Characterization and cytocompatibility of thermosensitive hydrogel embedded with chitosan nanoparticles for delivery of bone morphogenetic protein-2 plasmid DNA.

A novel injectable chitosan thermosensitive hydrogel was designed as a target multi-effect scaffold for endogenous repair of the periodontium. The hydrogel complex was designed by embedding chitosan nanoparticles (CSn) loaded with bone morphogenetic protein-2 plasmid DNA (pDNA-BMP2) into a chitosan (CS)-based hydrogel with α,ß-glycerophosphate (α,ß-GP), termed CS/CSn(pDNA-BMP2)-GP. Characterization, the in vitro release profile for pDNA-BMP2, and cytocompatibility to human periodontal ligament cells (HPDLCs), were then conducted. The average diameter of the CSn(pDNA-BMP2) was 270.1 nm with a polydispersity index (PDI) of 0.486 and zeta potential of +27.0 mv. A DNase I protection assay showed that CSn could protect the pDNA-BMP2 from nuclease degradation. Encapsulation efficiency and loading capacity of CSn(pDNA-BMP2) were more than 80 and 30 %, respectively. The sol-gel transition time was only 3 min when CSn(pDNA-BMP2) was added into the CS/α,ß-GP system. Scanning electron microscopy showed that CSn(pDNA-BMP2) was randomly dispersed in a network with regular holes and a porous structure. Weighting method showed the swelling ratio and degradation was faster in medium of pH 4.0 than pH 6.8. An in vitro pDNA-BMP2 release test showed that the cumulative release rate of pDNA-BMP2 was much slower from CS/CSn-GP than from CSn in identical release media. In release media with different pH, pDNA-BMP2 release was much slower at pH 6.8 than at pH 4.0. Three-dimensional culture with HPDLCs showed good cell proliferation and the Cell-Counting Kit-8 assay indicated improved cell growth with the addition of CSn(pDNA-BMP2) to CS/α,ß-GP. In summary, the CS/CSn(pDNA-BMP2)-GP complex system exhibited excellent biological properties and cytocompatibility, indicating great potential as a gene delivery carrier and tissue regeneration scaffold for endogenous repair of the periodontium.

[Effect of integrated Chinese medical treatment (as maintenance therapy) on the survival time of patients with advanced non-small-cell lung cancer: a clinical study].

OBJECTIVE: To observe clinical effect of integrated Chinese medical (CM) treatment (as maintenance therapy) on the progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) after first-line chemotherapy. METHODS: The study was a prospective, randomized, controlled clinical trial. Totally 69 non-progressive advanced NSCLC patients treated with first-line chemotherapy were randomly assigned to the test group (34 cases) and the control group (35 cases). Patients in the control group were treated with one Western drug chemotherapy (Gemcitabine or Alimta or docetaxel). Those in the test group were treated with integrated CM treatment (CM decoction, CM Intravenous preparation, and point application). Each cycle consisted of 21 days. Treatment lasted till the disease progressed, or intolerable toxic/adverse reactions occurred, or patients refused to continue the treatment. Patients' life spans were regularly followed-up. RESULTS: (1) The median cycle of maintenance therapy was 2 cycles for two groups with no statistical difference (P =0.274). The median PFS was 12.43 weeks in the test group and 10.00 weeks in the control group, showing statistical difference (P =0.025). The middle survival time (MST) was 18.8 months in the test group and 16.73 months in the control group, showing no statistical difference (P =0.437). CONCLUSION: CM treatment (as maintenance therapy) showed quail effect to one Western drug chemotherapy in prolonging patients' life span.

