BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate ...BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.展开更多
BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated ann...Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.展开更多
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
BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limit...BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.展开更多
Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung...Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.展开更多
Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effec...Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.展开更多
BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We ...BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.展开更多
Background: Video-assisted thoracic surgery (VATS) has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer (NSCLC). However, popularization of this relativ...Background: Video-assisted thoracic surgery (VATS) has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer (NSCLC). However, popularization of this relatively novel technique has been slow, partly due to concerns about its long-term outcomes. The present study aimed to evaluate the long-term survival outcomes of patients with NSCLC after VATS, and to determine the significant prognostic factors on overall survival. Methods: Consecutive patients diagnosed with NSCLC referred to one institution for VATS were identified from a central database. Patients were treated by either complete-VATS or assisted-VATS, as described in previous studies. A number of baseline patient characteristics, clinicopathologic data and treatment-related factors were analyzed as potential prognostic factors on overall survival. Results: Between January 2000 and December 2007, 1,139 patients with NSCLC who underwent VATS and fulfilled a set of predetermined inclusion criteria were included for analysis. The median age of the entire group was 60 years, with 791 male patients (69%). The median 5-year overall survival for Stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease according to the recently updated TNM classification system were 72.2%, 47.5%, 29.8% and 28.6%, respectively. Female gender, TNM stage, pT status, and type of resection were found to be significant prognostic factors on multivariate analysis. Conclusions: VATS offers a viable alternative to conventional open thoracotomy for selected patients with clinically resectableNSCLC展开更多
Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung...Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32-85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (No), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P〉0.05). In lymph node negative patients (No), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1-2). The difference was significant (P〈0,01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P〉0.05). Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.展开更多
Background: Patient-reported outcomes of the quality of life (QOL) after an open thoracotomy have not been studied. To determine the physical and mental changes in surgical patients is very important for medical staff...Background: Patient-reported outcomes of the quality of life (QOL) after an open thoracotomy have not been studied. To determine the physical and mental changes in surgical patients is very important for medical staffs. The surgical patient’s satisfaction and overall healthy changes were evaluated by the patient-self assessment questionnaires. Materials and Methods: From July 2007 to April 2008, 26 patients with non-small cell lung cancer (NSCLC) underwent surgical resection. The outcome of the QOL was evaluated by using two kinds of questionnaire surveys from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the anti-aging QOL assessment (AA-QOL). The EORTC QLQ-C30 consisted of five domains (physical, role, cognitive, emotional, and social functionings) and global QOL. The AA-QOL contained 51 items;30 physical and 21 mental symptoms regarding the elderly and the aging population. The patients replied to the two questionnaires at two different times, i.e., at pre-surgery (baseline) and at post-surgery (2 weeks after the operation). The obtained data of these scores were averaged and compared between the two points of the pre-surgery and post-surgery. Results: Regarding the outcomes of the EORTC QLQ-C30, the physical and social functioning became significantly worse after the surgery. In contrast, the global QOL significantly became better after the surgery. For the symptom at post-surgery, three of which were “nausea and vomiting”, “pain”, and “appetite loss”, became significantly worse compared to those at pre-surgery. Regarding the outcomes of the AA-QOL, the physical symptoms (muscular pain/stiffness, palpitations, dyspnea, no feeling of good health, anorexia, and coughing and sputum) became significantly worse after the surgery. Regarding the mental symptoms, there were no significant differences. Conclusions: Regarding the outcomes based on the changes in the QOL after surgery, the physical symptoms became worse compared to the mental symptoms. To clarify the perioperative healthy changes of the QOL reported by patients with lung cancers is very important for multidisciplinary teamwork, which should play a role in providing the appropriate care and treatment and useful information for a preoperative patient’s decision making of receiving surgical treatment.展开更多
