Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties ...Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.展开更多
Lung cancer is becoming the most common cancer globally. In China, Lung cancer has become prevalent among preceding compared to present smokers. There are many treatments for lung cancer globally like Chemotherapy, Ra...Lung cancer is becoming the most common cancer globally. In China, Lung cancer has become prevalent among preceding compared to present smokers. There are many treatments for lung cancer globally like Chemotherapy, Radiotherapy, Surgery, and Targeted therapy [1] [2]. Generally, lung cancer starts in the lungs. The spongy lungs in the chest inhale oxygen and exhale carbon dioxide. Those who smoke regularly have the highest risk of lung cancer than nonsmokers. This risk increases with an increase in length, time, and the number of cigarettes smoked. Immediate treatment will help in reducing the severity of cancer. The complications of lung cancer include shortness of breath, coughing up blood, pain, and fluid in the chest. Therefore, the primary step in preventing lung cancer is quitting smoking [3].展开更多
ROS1 oncogenic fusion is reported to be 1%</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"...ROS1 oncogenic fusion is reported to be 1%</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> - </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">2% of non-small cell lung cancers (NSCLCs) of the adenocarcinoma subgroup. Meanwhile, there are no records of squamous cell cancer patients with tumors harboring ROS1 fusions. The Foundation Medicine database indicates a frequency of ROS1 rearrangements is 0.2% among squamous NSCLC. Crizotinib is known to be very effective in these patients</span><b><span style="font-family:Verdana;">.</span></b></span></span></span><span><span><b><span style="font-family:""> </span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Here we present a non-smoker patient who had pure squamous NSCLC that was treated by combinational immunotherapy under a clinical trial and progressed after 2 cycles. Surprisingly, comprehensive genomic profiling detected a rare oncogenic EZR-ROS1 fusion, and the patient was treated by crizotinib with a significant response within 6 weeks. To date, the patient has been on therapy for 42 months</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and has achieved</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a complete metabolic response.展开更多
Background: Obesity is an emerging leading cause of morbidity and mortality in the US and the relationship between obesity, tobacco, and survival in NSCLC is unclear. Methods: Data (n = 87,631) were obtained from link...Background: Obesity is an emerging leading cause of morbidity and mortality in the US and the relationship between obesity, tobacco, and survival in NSCLC is unclear. Methods: Data (n = 87,631) were obtained from linkage of the 1996-2007 Florida Cancer Data System to the Agency for Health Care Administration database providing procedure and diagnoses codes. Survival time was calculated from date of diagnosis to date of death. Smoking status was categorized as never, current, and former. Obesity (yes/no) = ICD9 code BMI > 30 kg/m2, cachexia = ICD9 code “wasting syndrome”, & non-obese = non-obese & non cachectic. Cox proportional regression models used to predict survival;demographic, clinical, treatment factors, & comorbidities were included in adjusted models with smoking status and obesity as the main factors. Results: The majority of patients (pts) were either former (49%) or current (40%) smokers, & non-obese (88%). 6.8% of pts were obese & 4.8% of pts were cachectic. There were significant differences between survival curves and median survival (months) for obese vs. non-obese vs. cachectic pts. (20 vs 10 vs. 7.9;P < 0.001). Former and current smokers had shorter median survival than never smokers (10.8 & 9.2 vs. 11.9;P < 0.001). Survival rates (%) at 1-yr (60.1 vs. 45.2 vs. 37.7;P < 0.001), 5-yr (30.3 vs. 15.4 vs. 9.5;P < 0.001), 10-yr (18.1 vs. 7.6 vs. 2.7;P < 0.001) were better for obese vs. non-obese and cachectic pts respectively. Independent predictor of worse survival in the unadjusted model was former (HR 1.08;P < 0.001) and current (HR 1.20;P < 0.001) smokers compared to never. Obese and non-obese pts had better survival vs. cachexia pts. (HR 0.52;P < 0.001 and HR 0.80, p < 0.001 respectively) and obese had better survival than Non-obese pts (HR 0.65, p < 0.001). In the adjusted model, controlling for extensive variables and comorbidities, former (HR 1.11;P < 0.001) and current (HR 1.19;P < 0.001) smokers still had significantly worse survival vs. never smokers. Obese patients still had better survival (HR 0.87;P < 0.001, and HR 0.88, p < 0.001) vs. cachexia patients and non-obese respectively, survival rate was not significantly different compare non-obese with cachexia. Conclusions: Our results show that being a former or current smoker worsens survival while obesity improved survival when compared with cachexia patients or Non-obese.展开更多
<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span...<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span "=""> </span><span>(NSCLC) have associated high dose to the heart with cardiac toxicity</span><span "=""> </span><span>and decreased overall survival</span><span "=""> </span><span>(OS). We used advanced statistical techniques</span><span "=""> </span><span>to account for correlations between dosimetric variables</span><span "=""> </span><span "=""><span>and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC.</span><b><span> Methods: </span></b><span>From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS</span></span><span "=""> </span><span>data was obtained from institutional tumor registry.</span><span "=""> </span><span>We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates.</span><span "=""> </span><span>We</span><span "=""> </span><span>subsequently used novel statistical techniques within multivariate Cox model to</span><span "=""> </span><span>systematically search the whole heart dose-volume histogram</span><span "=""> </span><span>(DVH) for dose parameters</span><span "=""> </span><span "=""><span>associated with OS.