First-generation EGFR-TKI plus bevacizumab and chemotherapy for advanced EGFR-mutated non-squamous non-small-cell lung cancer: a retrospective study.

BACKGROUND: This study aimed to compare the efficacy and safety of different treatment modalities for previously untreated advanced EGFR-mutated non-squamous non-small-cell lung cancer (NSCLC). METHODS: This retrospective study included 196 advanced EGFR-mutated non-squamous NSCLC. 107 received EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy (T), 53 received EGFR-TKI + bevacizumab (T + A), and 36 received EGFR-TKI + bevacizumab + chemotherapy (T + A + C). The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: The median PFS was 27 months in the T + A + C group, 17 months in the T + A group, and 10 months in the T group. The multivariate analysis showed lower disease progression in the T + A + C group (HR, 0.377; 95% CI, 0.224-0.634; p < .001). Subgroup analysis showed that the T + A + C group did significantly improve PFS in patients with metastatic organs ≥2, brain metastases, liver metastases, and EGFR 19del compared to T + A group. No significant improvement in OS in the T + A + C group versus the T + A group, but a significant benefit in the subgroup of patients with metastatic organs ≥2. We also performed a subgroup analysis of the T + A + C group versus the T group, which similarly showed that the T + A + C group had better PFS than the T group in most subgroups, and the T + A + C group significantly improved OS in patients with metastatic organ ≥2 and liver metastases compared with the T group. The ORR was significantly higher in the T + A + C group than A + T and T groups (83.3% vs 71.7% vs 60.7%, p = .033). In safety, the T + A + C group had a higher incidence of AEs, but the majority was grade 1-2. The most frequent AEs of grade ≥ 3 were leukopenia (8.3%) and increased aminotransferase (8.3%) in the T + A + C group. CONCLUSIONS: First-generation EGFR-TKI plus bevacizumab plus chemotherapy was a promising strategy for advanced EGFR-mutated non-squamous NSCLC.

Silencing Rac1 and Prex1 Inhibit Epithelial-Mesenchymal Transition in Human Gastric Cancer Cells Induced by Transforming Growth Factor-ß1.

BACKGROUND/AIMS: Transforming growth factor-beta can influence tumor cells, causing epithelial-mesenchymal transition and enhancing their invasion and metastasis ability. Rac1 protein could be used as an independent tumor diagnostic marker and survival predictor. Prex1 is closely related to cell metastasis. In this study, the impact of silencing Rac1 and Prex1 on transforming growth factor-beta 1-induced epithelial-mesenchymal transition and apoptosis of human gastric cancer cells MGC-803 and MKN45 was investigated. MATERIALS AND METHODS: MGC-803 and MKN45 cells received recombinant transforming growth factor-beta 1 (rTGF-ß1) treatments at various concentrations. Cell Counting Kit-8 kit was used to determine cell viability. Rac1 and Prex1 interference vectors were transfected into the rTGF-ß1-treated MGC-803 and MKN45 cells. Cell apoptosis and migration were detected by flow cytometry and scratch test, respectively. Western blot was used to detect the epithelial-mesenchymal transition-related markers E-cadherin, N-cadherin, vimentin, and PDLIM2 expression levels. RESULTS: The rTGF-ß1 (10 ng/mL) could promote MGC-803 and MKN45 cell viability. Silencing Rac1 and Prex1 could increase E-cadherin and PDLIM2 expression, decrease N-cadherin and vimentin expression, inhibit cell viability and migration, and promote apoptosis in rTGF-ß1-treated MGC-803 and MKN45 cells. CONCLUSIONS: Silencing Rac1 and Prex1 could inhibit epithelial-mesenchymal transition, reduce cell viability and migration, and promote apoptosis in human gastric cancer cells.

Dual-energy computed tomography in reducing the effective radiation dose of computed tomography urography in patients with urinary calculi.

Background: To evaluate the diagnostic performance of split-bolus single-phase dual-energy computed tomography (DECT) with virtual non-contrast computed tomography (VNCT) compared to three-phase computed tomography (CT) urography in patients with urinary calculi, and to examine the performance of split-bolus single-phase DECT when reducing the effective dose. Methods: A total of 48 patients with abdominal pain or hematuria suggestive of unilateral urinary calculi were enrolled and randomly divided into the experimental and control groups, with 24 cases in each group. Patients in the experimental group underwent split-bolus single-phase DECT to obtain a mixed nephrographic excretory phase. Patients in the control group accepted a single-bolus three-phase CT urography scan (non-contrast, nephrographic phase, and excretory phase). The CT values and the contrast-to-noise ratio (CNR) of 7 segments of the urinary tract were measured and compared between the two groups by using the Mann-Whitney U test. The dose-length product (DLP) and effective dose of each patient were compared between the two groups using an independent t-test. Results: Among all 48 patients, 35 calculi were detected in the experimental group (n=24), and 47 calculi were detected in the control group (n=24). There was no significant difference between the two groups in both CT value measurements and the CNR. The mean DLP and mean effective dose of the experimental group were significantly lower than those of the control group, and the effective dose in the experimental group was decreased by 40% compared with the control group. Conclusions: The application of DECT combined with split-bolus nephrographic excretory phase CT urography can reveal the urinary calculi covered by a contrast medium and also reduce the effective dose exposure to patients.