Oral Decoctions Based on Qi-Yin Syndrome Differentiation After Adjuvant Chemotherapy in Resected Stage ΙΙΙA Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

OBJECTIVE: Powerful adjuvant strategies are required to improve the survival of patients with completely resected stage ΙΙΙA non-small cell lung cancer (NSCLC). We aimed to compare the efficacy of traditional Chinese medicine (TCM) treatment versus observation after adjuvant chemotherapy in these patients. METHODS: Eligible patients were randomized 1:1 to receive either oral decoctions based on Qi-Yin syndrome differentiation (TCM group) or observation (observation group). The intervention lasted for 12 months. The primary endpoint was 1-year disease-free survival (DFS). Secondary endpoints were DFS, quality of life, regulatory T cells (Tregs), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on the surface of Tregs in peripheral blood. We used EORTC QLQ-LC43 to evaluate quality of life. RESULTS: Between Apr 29, 2019, and Nov 11, 2021, 75 patients were randomly assigned to oral decoctions based on Qi-Yin syndrome differentiation (n = 38) or observation (n = 37). The full analysis set included 35 patients in the TCM group and 35 in the observation group. After a median follow-up of 24.2 months, oral decoctions based on Qi-Yin syndrome differentiation improved DFS compared with observation (HR 0.378, 95% CI: 0.157-0.912; P = .03). One-year DFS was 82.1% in the TCM group and 61.9% in the observation group (P = .06). Three months after randomization, scores of total health, role function, emotional function, and social function in the TCM group were higher than those in the observation group (P < .01 for all), scores of fatigue, pain, insomnia, appetite loss, constipation, cough, and chest pain were lower than those in the observation group (P < .05 for all); there was no significant difference in the proportion of Tregs between the TCM group and the observation group (P = .58); the proportion of CTLA-4+Tregs in the TCM group was lower than that in the observation group (P = .046). There were no adverse events that occurred in both groups. CONCLUSIONS: Oral decoctions based on Qi-Yin syndrome differentiation after adjuvant chemotherapy prolonged DFS, reduced the risk of disease recurrence and metastasis, improved quality of life, and down-regulated the proportion of CTLA-4+Tregs in completely resected stage ΙΙΙA NSCLC patients. TRIAL REGISTRATION: Chinese Clinical Trial Register, No. ChiCTR1800019396. Date of registration: 9 November 2018.

Simultaneous development of pneumonitis and autoimmune diabetes secondary to immune checkpoint inhibitor treatment with durvalumab in an advanced small cell lung cancer patient: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed. PATIENT CONCERNS: In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab. DIAGNOSES: According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus. INTERVENTIONS: Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed. OUTCOMES: After the cessation of durvalumab and comprehensive treatment, the patient's respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy. LESSONS: With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients.

Mechanism underlying the effect of Liujunzi decoction on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy.

OBJECTIVE: To further clarify the anticancer mechanisms of Liujunzi decoction and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy. METHODS: The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein-protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software. RESULTS: A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine-cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development. CONCLUSIONS: One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.

[Effect of Chinese medicine comprehensive regimen as the maintenance therapy on time to progression and quality of life of patients with advanced non-small-cell lung cancer].

OBJECTIVE: To observe the effect of Chinese medicine (CM) comprehensive regimen as the maintenance therapy (MT) on time to progression (TTP) and quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). METHODS: The study was a prospective, randomized and controlled clinical trial. Fifty non-progressive patients with advanced NSCLC who responded to first-line therapy were randomized into the test group (25 cases, treated with CM comprehensive regimen: intravenous dripping of Chinese herbal preparation, oral administration of Chinese herbal decoction, and point application) and the control group [25 cases, treated with one of three single-agent maintenance chemotherapy regimens: pemetrexed (500 mg/m2, day 1), docetaxel (75 mg/m2, day 1), and gemcitabine (1000 mg/mi, day 1 and day 8) in the ratio of 1:1]. Each cycle consisted of 21 days. Cycles were repeated until the disease progressed, or intolerable toxic or adverse reaction occurred, or patients refused to continue the treatment. The primary end point was TTP and the secondary end point was QOL. QOL was evaluated using the European Organization for Research and Treatment of Cancer quality-of-life questionnaire QLQ-LC43 (EORTC QLQ-LC43). TTP of fifty patients and QOL of 43 patients had been statistically analyzed. RESULTS: (1) The TTP in the test group was prolonged for 23 days when compared with that of the control group, with insignificant difference (87 days vs 64 days, P=0.063). (2) The scores of domains in EORTC QLQ-LC43 were statistically significantly better in the test group than in the control group (P<0.05) except cognitive and social functions, the symptoms of dysphagia and pain in other parts. CONCLUSIONS: (1) The CM comprehensive regimen as MT had equivalent efficacy on TTP when compared with single-agent maintenance chemotherapy regimen. It was advantageous over improving the QOL. (2) It is necessary to enlarge the sample size to further confirm the therapeutic efficacy of CM comprehensive regimen as MT in treatment of patients with advanced NSCLC.