</span><b><span> Results: </span></b><span>Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH</span></span><span>,</span><span> the dose of</span><span "=""> </span><span>51</span><span "=""> </span><span>Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified</span><span "=""> </span><span>V55Gy (percentage of the whole heart volume receiving at least</span><span "=""> </span><span>55</span><span "=""> </span><span>Gy) as the best single DVH index which can be used to set treatment optimization constraints</span><span "=""> </span><span>(Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55</span><span "=""> </span><span>Gy, P</span><span "=""> </span><span>=</span><span "=""> </span><span>0.03). Additional characteristics correlated with OS on multivariate analysis were</span><span "=""> </span><span "=""><span>age, stage (IIIA/IIIB), and administration of chemotherapy. </span><b><span>Conclusion:</span></b><span> Doses above 51</span></span><span "=""> </span><span>Gy, applied to</span><span "=""> </span><span>small volumes of the heart,</span><span "=""> </span><span>are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS</span><span>.</span>展开更多
<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiati...<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.</span></span></span>展开更多
Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people's quality of life. Feiji Reci...Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people's quality of life. Feiji Recipe is an empirical formula and has been used as a treatment for non-small cell lung cancer(NSCLC) for many years. This thesis collects data of the etiology and pathogenesis of Feiji Recipe, clinical research and animal experiments,and provide suggestive evidence of Feiji Recipe for treating NSCLC. During the treatment, the characteristic of holism and personalized treatment of traditional Chinese medicine(TCM)is proved, which also demonstrated that it can relieve patient's clinical syndrome, improve their quality of life and enhance the body immunity. It plays an irreplaceable role in lung cancer treatment.展开更多
Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer(NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and t...Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer(NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins(HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmen-tal or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1's role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.展开更多
Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status...Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status,the mechanisms involved are largely unknown.In this study,we showed that mi R-124,a tumor suppressor,was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines.In addition,the mi R-124 depletion induced gefitinib resistance,and mi R-124 overexpression sensitized gefitinib-resistant cells to gefitinib.Mechanistic analysis revealed that mi R-124 decreased SNAI2 and STAT3 expression by directly targeting their 3'UTRs and that knocking down SNAI2 or STAT3 partly reversed the gefitinib resistance induced by mi R-124 depletion.Our data demonstrate that the mi R-124 plays a new critical role in acquired resistance to gefitinib and that the manipulation of mi R-124 might provide a therapeutic strategy for reversing acquired gefitinib resistance.展开更多
With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cance...With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cancer(NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations(co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate(DCR) was 93.7% with two patients(0.2%) achieving complete response(CR), the median progression free survival(PFS) was 13.0 months(95% confidence interval [CI], 11.6–14.4 months), and the median overall survival(OS) was 55.0 months(95% CI, 26.3–83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation(P<0.001). Patients with classic mutations(del-19 and/or L858 R mutations) demonstrated longer PFS(P<0.001) and OS(P=0.017) than those with uncommon mutations(single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS(hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P<0.001) and OS(HR=0.221, 95% CI, 0.101–0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations(especially for the patients with single rare mutations) are needed to determine a better precision treatment.展开更多
Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had ...Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.展开更多
In recent years, the incidence of lung adenocarcinoma has been increasing, </span><span style="font-family:Verdana;">and now it has become the largest type of non-small cell lung cancer (NSCLC)&l...In recent years, the incidence of lung adenocarcinoma has been increasing, </span><span style="font-family:Verdana;">and now it has become the largest type of non-small cell lung cancer (NSCLC)</span><span style="font-family:Verdana;">. Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new mo</span><span style="font-family:Verdana;">lecular subtypes, the search for tumor driver gene mutations, the developmen</span><span style="font-family:Verdana;">t </span><span style="font-family:Verdana;">of targeted molecular targeted drugs, or targeted therapy to suppress tumor angioge</span><span style="font-family:Verdana;">nesis and regulate tumor immune response have been the main directio</span><span style="font-family:Verdana;">ns of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clini</span><span style="font-family:Verdana;">cally. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.展开更多
OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferatio...OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis,respectively.Immunofluorescence staining and cathepsin activity assay were used to detect autophagy.Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels.Xenograft experiments were applied for in vivo evaluation.RESULTS Cepharanthine,a natural compound,increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells.Numerous yellow puncta were observed in cepharanthine-treated cells with m RFP-EGFP-LC3 transfection.Co-staining of GFP-LC3 with LysoT racker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes-lysosomes fusion.Moreover,cepharanthine attenuated the lysosomal cathepsins maturation.We also confirmed that dacomitinib induced cytoprotective autophagy.Combined treatment with cepharanthine increased the anti-cancer effects of dacomitinib in vitro and in vivo.Besides,cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells.CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor,and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.展开更多
Objective: Adjuvant chemotherapy(AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer(NSCLC); however, few studies have reported the correlation between the time to...Objective: Adjuvant chemotherapy(AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer(NSCLC); however, few studies have reported the correlation between the time to initiation of AC(TTAC) and survival in NSCLC patients.Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed.TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival(DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching(PSM) was performed for survival analysis using the match data.Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A(≤35 d) and group B(>35 d). There was no significant difference in the DFS between the two groups(P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs(P=0.283).Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.展开更多
Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associat...Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.Methods:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)database.We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes.By overlapping analysis,epigenetically modulated metastasis-associated genes were obtained.Kaplan-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung cancer.Immunohistochemistry(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical indicators.Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis.The regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays.Results:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation.The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer.IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage.Loss-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells.Furthermore,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples.The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.Conclusions:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.展开更多
Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms o...Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms of its anatomical,biological and patient characteristics.Prognostic factors based on patient characteristics were not well determined yet in this subgroup,and there is currently no standard treatment recommendation for these heterogeneous pN2 subjects.Apparent disagreements and inconsistency exist in study reports concerning the prognostic significance of certain factors in pN2 NSCLC,especially regarding to the issue about whether skip N2 metastasis benefit from surgery.Methods We therefore performed this comprehensive summary of the published literatures to draw a more precise and less uncertain conclusion.After a comprehensive literature search,a total of 73 studies involving 23,773 subjects were included according to eligibility criteria.Results As expected,most of the investigated factors,such as old age,male,advanced pathological T stage,advanced clinical N stage,multiple N2 stations,extended surgical resection(pneumonectomy),and incomplete resection,but not post-operation treatment(eg.chemotherapy and radiotherapy)were significantly associated with poor survival.However,skip N2 metastasis was favourable prognostic factors in operable pN2 NSCLC subjects.Other factors(histological type and primary tumour side)were neutral in terms of association with overall survival.We highlighted a number of important prognostic factors for pN2 NSCLC patients.Particularly,patients with skip N2 disease benefit from surgery.Conclusion Our findings could be used as reference information for decision-making in clinical practice and future study design.展开更多
Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plu...Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m<sup>2</sup>) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m<sup>2</sup>) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.展开更多
<strong>Objective:</strong> To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different ti...<strong>Objective:</strong> To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. <strong>Methods:</strong> A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. <strong>Results:</strong> NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. <strong>Conclusion:</strong> In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.展开更多
Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-I...Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-IFJ group were irradiated to large-field target volume by a daily fraction of 2Gy, and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of large-field target volume was SOGy/25Fx/SW and of small-field target volume was 7SGy/SOFx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy/33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery (CR), partial recovery (PR), and no change (NC) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR,PR,NC in AHFI group and CFI group were 22.9%(8/35), 60.0%(21/35), 17.1%(6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0. 05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35), 31 .4% (11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P< 0.05). The incidences of esophagitis and pneumonitis in AHFI group and CFI group were 34.3% (12/35), 22. 9% (8/35) and 40.0% (14/35), 17.1% (6/35)(P>0. 05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year sur-vival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.展开更多
Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Thr...Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/mL, AUC (12 127.39±636.16)ng·h/mL and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.展开更多
文摘Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.