Added value of computed tomography venography in the identification of abnormities in veins of lower extremities.

OBJECTIVE: To investigate the efficacy of direct computed tomography venography (CTV) in early and accurate detection of lower extremity venous (LEV) abnormalities. METHODS: Cross-sectional research was conducted in Hebei General Hospital of China. A total of 211 CTV reports of both lower extremities from January 2017 to September 2019, 75 color Doppler ultrasound (DUS) examinations, and eight intravascular angiography records of these patients over the same period were collected from the hospital. Comparisons were made for the reported number and percentage of LEV abnormalities (thrombosis, stenosis including severe stenosis, and varicosities). Chi-square test and t-test were applied to compare the rates and means, respectively. Significance level α was 0.05. Individual interviews were performed to understand the perceptions of medical staff and patients on the application of CTV, and the interview results were analyzed. RESULTS: Of the 75 cases with both CTV and DUS reports, 159 abnormalities occurring in the lower extremity deep veins (LEDV) were reported, among which 125 (79%) and 18 (11%) were reported by CTV and DUS on a single basis, respectively, whereas 16 (10%) were reported by CTV and DUS simultaneously. A statistically significant greater number of abnormalities in LEDV were identified by CTV than DUS in both males and females (χ2males = 78.449, χ2females = 27.574, χ2total = 104.164, p < .05). In the 211 CTV reports, among the 383 abnormalities reported in total, the common iliac vein (CIV) had the highest number of reported abnormalities (132, 34.5%), followed by the femoral vein (93, 24.3%). The ratios between LEDV abnormality and patient numbers were 1.055 and 0.688 for left and right sides in males, and 0.892 and 0.461 for left and right sides in females, respectively, with that for the left side statistically significantly higher than the right one (tmale = 2.896, tfemale = 4.347, p < .05). The incidence of thrombosis was 10.9% (95% CI = 6.7 ∼ 15.1%). Reported abnormities in CIV by CTV were in agreement with those by intravascular angiography. The medical staff believed that CTV could guide the performance of surgeries for LEV and the patients perceived CTV acceptable. CONCLUSIONS: Application of CTV for early and accurate detection of LEDV abnormalities including thrombosis has been proven to be efficient. Corresponding benefit in early intervention and reduction of severe complications of such abnormalities is of important value. CTV earned good recognition from medical staff and patients. Hence, it could be considered as part of global health assistance cooperation with developing countries to facilitate enhanced medical services.

Non-contrast-enhanced magnetic resonance imaging technique diagnoses DVT and classifies thrombus.

The accuracy of non-contrast MRI in diagnosing acute deep vein thrombosis (DVT) of the lower extremities is different. To explore the application of high-resolution non-contrast 3D CUBE T1-weighted MRI in the lower extremities DVT. We recruited 26 patients suspected DVT of the lower extremities from Hebei General Hospital in China. All patients underwent high-resolution non-contrast 3D CUBE T1-weighted MRI. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of diagnosing thrombosis. And we divided thrombi into two parts: filling thrombus (FT) and non-filling thrombus (NFT), compared the agreement between MRI and Ultrasound (US) and analysed the locations of thrombi. Compared with US, MRI yielded a sensitivity of 79%, a specificity of 94.2% in mean value, a sensitivity of 85.7%, 97.4%, and 51.7% in iliac, femoral-popliteal, and calf segments respectively, a specificity of 97.6%, 88.3%, and 98.2% in iliac, femoral-popliteal, and in calf segments respectively. The accuracy of MRI in the diagnosis of lower extremity DVT was in very good agreement (κ = 0.711, 95% CI 0.627, 0.795). The FT was the most part in US and CUBE (68/56), CUBE can detect more NFT in femoral vein than US (22/4). 3D CUBE T1-weighted MRI can be used to accurately diagnose acute DVT and detect more NFT. It has the potential of follow-up at the end of treatment to establish a new baseline to stop anticoagulant drug.