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases during Apical Periodontitis Development.

INTRODUCTION: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice. METHODS: AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. RESULTS: The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods. CONCLUSIONS: MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP.

Responses to crizotinib and cabozantinib in patient with lung adenocarcinoma harboring mesenchymal-epithelial transition factor exon 14 skipping mutation: A case report.

RATIONALE: Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. PATIENT CONCERNS: A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). DIAGNOSES: MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. INTERVENTIONS: Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. OUTCOMES: Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. LESSONS: As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.

[Regulatory effect of jianpi wenshen recipe in combining with chemotherapy on the blood level of estradiol in patients with lung cancer].

OBJECTIVE: To observe the regulatory effect of Jianpi Wenshen Recipe (JPWS), a Chinese herbal preparation for strengthening Pi and warming Shen, combined with chemotherapy on the level of estradiol (E2) in patients with mid-late non-small cell lung cancer (NSCLC), and to analyse the relationship between the changes of estradiol and tumor size. METHODS: Fifty-one NSCLC patients were randomized into three groups: 16 cases in the JPWS group treated with JPWS alone, 18 cases in the test group treated with combined therapy of JPWS plus chemotherapy, and 17 cases in the chemotherapy group treated with chemotherapy alone, all were treated for 2 months. The changes of blood E2 level and tumor size before and after treatment were compared. RESULTS: The disease control rate in the JPWS group and combined therapy group was 53.85% (7/13) and 80.00% (8/10), respectively, both were higher than that in the chemotherapy group (44.40%, 4/9), but the difference showed statistical insignificance (P > 0.05). E2 level was significantly lowered after treatment in the former two groups (all P < 0.05), and the change was in accordance with that of tumor size in 26 out of 31 patients (P < 0.01). CONCLUSION: JPWS combined with chemthherapy can stabilize the tumor size and down-regulate E2 levelo, with the change of E2 correlated with that of tumor size in patients. Hence, decreasing E2 is one of the mechanisms for JPWS in treating lung cancer.

TOB1-AS1 suppresses non-small cell lung cancer cell migration and invasion through a ceRNA network.

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-associated mortality. Recent studies revealed that long non-coding (lnc)RNAs have crucial roles in human cancers. The present study was the first, to the best of our knowledge, to indicate that the lncRNA transducer of ERBB2, 1-antisense 1 (TOB1-AS1) acts as a tumor suppressor in NSCLC. Knockdown of TOB1-AS1 significantly induced NSCLC cell migration, invasion and proliferation. It was also demonstrated that the higher expression of TOB1-AS1 in NSCLC samples was associated with longer overall survival time. Furthermore, a TOB1-AS1-mediated competing endogenous RNA network in NSCLC was constructed, including Homo sapiens (hsa)-microRNA (miR)-27a-3p, hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-27b-3p, hsa-miR-23c, dynein cytoplasmic 2 light intermediate chain 1, E4F transcription factor 1, TSPY-like 4, component of oligomeric Golgi complex 7, inositol hexakisphosphate kinase 2 and deltex E3 ubiquitin ligase 3. Of note, dysregulation of targets of TOB1-AS1 was associated with the prognosis of NSCLC patients. The present study suggested that TOB1-AS1 may serve as a novel biomarker for NSCLC.

