A Meta-Analysis of the Effectiveness of Kanglaite Injection Plus First-Line EGFRTKIs Versus First-Line EGFRTKIs Alone Stage IIIB Lung Adenocarcinoma
David Kayembe Mwimbi,
Zhang Gaochenxi,
Wenpei Zhu,
Ying Wang,
Liang Yi,
Wang Dan,
Chen Huihui,
Shu Qijin
Issue:
Volume 5, Issue 3, September 2020
Pages:
43-55
Received:
27 February 2020
Accepted:
12 March 2020
Published:
23 July 2020
Abstract: Objective: Several systematic reviews for Therapeutic Effect of Kanglaite Injection Plus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Versus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Alone In Stage IIIB Advanced Lung Adenocarcinoma have recently emerged evidence. However, limited data are available regarding the activity of available EGFR TKIs against uncommon EGFR mutations. This meta-analysis evaluates the efficacy of Kanglaite Injection Plus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Versus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Alone In Stage IIIB Advanced Lung Adenocarcinoma. So therefore, Lung Adenocarcinoma related diseases have a profound economic impact on health care systems global wide, thus Kanglaite Injection combined with First-Line EGFR –TKIs have been shown to have beneficial effects than treatment with First-Line EGFR Tyrosine Kinase Inhibitors (TKIs) Alone. Methods: We electronically searched the literature of the China National Knowledge Infrastructure (Chinese language, English 2010-2019), Pub Med, Cochrane Central Register of Controlled Trails from database inception, CNKI, web of science Wang Fang, and manually searched Chinese-language oncology journals to identify randomized controlled trials (RCTs) of Kanglaite Injection Plus First Line EGFR-TKIs Versus First Line EGFR- TKIs Alone, regardless of their having been published or not, blinding, duration of treatment, or duration of follow-up. The quality of the included trials was assessed using the method recommended by The Cochrane Collaboration (CC). If heterogeneity existed among subgroups, then overall results (OS) were calculated based on a random-effects model; otherwise, a fixed effects model was used. Results: Electronic database searches yielded 1780 citations with NSCLC. Articles or Records Excluded by screening of the title/abstract level total 510, Records which are not Rcts 430, Study with no EGFR mutation analysis 590, Due to duplicated publication 180. Finally, we identified full text articles retrieved for detailled evaluation 70. The sample size of each trial had calculated by Rev Man 5.3. Pooled analyses performed using both fixed- and random-effects models revealed that compared with First Line of Egfr-Tkis alone, KLT injection plus First Line of Egfr-Tkis improved the response rate (relative risk [RR}, 1.34; 95% CI, 1.19-1.51 and RR, 1.35; 95% CI, 1.2 0-1.51, respectively). KLT injection plus First Line of Egfr-Tkis was associated with improvement in the symptoms of cough, dyspnea, chest pain, fatigue, and anorexia.
Abstract: Objective: Several systematic reviews for Therapeutic Effect of Kanglaite Injection Plus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Versus First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Alone In Stage IIIB Advanced Lung Adenocarcinoma have recently emerged evidence. How...