Combined high-resolution 3D CUBE T1-weighted imaging and non-contrast-enhanced magnetic resonance venography for evaluation of vein stenosis in May-Thurner syndrome.

PURPOSE: To explore the feasibility of high-resolution MRI 3-dimensional (3D) CUBE T1-weighted magnetic resonance imaging (MRI) in combination with non-contrast-enhanced (NCE) magnetic resonance venography (MRV) for the assessment of lumen stenosis in May-Thurner syndrome. METHODS: Twenty-nine patients underwent computed tomography venography (CTV) and high-resolution MRI-CUBE T1, and NCE MRV acquisitions. ANOVA and LSD tests were used to compare the stenosis rate and narrowest and distal diameters of the vessel lumen. RESULTS: There were no significant differences in the estimated stenosis rate between CTV, CUBE T1, and NCE MRV (p = 0.768). However, there were significant differences in the measured stenosis diameters of the left common iliac vein (LCIV), with CTV giving the largest mean diameter and CUBE had the smallest mean diameter (p < 0.05). The measured normal LCIV diameters did not significantly differ between MRV and CUBE (p = 0.075) but were significantly larger on CTV than on MRV and CUBE (p < 0.05). CONCLUSIONS: Compared with CTV, a combination of CUBE and MRV could provide an improved assessment of the degree of lumen stenosis in May-Thurner syndrome and demonstrate acute thrombosis. MRI underestimates the diameter of the vessel in comparison with CTV. MRI can be a substitute tool for Duplex ultrasound and CTV.

LINC00200 contributes to the chemoresistance to oxaliplatin of gastric cancer cells via regulating E2F1/RAD51 axis.

The goal of this research was to decipher the biological functions and mechanism of long intergenic non-protein coding RNA 200 (LINC00200) in gastric cancer (GC). In this study, our data confirmed that LINC00200 expression was up-regulated in GC tissues and its high expression was correlated with the poor differentiation of GC tissues and lymph node metastasis of the patients. In vitro experiments indicated that, the overexpression of LINC00200 facilitated the proliferation of GC cells, constrained their apoptosis, and increased the IC50 of oxaliplatin (Oxa), whereas knockdown of LINC00200 exhibited the opposite effects. Additionally, we demonstrated that LINC00200 could bind to E2F transcription factor 1 (E2F1), and the up-regulation of LINC00200 expression enhanced the binding between E2F1 and RAD51 promoter, hence promoting RAD51 transcription, while knockdown of LINC00200 inhibited the transcription of RAD51. In conclusion, LINC00200 may recruit E2F1 to the RAD51 recombinase (RAD51) promoter region, thereby up-regulating the expression of RAD51 and enhancing the chemoresistance of GC cells to Oxa. Our data suggested that LINC00200 could probably be a promising target for treating GC.

AT-rich interactive domain1A determines sensitivity to oxaliplatin in gastric cancer cells.

BACKGROUND: Gastric cancer is a highly heterogeneous disease and its traditional histopathological classification is difficult to meet clinical needs. Oxaliplatin is an antitumor drug with high efficiency and low toxicity. Therefore, the insensitivity or secondary drug resistance of oxaliplatin to gastric cancer is vital for tumor progression. The aim of this study was to investigate the sensitivity of gastric cancer cells to oxaliplatin after ARID1A (AT-rich interactive domain1A gene) gene silencing. METHODS: MGC-803 and AGS cells were selected as gastric cancer cells for study. ARID1A protein and mRNA expression was detected by Western blot and quantitative reverse-transcription PCR (qRT-PCR). The short hairpin RNA (shRNA) fragment of ARID1A gene silencing was constructed and introduced into gastric cancer cells. The cell proliferation activity was calculated using CCK8 and the IC50 was calculated. The flow cytometry was used to detect the cell cycle and apoptosis rate. The ability of cell invasion was detected by transwell method. Cells were treated with different concentrations of oxaliplatin. RESULTS: The proliferation of gastric cancer cells was promoted by ARID1A gene silencing (P<0.01), the quantity of cells in S phase increased (P<0.05), and the invasive ability increased (P<0.05). After treatment with oxaliplatin at different concentrations, ARID1A gene silencing reduced the inhibition rate of oxaliplatin on gastric cancer cells and apoptosis rate (P<0.05), and increased IC 50 (P<0.01). CONCLUSIONS: ARID1A gene silencing, a factor promoting proliferation of gastric cancer cells, would reduce the sensitivity of gastric cancer cells to oxaliplatin, which can provide a basis for the exploration of targeted drugs for individualized treatment of gastric cancer.

Paclitaxel, 5-fluorouracil, and leucovorin combination chemotherapy as first-line treatment in patients with advanced gastric cancer.