Traditional Chinese Medicine Treatment as Adjuvant Therapy in Completely Resected Stage IB-IIIA Non-Small-Cell Lung Cancer: Study Protocol for a Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Adjuvant chemotherapy (AC) has been proven to yield an approximately 5% improvement in 5-year survival for patients with early-stage non-small-cell lung cancer. With such small gains in survival, the optimal treatment regimen remains to be established. Traditional Chinese medicine (TCM) treatment in combination with AC is frequently used in China. The efficacy and safety of this integrated approach should be scientifically evaluated. We present the rationale and study design of the Combined Adjuvant Chemotherapy and Traditional Chinese Medicine (ACTCM) trial (ChiCTR-IPR-16009062). The ACTCM trial, a prospective multicenter double-blind randomized placebo-controlled study, will recruit 312 patients overall from 5 clinical research centers in China. Within 6 weeks of the thoracic surgery, eligible participants with stages IB-IIIA non-small-cell lung cancer will be randomly assigned in a 1:1 ratio to either the treatment or control group. Patients in the treatment group will receive AC combined with TCM herbal treatment for 4 cycles, then TCM herbal plus injection treatment for 4 cycles. Patients in the control group will receive AC combined with TCM placebo for 4 cycles and then TCM placebo for 4 cycles. Treatment will be discontinued if disease progression or unacceptable toxicity occurs. The primary end point is 2-year disease-free survival. Secondary end points include disease-free survival and quality of life. Other end points are TCM symptoms, performance status, and safety of the regimens. Recruitment started in October 2016 and is ongoing.

[Clinical effect of yiqi yangyin jiedu decoction in treating patients with advanced non-small cell lung cancer].

OBJECTIVE: To observe the clinical therapeutic effect and mechanism of Yiqi Yangyin Jiedu Decoction (YYJD, a Chinese herbal recipe for strengthening qi, nourishing yin and removing toxic substance, consisting of milkvetch root 30 g, glehnia root 30 g, asparagus root 15 g, lilyturf root 15 g, grossy privet fruit 12 g, spikemoss herb 30 g, Chinese sage herb 30 g, manyleaf paris rhizome 30 g, etc. ) in treating patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Sixty patients with advanced lung cancer of qi-yin deficiency syndrome were randomized into three groups: the TCM group (A) treated with YYJD, the chemotherapy group (B) treated by chemotherapy with NP or GP protocol, and the combined treated group (C) treated with YYJD and chemotherapy in combination. The efficacy was evaluated after two cycles of treatment. RESULTS: The total effective rate for alleviating qi-yin deficiency syndrome in group A was 80%, significantly higher than that in Group C and B (35% and 20%, P <0.01) respectively. The KPS increasing and stabilizing rate in Group A and C was 90% and 85% respectively, significantly higher than that in Group B (75%), and difference between A and B was significant (P <0.05). In Group C after treatment, CD(3)+ showed a rising trend (P = 0.05), different to that in Group A and B (P <0.05 and P <0.01); CD(4)+ significantly increased (P <0.05) and CD(4)+/CD(8)+ ratio showed increasing trend (P = 0.06), while in Group B both were decreased significantly, showed significantly difference (P < 0.05). CD(8)+ CD(28)+ significantly increased after treatment in Group A and C (P <0.01 and P <0.05), but showed decreasing trend (P = 0.06) in Group B, significant difference was shown between B and C (P <0.05). CONCLUSION: YYJD can ameliorate the qi-yin deficiency syndrome evidently in advance lung cancer patients; improve their quality of life, the mechanism might be by way of enhancing T-lymphocyte activity and killer T-cell function, to elevate the T-cell mediated immunity in a round way.

Traditional Chinese Medicine treatment as maintenance therapy in advanced non-small-cell lung cancer: A randomized controlled trial.

