Targeting H19 by lentivirus-mediated RNA interference increases A549 cell migration and invasion.

BACKGROUND: Lung cancer is one of the most common and a lethal malignancy in the world and non-small cell lung cancer (NSCLC) is the most usual type. H19 long non-coding RNA (lncRNA) plays essential roles in tumor development. But its role in tumor metastasis is still unclear. MATERIALS AND METHODS: MACC1 RNAi and Lentivirus-mediated H19-specific shRNA was used to establish H19 stable knocking-down A549 cells. Transwell assays were performed to examine the effect of H19 knocking-down on A549 cells migration and invasion. The downstream signaling proteins targeted by H19 were also examined by western blot. AG1478 and U0126 were used as the inhibitor of EGFR and ERK1/2, respectively. RESULTS: The knockdown of H19 increased the migration and invasion of A549 cells, and knockdown of metastasis-associated in colon cancer 1 (MACC1) decreased the migration and invasion of A549 cells. Furthermore, MACC1 protein targeted by H19 was upregulated as well as the downstream signaling proteins including epidermal growth factor receptor (EGFR), ß-catenin, extracellular-signal-regulated kinase 1/2 (ERK1/2). Inhibited the expression of EGFR or ERK1/2 significantly decreased the migration and invasion of tumor cells. CONCLUSION: Our findings showed that H19 functions as a suppressor of NSCLC and plays an important role in the migration and invasion of NSCLC. More importantly, H19 may regulate NSCLC metastasis through modulating cellular signaling pathway proteins related to cell proliferation and cell adhesion, including MACC1, EGFR, ß-catenin and ERK1/2. These results put forward our understanding of the detailed mechanism of H19 lncRNA regulating the process of NSCLC metastasis.

Efficacy, Safety, and Health-Related Quality of Life With Camrelizumab Plus Pemetrexed and Carboplatin as First-Line Treatment for Advanced Nonsquamous NSCLC With Brain Metastases (CAP-BRAIN): A Multicenter, Open-Label, Single-Arm, Phase 2 Study.

INTRODUCTION: Systemic treatment options for NSCLC with brain metastases (BMs) are scarce. We evaluated the activity and safety of camrelizumab plus chemotherapy as first-line therapy in patients with advanced nonsquamous NSCLC with BMs. METHODS: This was a multicenter, single-arm, phase 2 trial (NCT04211090) conducted at seven hospitals in China. Eligible patients had treatment-naive metastatic nonsquamous NSCLC and BMs that were asymptomatic or symptoms controlled with dehydration therapy and no previous systemic treatment or local therapy for the target brain lesion. Patients received camrelizumab (200 mg) plus pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) intravenously on day 1 of each 21-day cycle for four cycles, followed by maintenance with camrelizumab (200 mg) and pemetrexed (500 mg/m2) every 21 days until disease progression, unacceptable toxicity, or death. The primary end point was confirmed intracranial objective response rate according to modified Response Evaluation Criteria in Solid Tumors version 1.1, which was primarily analyzed in the efficacy analysis set (EAS). RESULTS: A total of 45 patients were enrolled and treated (full analysis set), with 40 patients having at least one post-baseline tumor assessment (EAS). As of August 30, 2022, median follow-up duration was 12.5 months (95% confidence interval [CI]: 9.2-17.3). The confirmed intracranial objective response rate was 52.5% (95% CI: 36.1-68.5) in EAS and 46.7% (95% CI: 31.7-62.1) in full analysis set. The extracranial objective response rate was 47.5% (95% CI: 31.5-63.9) and 42.2% (95% CI: 27.7-57.8), respectively. Median intracranial progression-free survival was 7.6 months (95% CI: 4.6-not reached [NR]), median overall progression-free survival was 7.4 months (95% CI: 4.4-NR), and median overall survival was 21.0 months (95% CI: 15.9-NR). The most common treatment-related adverse events of grade 3 or higher were neutrophil count decrease (six [13.3%]) and anemia (four [8.9%]). One treatment-related death occurred owing to immune-related pneumonia. Linear mixed-effects model displayed that a positive trend for improvement in cognitive function and quality of life was observed based on Montreal Cognitive Assessment and Functional Assessment of Cancer Therapy-Lung scores (p = 0.025, p < 0.001). CONCLUSIONS: Camrelizumab plus pemetrexed and carboplatin was found to have an activity with manageable toxicity and to improve cognitive function and quality of life for patients with nonsquamous NSCLC with BMs in the first-line setting.

Preliminary Clinical Validation of a Filtration-Based CTC Assay for Tumor Burden and HER2 Status Monitoring in Metastatic Breast Cancer.