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Novel Targets of Protoporphyrin-IX Determined By Gene Expression Analysis
Yiyang Dai,
Wolfgang Kemmner
Issue:
Volume 5, Issue 3, September 2020
Pages:
56-64
Received:
8 July 2020
Accepted:
27 July 2020
Published:
18 August 2020
Abstract: Treatment with 5-Aminolevulinic acid-mediated photody¬namic therapy is a promising therapeutic option for various carcinomas. An appropriate photosensitizer for photody¬namic therapy is protoporphyrin-IX (PpIX), a light sensitive metabolite of heme synthesis. Incorporation of iron into PpIX leading to heme is carried out by Ferrochelatase (FECH). Earlier, we described a significant down regulation of FECH mRNA-expression and enzyme activity in carcinoma cells leading to an endogenous accumulation of PpIX. How PpIX affects the cell metabolism has not been examined so far. Thus, we tried to identify novel targets of PpIX with regard to cell proliferation, apoptosis and invasion. Endogenous generation of PpIX was induced by silencing of FECH in breast carcinoma MDA-MB-231 cells using a specific siRNA. Successful silencing of FECH was confirmed by RT-PCR and induction of PpIX was assessed by flow cytometry for each experiment. Subsequently, gene expression was determined using Affymetrix GeneChip® Human Gene 1.0 ST. Validation of microarray data was achieved by quantitative RT-PCR. Expression of one of the newly discovered target genes, BAMBI, was assessed by immunohistochemistry. In addition, the effect of silencing of FECH was examined by functional studies of cell apoptosis, invasion and wound healing. According to the gene expression analysis, an enhancement of PpIX suppressed Hedgehog as well as TGF-beta signaling. Expression of HHIP, a negative regulator of the hedgehog pathway, was found to be strongly increased after silencing of FECH. With regard to TGF-beta signaling, expression of the signaling inhibitor SMAD7 was strongly upregulated while the positive mediators SMAD2 and SMAD4 were less expressed after silencing FECH. Similarly, apoptosis of tumor cells was promoted, probably due to an increased expression of the pro-apoptotic gene APAF1 and a reduced expression of anti-apoptotic protein API5. Moreover, a significantly reduced invasion capability after treatment of cells with FECH siRNA was found. Here, we report that an accumulation of PpIX due to silencing of FECH affects various pathways and promotes apoptosis of tumor cells in different ways. Thus, silencing of FECH might have a tumor-suppressive effect. The search for substances which block FECH activity in a direct way therefore might be of high relevance for future cancer therapy approaches.
Abstract: Treatment with 5-Aminolevulinic acid-mediated photody¬namic therapy is a promising therapeutic option for various carcinomas. An appropriate photosensitizer for photody¬namic therapy is protoporphyrin-IX (PpIX), a light sensitive metabolite of heme synthesis. Incorporation of iron into PpIX leading to heme is carried out by Ferrochelatase (FECH). E...
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Clinical Results of Radiotherapy That Targeted for Tumor Thrombi from Hepatocellular Carcinoma: A Multicenter Retrospective Study
Takuya Nagano,
Akihiko Hoshi,
Masayuki Kurosaki,
Kazuma Sasamura,
Kaoru Tsuchiya,
Kazuma Toda,
Hirofumi Kuwabara,
Meika Namba,
Daigoro Matsubara,
Sayako Oota,
Yasuo Yoshioka,
Ryoichi Yoshimura,
Namiki Izumi
Issue:
Volume 5, Issue 3, September 2020
Pages:
65-77
Received:
16 September 2020
Accepted:
27 September 2020
Published:
7 October 2020
Abstract: Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively reviewed. We compared patient characteristics, overall survival (OS), the combined chemotherapy regimen, and objective response rates (ORRs) between the treatment modalities and analyzed cumulative incidence formula (CIF) for the deterioration in the Child-Pugh class and the progression of intrahepatic tumors. Results: We evaluated 64 patients, 39 of whom received combined chemotherapy with RT. Multivariate analysis showed that the Child-Pugh class, primary tumor size and the response of TT were significant prognostic factors for OS and the total equivalent dose in 2 Gy fractions (EQD2) of more than 48.75 Gy significantly contributed to ORRs (p=0.04). In the multivariate analysis of CIF, only acute liver damage was the significant factor for the deterioration in the Child-Pugh class (p=0.01) and the length of TT was significant for the progression of intrahepatic tumors (p=0.03). Conclusion: High doses should be delivered to TT, but long tumor thrombi are difficult to control. Tumor thrombus length is more important in predicting intrahepatic progression than the location of the tumor thrombus.
Abstract: Background: The aim of this multicenter study was to evaluate the outcome of radiotherapy (RT) that targeted for tumor thrombi (TT) from hepatocellular carcinoma (HCC), including the portal vein, hepatic vein, inferior vena cava, and bile duct TT. Methods: Patients who received RT for the treatment of TT between 2005 and 2020 were retrospectively r...
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