文摘Lung cancer is becoming the most common cancer globally. In China, Lung cancer has become prevalent among preceding compared to present smokers. There are many treatments for lung cancer globally like Chemotherapy, Radiotherapy, Surgery, and Targeted therapy [1] [2]. Generally, lung cancer starts in the lungs. The spongy lungs in the chest inhale oxygen and exhale carbon dioxide. Those who smoke regularly have the highest risk of lung cancer than nonsmokers. This risk increases with an increase in length, time, and the number of cigarettes smoked. Immediate treatment will help in reducing the severity of cancer. The complications of lung cancer include shortness of breath, coughing up blood, pain, and fluid in the chest. Therefore, the primary step in preventing lung cancer is quitting smoking [3].
文摘ROS1 oncogenic fusion is reported to be 1%</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> - </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">2% of non-small cell lung cancers (NSCLCs) of the adenocarcinoma subgroup. Meanwhile, there are no records of squamous cell cancer patients with tumors harboring ROS1 fusions. The Foundation Medicine database indicates a frequency of ROS1 rearrangements is 0.2% among squamous NSCLC. Crizotinib is known to be very effective in these patients</span><b><span style="font-family:Verdana;">.</span></b></span></span></span><span><span><b><span style="font-family:""> </span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Here we present a non-smoker patient who had pure squamous NSCLC that was treated by combinational immunotherapy under a clinical trial and progressed after 2 cycles. Surprisingly, comprehensive genomic profiling detected a rare oncogenic EZR-ROS1 fusion, and the patient was treated by crizotinib with a significant response within 6 weeks. To date, the patient has been on therapy for 42 months</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and has achieved</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">a complete metabolic response.
文摘Background: Obesity is an emerging leading cause of morbidity and mortality in the US and the relationship between obesity, tobacco, and survival in NSCLC is unclear. Methods: Data (n = 87,631) were obtained from linkage of the 1996-2007 Florida Cancer Data System to the Agency for Health Care Administration database providing procedure and diagnoses codes. Survival time was calculated from date of diagnosis to date of death. Smoking status was categorized as never, current, and former. Obesity (yes/no) = ICD9 code BMI > 30 kg/m2, cachexia = ICD9 code “wasting syndrome”, & non-obese = non-obese & non cachectic. Cox proportional regression models used to predict survival;demographic, clinical, treatment factors, & comorbidities were included in adjusted models with smoking status and obesity as the main factors. Results: The majority of patients (pts) were either former (49%) or current (40%) smokers, & non-obese (88%). 6.8% of pts were obese & 4.8% of pts were cachectic. There were significant differences between survival curves and median survival (months) for obese vs. non-obese vs. cachectic pts. (20 vs 10 vs. 7.9;P < 0.001). Former and current smokers had shorter median survival than never smokers (10.8 & 9.2 vs. 11.9;P < 0.001). Survival rates (%) at 1-yr (60.1 vs. 45.2 vs. 37.7;P < 0.001), 5-yr (30.3 vs. 15.4 vs. 9.5;P < 0.001), 10-yr (18.1 vs. 7.6 vs. 2.7;P < 0.001) were better for obese vs. non-obese and cachectic pts respectively. Independent predictor of worse survival in the unadjusted model was former (HR 1.08;P < 0.001) and current (HR 1.20;P < 0.001) smokers compared to never. Obese and non-obese pts had better survival vs. cachexia pts. (HR 0.52;P < 0.001 and HR 0.80, p < 0.001 respectively) and obese had better survival than Non-obese pts (HR 0.65, p < 0.001). In the adjusted model, controlling for extensive variables and comorbidities, former (HR 1.11;P < 0.001) and current (HR 1.19;P < 0.001) smokers still had significantly worse survival vs. never smokers. Obese patients still had better survival (HR 0.87;P < 0.001, and HR 0.88, p < 0.001) vs. cachexia patients and non-obese respectively, survival rate was not significantly different compare non-obese with cachexia. Conclusions: Our results show that being a former or current smoker worsens survival while obesity improved survival when compared with cachexia patients or Non-obese.
