mediated regulatory function on breast cancer cells. CONCLUSIONS: This study revealed that SETDB1 knockdown might suppress breast cancer progression at least partly by miR-381-3p-related regulation, providing a novel prospect in breast cancer therapy.

Joint detection of ERCC1, TUBB3, and TYMS guidance selection of docetaxel, 5-fluorouracil and cisplatin (DDP) individual chemotherapy in advanced gastric cancer patients.

BACKGROUND: To investigate the guidance selection of docetaxel (D), cisplatin (DDP) (C), and 5-fluorouracil (5-FU) (F) as individual chemotherapy agents via joint detection of ERCC1, TUBB3, and TYMS genes in patients with advanced gastric cancer (AGC). METHOD: Clinical data of 120 patients with AGC who enrolled in our hospital between May 2009 and May 2012 were analyzed. These patients were randomly assigned to experimental and control groups. The mRNA expression of ERCC1, TUBB3, and TYMS was measured by DNA chip technology in the experimental group. Different chemotherapies were administered according to the mRNA expression levels of the three genes, while DCF chemotherapy was directly applied to the control group. Correlation between the three genes' mRNA levels, efficiency rate, the median time to progression (MTP), median survival time (MST) and adverse reactions was evaluated. RESULTS: As a result, there was a significant correlation between ERCC1 and TUBB3 mRNA expression (P = 0.005), but no obvious correlation between TUBB3 and TYMS or ERCC1 and TYMS. There was also no significant difference in the efficiency rate of chemotherapy (50% versus 55%; P = 0.357) and the MTP (10 months versus 7 months; P = 0.091) between the two groups. However, there was obvious significance in MST (13.7 months versus 11.6 months; P = 0.004). Additionally, the experimental group provided us with a more effective way for controlling adverse reactions to chemotherapy. CONCLUSION: Combination regimen of D, C, and F in AGC patients according to their ERCC1, TUBB3, and TYMS mRNA expression level may reduce adverse reactions and improve MST.

[Advances in hypoxia microenvironment and chemotherapy-resistant of lung cancer].

Lung cancer is one of the malignant tumors with highest incidence recently in our country. Tumor hypoxia phenomenon was first discovered in lung cancer. It plays important roles in tumor cell drug-resistance, apoptosis, invasion and metastasis, angiogenesis. Chemotherapy-resistant is one of the core reasons of treatment failure and disease progress, and many works on the study of chemotherapy-resistant have been done. This article reviewed the research progress of those mechanisms by which lung cancer hypoxia microenvironment could induce chemotherapy-resistance.