The aim of this retrospective analysis was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, 5-fluorouracil, and leucovorin (TFL) as first-line treatment in patients with advanced gastric cancer (AGC). One hundred and thirteen patients were enrolled in the study who were confirmed to have AGC by histopathology. These patients were treated with TFL: paclitaxel at a dose of 135 mg/m as a 3-h intravenous infusion on day 1, LV 400 mg/m as an intravenous infusion over 2 h on day 1, followed by 5-fluorouracil 2400 mg/m as an infusion over a 46-h period on 3 consecutive days. Cycles were repeated every 2 weeks. A total of 113 patients were assessed for their response to therapy. A total of three patients achieved complete responses and 46 patients achieved partial responses, yielding an overall objective response rate of 43.4% [95% confidence interval (CI): 34.3-52.5%]. Fifty-four cases of stable disease and 10 cases of progressive disease were observed in the remaining patients. The median time to progression and overall survival were 5.2 months (95% CI: 4.7-5.8 months) and 14.1 months (95% CI: 12.5-15.8 months), respectively. Toxicities were tolerable and moderate. The most common grade 3-4 toxicities included leukopenia (16.8%), neutropenia (17.7%), anemia (8.0%), thrombocytopenia (5.3%), and fatigue (6.2%). Combination chemotherapy with TFL offers an active and safe therapeutic approach for patients with AGC.

Combination chemotherapy with paclitaxel and oxaliplatin as first-line treatment in patients with advanced gastric cancer.

PURPOSE: This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with Paclitaxel (PTX) and Oxaliplatin (OXA) as first-line treatment for patients with advanced gastric cancer (AGC). METHODS: One hundred and seven patients with locally advanced or metastatic gastric adenocarcinoma received intravenous infusions of PTX at 135 mg/m2 and OXA at 85 mg/m2 on day 1 every 14 days. RESULTS: Among 107 patients enrolled, 9 patients could not be evaluated for a response because of the absence of any measurable lesions. Assessment of the response of 98 patients was made. The overall objective response rate was 42.9% (95% CI 32.9-52.8%), with two complete responses and 40 partial responses. The disease control was 79.6% (95% CI 71.5-87.7%). With 29 months of the median time of follow-up, the median progression-free survival was 5.8 months (95% CI 4.30-7.30 months) and the median overall survival was 11.5 months (95% CI 9.08-13.9 months). The 1-year survival rate was 48.0%. The most common grades 3 and 4 toxicities included neutropenia (32.7%), leucopenia (17.8%), fatigue (5.61%), and anemia (4.67%). Peripheral neuropathy occurred in 23.4% patients and grade 2 or higher peripheral neuropathy occurred in 12.1% of the patients. CONCLUSIONS: Combination chemotherapy with PTX and OXA offers a new, effective and safe regimen for patients with advanced gastric cancer.

Paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in patients with recurrent or metastatic gastric cancer.

PURPOSE: This study evaluated the efficacy and toxicity of combination chemotherapy with paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin (POFL) in patients with recurrent or metastatic gastric cancer. METHODS: One hundred and thirty-eight patients with histologically confirmed recurrent or metastatic gastric adenocarcinoma were treated with the POFL regimen: paclitaxel at a dose of 135 mg/m2 as a 3-hour intravenous infusion on day 1, oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 as an intravenous infusion over 2 hours on day 1, followed by 5-fluorouracil 2,400 mg/m2 as an infusion over a 46-hour period on 3 consecutive days, in a 2-week cycle. RESULTS: Twelve patients could not be evaluated for response because of the absence of any measurable lesions or early discontinuation of therapy, so responses were assessed in 126 patients. The overall objective response rate was 56.3% (95% CI, 47.5%-64.9%). The median time to progression was 6.7 months (95% CI, 5.8-7.6 months), and the median overall survival was 12.6 months (95% CI, 11.3-13.9 months). The most common grade 3 and 4 toxicities were neutropenia (50.7%), peripheral neurotoxicity (16.7%) and alopecia (27.5%). CONCLUSIONS: Combination chemotherapy with POFL offers a new, active and safe approach to the treatment of recurrent or metastatic gastric cancer.

Combination Chemotherapy with S-1 and Oxaliplatin (SOX) as First-Line Treatment in Elderly Patients with Advanced Gastric Cancer.

This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m(2) oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3-63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8-87.8 %). The median follow-up period was 23 months (range, 5-42 months). The median time to progression was 6.9 months (95 %CI, 5.5-8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4-14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7-66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and well-tolerated regimen for elderly patients with advanced gastric cancer.