文摘<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span "=""> </span><span>(NSCLC) have associated high dose to the heart with cardiac toxicity</span><span "=""> </span><span>and decreased overall survival</span><span "=""> </span><span>(OS). We used advanced statistical techniques</span><span "=""> </span><span>to account for correlations between dosimetric variables</span><span "=""> </span><span "=""><span>and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC.</span><b><span> Methods: </span></b><span>From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS</span></span><span "=""> </span><span>data was obtained from institutional tumor registry.</span><span "=""> </span><span>We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates.</span><span "=""> </span><span>We</span><span "=""> </span><span>subsequently used novel statistical techniques within multivariate Cox model to</span><span "=""> </span><span>systematically search the whole heart dose-volume histogram</span><span "=""> </span><span>(DVH) for dose parameters</span><span "=""> </span><span "=""><span>associated with OS.</span><b><span> Results: </span></b><span>Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH</span></span><span>,</span><span> the dose of</span><span "=""> </span><span>51</span><span "=""> </span><span>Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified</span><span "=""> </span><span>V55Gy (percentage of the whole heart volume receiving at least</span><span "=""> </span><span>55</span><span "=""> </span><span>Gy) as the best single DVH index which can be used to set treatment optimization constraints</span><span "=""> </span><span>(Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55</span><span "=""> </span><span>Gy, P</span><span "=""> </span><span>=</span><span "=""> </span><span>0.03). Additional characteristics correlated with OS on multivariate analysis were</span><span "=""> </span><span "=""><span>age, stage (IIIA/IIIB), and administration of chemotherapy. </span><b><span>Conclusion:</span></b><span> Doses above 51</span></span><span "=""> </span><span>Gy, applied to</span><span "=""> </span><span>small volumes of the heart,</span><span "=""> </span><span>are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS</span><span>.</span>
文摘<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.</span></span></span>
文摘Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people's quality of life. Feiji Recipe is an empirical formula and has been used as a treatment for non-small cell lung cancer(NSCLC) for many years. This thesis collects data of the etiology and pathogenesis of Feiji Recipe, clinical research and animal experiments,and provide suggestive evidence of Feiji Recipe for treating NSCLC. During the treatment, the characteristic of holism and personalized treatment of traditional Chinese medicine(TCM)is proved, which also demonstrated that it can relieve patient's clinical syndrome, improve their quality of life and enhance the body immunity. It plays an irreplaceable role in lung cancer treatment.
基金Supported by Grants from the National Science Council,Taiwan,ROCin part by the Ministry of Education,Taiwan,ROC under the ATU plan
文摘Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer(NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins(HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmen-tal or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1's role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.
基金supported by the grants from National Natural Science Foundation of China(No.81301899 and 81372662)Wu Jie Ping Medical Foundation(No.320.6750.1239)the Special Funds for Major State Basic Research Program of China(973 Program)(No.2009CB521802)
文摘Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status,the mechanisms involved are largely unknown.In this study,we showed that mi R-124,a tumor suppressor,was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines.In addition,the mi R-124 depletion induced gefitinib resistance,and mi R-124 overexpression sensitized gefitinib-resistant cells to gefitinib.Mechanistic analysis revealed that mi R-124 decreased SNAI2 and STAT3 expression by directly targeting their 3'UTRs and that knocking down SNAI2 or STAT3 partly reversed the gefitinib resistance induced by mi R-124 depletion.Our data demonstrate that the mi R-124 plays a new critical role in acquired resistance to gefitinib and that the manipulation of mi R-124 might provide a therapeutic strategy for reversing acquired gefitinib resistance.
基金supported by grants from the National Natural Science Foundation of China(No.81372407)Health and Family Planning Scientific Research Project of Hubei Province(No.WJ2017Q007)
文摘With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cancer(NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations(co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate(DCR) was 93.7% with two patients(0.2%) achieving complete response(CR), the median progression free survival(PFS) was 13.0 months(95% confidence interval [CI], 11.6–14.4 months), and the median overall survival(OS) was 55.0 months(95% CI, 26.3–83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation(P<0.001). Patients with classic mutations(del-19 and/or L858 R mutations) demonstrated longer PFS(P<0.001) and OS(P=0.017) than those with uncommon mutations(single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS(hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P<0.001) and OS(HR=0.221, 95% CI, 0.101–0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations(especially for the patients with single rare mutations) are needed to determine a better precision treatment.
文摘Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.
文摘In recent years, the incidence of lung adenocarcinoma has been increasing, </span><span style="font-family:Verdana;">and now it has become the largest type of non-small cell lung cancer (NSCLC)</span><span style="font-family:Verdana;">. Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new mo</span><span style="font-family:Verdana;">lecular subtypes, the search for tumor driver gene mutations, the developmen</span><span style="font-family:Verdana;">t </span><span style="font-family:Verdana;">of targeted molecular targeted drugs, or targeted therapy to suppress tumor angioge</span><span style="font-family:Verdana;">nesis and regulate tumor immune response have been the main directio</span><span style="font-family:Verdana;">ns of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clini</span><span style="font-family:Verdana;">cally. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.