OBJECTIVES: Maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC. METHODS: This study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20ml/d, d1-d10), herbal decoction (d1-d21) and Chinese acupoint application (d1-d21), n=32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500mg/m(2), d1), docetaxel (75mg/m(2), d1) or gemcitabine (1250mg/m(2), d1 and d8), n=32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. "Intention-to-treat" analysis included all randomized participants. RESULTS: TCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P=0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P=0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P=0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments. CONCLUSIONS: TCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression following first-line chemotherapy.

A randomized controlled pilot trial of "Feiji Recipe" on quality of life of non-small cell lung cancer patients.

In order to pilot a study observing the feasibility of applying the Core Quality of Life Questionnaire (QLQ-C30) version 2.0 to assess the quality of life (QOL) of patients with NSCLC treated with Feiji Recipe, a randomized, parallel controlled clinical trial was conducted in the university-affiliated hospital. Seventy inpatients who met the inclusion criteria were randomized into the study, and 60 cases were available as subjects for QOL data analysis. The subjects were randomly assigned to one of three groups: the Feiji Recipe group (A); the Feiji Recipe combined with chemotherapy group (B); and the chemotherapy group (C) in which the patients were treated with vinorelbine plus cisplatin (NP) or gemcitabine plus cisplatin (GP). QOL was assessed with the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Sixty cases that finished the questionnaires were analyzed, and we found that patients who received chemotherapy had low QOL, in terms of their global health, role, emotional, social, economic status and symptom burden including fatigue, nausea and vomiting, dyspnea, loss of appetite and abnormal bowel movements. Simultaneous treatment with Feiji Recipe and chemotherapy was able to prevent the worsening of function in terms of role, social, fatigue and global health. The Core Quality of Life Questionnaire (QLQ-C30) version 2.0 can be used to evaluate the QOL of patients with NSCLC treated by Chinese herbal medicine. Feiji Recipe might partially improve the QOL of NSCLC patients when administered alone or in combination with chemotherapy. No unexpected side effects were observed. However, further double-blinded placebo controlled studies are strongly recommended.

[Effect of cisplatin on expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 and their correlations in Lewis lung cancer in mice].

BACKGROUND AND OBJECTIVE: Metastasis of lung cancer is the leading cause of disease progression and treatment failure. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are related to the metastasis of lung cancer via regulating the degradation of extracellular matrix. This study was to observe the impacts of cisplatin (DDP) on the expression of MMP-9 and TIMP-1 in Lewis lung cancer, and explore their correlations and roles in metastasis. METHODS: Lewis lung cancer model was established in C57BL/6 mice. DDP group was given intraperitoneal DDP injection, and compared with normal control and tumor-bearing groups. The expression of MMP-9 and TIMP-1 were determined by ELISA in serum and detected by immunohistochemistry in tumor tissues. RESULTS: The inhibition rates of tumor growth and metastasis were 41.2% and 39.0% in DDP group, respectively. The positive rates of MMP-9 and TIMP-1 were 100% in tumor-bearing group, and their serum concentrations were significantly higher in tumor-bearing group than in normal control group (P<0.05). Serum concentrations of MMP-9 and TIMP-1, and positive rate of MMP-9 were all significantly lower in DDP group than in tumor-bearing group (P<0.05). Serum concentration of MMP-9 and positive rates of MMP-9 and TIMP-1 were positively correlated to tumor weight (r=0.665, 0.749 and 0.615, all P<0.05) and lung metastasis (r=0.668, 0.545 and 0.664, all P<0.05). MMP-9 expression was positively correlated to TIMP-1 expression both in serum and tumor (r=0.617 and 0.695, all P<0.05). The ratio of sMMP-9/TIMP-1 became a constant in normal distribution, with a mean of 1.72. CONCLUSIONS: Both MMP-9 and TIMP-1 are highly expressed in Lewis lung cancer, correlated to tumor invasion and metastasis. DDP may suppress tumor metastasis via down-regulating the expression of MMP-9 and TIMP-1 in serum and tumor.