BACKGROUND: Bearing multidimensional tumor-relevant information ranging from genomic alterations to proteomic makeup, circulating tumor cells (CTCs) constitute a promising material for liquid biopsy. The clinical validity of CTCs has been most extensively studied in metastatic breast cancer (MBC). The Cellsearch assay is currently the most widely used, while alternative strategies are pursued. A filtration-based microfluidic device has been described for CTC enrichment, but its clinical relevance remains unknown. METHODS: In this preliminary study, we prospectively enrolled 47 MBC patients and evaluated the performance of the abovementioned CTC assay for tumor burden monitoring and human epidermal growth factor receptor 2 (HER2) status determination. RESULTS: At baseline, 51.1% patients (24/47) were CTC positive. CTC count and positivity were also significantly higher in samples that accompanied poorer radiographic response evaluations. Serial blood draws suggested that CTC count enabled more accurate monitoring of tumor burden than serum markers carcinoembryonic antigen and cancer antigen 15-3. Also, in contrast to previous reports, CTC-HER2 status was moderately consistent with tumor-HER2 status. CTC-HER2 status assessment was further supported by HER2 copy number measurements in select samples. CONCLUSION: The preliminary results from this study suggest promise for the interrogated CDC assay in several aspects, including sensitive CTC detection, accurate disease status reflection, and HER2 status determination. More studies are warranted to validate these findings and further characterize the value of CTC assay.

The effectiveness and safety of the rapid titration strategy of background controlled-release oxycodone hydrochloride for patients with moderate-to-severe cancer pain: A retrospective cohort study.

Background: Oxycodone hydrochloride is a semisynthetic narcotic analgesic agent. This study aimed to explore optimal titration strategy of controlled-release (CR) oxycodone hydrochloride in patients with cancer pain. Methods: 258 patients, who used regular strong opioids (morphine and CR oxycodone hydrochloride) for cancer pain across 25 three grade class hospitals in China during January 15th 2017 to April 30th 2017, were retrospectively studied. The patients were divided into 4 groups according to treatment regimens titrated. The pain remission rate and numeric rating scale (NRS) of cancer pain was recorded at 0, 12, 24, 36, 48, 60, 72 h after opioid titration. The incidence of adverse events (AEs) with therapy were also observed. Results: 12 h after treatment, pain remission rate of Group B, C and D was significantly higher (P < 0.001) than Group A. For the complete remission rate, there were also significant differences among the four groups (P < 0.001). No significant difference was found among four groups for pain remission rate at 24, 72 h after treatment. Multiple comparison of NRS scores showed that the both Group B and C varied significantly with Group D (P = 0.028, P = 0.05, respectively), showing superior analgesic effect over Group D. AEs were significantly different among groups (P < 0.01), with the most frequent AEs in Group A, lowest in Group B. Conclusion: The rapid titration strategy of background CR oxycodone hydrochloride was effectiveness and safety in patients with moderate-to-severe cancer pain.

Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

[Primary central nervous system lymphoma--a report of 32 cases with literature review].

BACKGROUND & OBJECTIVE: The incidence of primary central nervous system lymphoma (PCNSL) is increasing, and its prognosis is poor. This study was to investigate the clinical features of PCNSL, and evaluate the efficacy of high-dose methotrexate (MTX)-based chemotherapy for immunocompetent Chinese patients with PCNSL. METHODS: Clinical data of 32 patients (median age, 50 years) with pathologically confirmed PCNSL were analyzed retrospectively. Before Nov. 2001, CHOP with or without whole brain radiotherapy (WBRT) was employed; after then, high-dose MTX-based chemotherapy with or without WBRT was employed. RESULTS: Of the 32 PCNSL patients, 25 (78.1%) were more than 45 years old; 24 (75.0%) suffered intracranial hypertension; 25 (78.1%) had single intracranial mass; no positive case of cerebrospinal fluid (CSF) cellular examination was found; 28 (87.5%) were B-cell lymphoma, among which 19 (59.4%) were diffuse large B-cell lymphoma. Median follow-up of the patients was 13.5 months (1-84 months). Kaplan-Meier test showed that the median overall survival time was 26 months, and the 2-year survival rate was 45.7%. The complete response rate of the 18 patients who received high-dose MTX-based chemotherapy plus WBRT was 61.1%, the median survival time was more than 26 months, and the 2-year survival rate was 65.1%. The efficacy of high-dose MTX-based chemotherapy plus WBRT was better than that of CHOP plus WBRT. Log-rank test showed that the survival time of the patients with performance status (PS) of 0-1 or normal serum lactate dehydrogenase (LDH) was longer than those with PS of 2-3 or elevated LDH. CONCLUSIONS: PCNSL often occurs in middle-aged and aged patients, with intracranial hypertension as the main clinical manifestation. B-cell lymphoma is the predominant subtype. High-dose MTX-based chemotherapy plus WBRT is efficient and feasible for PCNSL.