基金supported by Science and Technology Development Fund,Macao S.A.R(FDCT)(024/2016/A1)Research Fund of University of Macao(MYRG2015-00091-ICMS-QRCM and MYRG2015-00101-ICMS-QRCM)
文摘OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis,respectively.Immunofluorescence staining and cathepsin activity assay were used to detect autophagy.Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels.Xenograft experiments were applied for in vivo evaluation.RESULTS Cepharanthine,a natural compound,increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells.Numerous yellow puncta were observed in cepharanthine-treated cells with m RFP-EGFP-LC3 transfection.Co-staining of GFP-LC3 with LysoT racker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes-lysosomes fusion.Moreover,cepharanthine attenuated the lysosomal cathepsins maturation.We also confirmed that dacomitinib induced cytoprotective autophagy.Combined treatment with cepharanthine increased the anti-cancer effects of dacomitinib in vitro and in vivo.Besides,cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells.CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor,and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.
文摘Objective: Adjuvant chemotherapy(AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer(NSCLC); however, few studies have reported the correlation between the time to initiation of AC(TTAC) and survival in NSCLC patients.Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed.TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival(DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching(PSM) was performed for survival analysis using the match data.Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A(≤35 d) and group B(>35 d). There was no significant difference in the DFS between the two groups(P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs(P=0.283).Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.
基金supported by the National Natural Science Foundation of China (No. 81602576, 81802872)National Key Research and Development Program of China (No. 2016YFA0201503)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (No. 2016I2M-1-007, 2018-I2M-1-002)
文摘Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.Methods:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)database.We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes.By overlapping analysis,epigenetically modulated metastasis-associated genes were obtained.Kaplan-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung cancer.Immunohistochemistry(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical indicators.Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis.The regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays.Results:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation.The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer.IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage.Loss-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells.Furthermore,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples.The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.Conclusions:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.
基金grants from the National Basic Research Program of China(973 ProgramNo.2012CB720605)the Zhongnan Hospital of Wuhan University Science,Technology and Innovation Seed Fund(No.znpy2016046).
文摘Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms of its anatomical,biological and patient characteristics.Prognostic factors based on patient characteristics were not well determined yet in this subgroup,and there is currently no standard treatment recommendation for these heterogeneous pN2 subjects.Apparent disagreements and inconsistency exist in study reports concerning the prognostic significance of certain factors in pN2 NSCLC,especially regarding to the issue about whether skip N2 metastasis benefit from surgery.Methods We therefore performed this comprehensive summary of the published literatures to draw a more precise and less uncertain conclusion.After a comprehensive literature search,a total of 73 studies involving 23,773 subjects were included according to eligibility criteria.Results As expected,most of the investigated factors,such as old age,male,advanced pathological T stage,advanced clinical N stage,multiple N2 stations,extended surgical resection(pneumonectomy),and incomplete resection,but not post-operation treatment(eg.chemotherapy and radiotherapy)were significantly associated with poor survival.However,skip N2 metastasis was favourable prognostic factors in operable pN2 NSCLC subjects.Other factors(histological type and primary tumour side)were neutral in terms of association with overall survival.We highlighted a number of important prognostic factors for pN2 NSCLC patients.Particularly,patients with skip N2 disease benefit from surgery.Conclusion Our findings could be used as reference information for decision-making in clinical practice and future study design.
文摘Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m<sup>2</sup>) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m<sup>2</sup>) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.
文摘<strong>Objective:</strong> To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. <strong>Methods:</strong> A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. <strong>Results:</strong> NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. <strong>Conclusion:</strong> In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.
文摘Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-IFJ group were irradiated to large-field target volume by a daily fraction of 2Gy, and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of large-field target volume was SOGy/25Fx/SW and of small-field target volume was 7SGy/SOFx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy/33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery (CR), partial recovery (PR), and no change (NC) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR,PR,NC in AHFI group and CFI group were 22.9%(8/35), 60.0%(21/35), 17.1%(6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0. 05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35), 31 .4% (11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P< 0.05). The incidences of esophagitis and pneumonitis in AHFI group and CFI group were 34.3% (12/35), 22. 9% (8/35) and 40.0% (14/35), 17.1% (6/35)(P>0. 05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year sur-vival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.
基金This work was supported by grant from Science Investigation Fund of Ministry of Health of China(No96-1-250)
文摘Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/mL, AUC (12 127.39±636.16)ng·h/mL and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.