Lobectomy with partial removal of the pulmonary artery in video-assisted thoracic surgery (VATS) currently remains a challenge for thoracic surgeons. We were interested in introducing pulmonary vessel blocking techn...Lobectomy with partial removal of the pulmonary artery in video-assisted thoracic surgery (VATS) currently remains a challenge for thoracic surgeons. We were interested in introducing pulmonary vessel blocking techniques in open thoracic surgery into video-assisted thoracic surgery (VATS) procedures. In this study, we reported a surgical technique simultaneously blocking the pulmonary artery and the pulmonary vein for partial removal of the pulmonary artery under VATS. Seven patients with non-small-cell lung cancer (NSCLC) received lobectomy with partial removal of the pulmonary artery using the technique between December 2007 and March 2012. Briefly, rather than using a small clamp on the distal pulmonary artery to the area of invading cancer, we replaced a vascular clamp with a ribbon and Hem-o-lock clip to block the preserved pulmonary veins so as to prevent back bleeding and yield a better view for surgeons. The mean occlusion time of the pulmonary artery and pulmonary veins were 44.0±10.0 and 41.3±9.7 minutes, respectively. The mean repair time of the pulmonary artery was 25.3±13.7 minutes. No complications occurred. No patients showed abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. In conclusion, the technique for blocking the pulmonary artery and veins is feasible and safe in VATS and reduces the risk of abrupt intraoperative bleeding and the chance of converting to open thoracotomy, and extends the indications of VATS lobectomy.展开更多
In order to explore the possibility to predict the risk factors for postoperative complications and survival time, the clinical data of 152 patients (including 116 males and 36 females) who had undergone neo-adjuvan...In order to explore the possibility to predict the risk factors for postoperative complications and survival time, the clinical data of 152 patients (including 116 males and 36 females) who had undergone neo-adjuvant therapy and surgery for stage IIIA and B non-small cell lung cancer (NSCLC) were retrospectively analyzed. Demographic data, preoperative functional parameters, staging, induction regimen (chemotherapy alone or associated with radiotherapy), associated disorders, and data about operation were collected. Chi-square test and multivariate analysis fitting the unconditional logistic regression model were performed to identify predictors of postoperative complications, while Kaplan-Meier and multivariate Cox proportional hazard model were employed to identify predictors of survival time, respectively. The univariate analysis demonstrated that forced expiratory volume in 1 second predicted percent (FEV1%, P=0.040) and associated disorders (P=0.020) were the predictive factors of complications, but multivariate analysis found no independence factors (P〉0.05) of it. Univariate Kaplan-Meier analysis showed that stage (P=0.050) and pneumonectomy (P=0.018) affected the survival time. However, multivariate Cox proportional hazard model analysis demonstrated that only pneumonectomy (P=0.026) was associated with a decreased survival time, but no differences between right and left pneumonectomy were found. The results suggest that the risk factor for postoperative complications is acceptable, and pneumonectomy is associated with increased mortality, which should be performed only in stage Ⅲ NSCLC patients.展开更多
As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer of...As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.展开更多
Objective The aim of this study was to study the quantitative expression of circulating tumour DNA(ctDNA) in patients with non-small cell lung cancer(NSCLC) before and after radical operation and to explore the correl...Objective The aim of this study was to study the quantitative expression of circulating tumour DNA(ctDNA) in patients with non-small cell lung cancer(NSCLC) before and after radical operation and to explore the correlation between gene mutations in non-small cell lung cancer tissues and those in ctDNA.Methods We randomly assigned 5 NSCLC patients from the Department of Thoracic Surgery of Fujian Medical University Union Hospital. All the patients had undergone radical surgery. Venous blood samples were collected from the 5 NSCLC patients at two time points(before the operation and 21–37 days after the operation) for monitoring ctDNA levels. This was done by isolating plasma from venous blood using high velocity centrifugation, extracting DNA from the plasma using the QIAamp Circulating Nucleic Acid kit, and then quantifying the ctDNA levels. The results were analyzed using the Wilcoxon Rank Sum Test. Moreover, the ctDNA levels were compared with those of carcinoembryonic antigen(CEA), which was detected simultaneously with the ctDNA. Then, DNA samples from the tumor tissues and peripheral blood cells and ctDNA were sequenced using the Hiseq2000 sequencing platform(Illumina) and the mutant genes were screened out. Mutations that occurred within the tumor tissues were used as positive control, whereas those found in the pre-operative blood cells were used as a negative control. Based on the mutational analysis of ctDNA genes, a total of 508 cancer-related genes were screened. Results The median values of the pre-and post-operative ctDNA levels in the 5 patients with NSCLC were 0.612(0.518–0.876) and 0.430(0.372–0.612) ng/μL, respectively. There was a significant difference between the two groups(P < 0.05). The pre-operative CEA level was slightly higher than the post-operative level(P > 0.05). In one of the cases, LC tissues showed multiple mutations, consistent with pre-operative ctDNA. Moreover, isogenic mutations of the same type were not detected in post-operative ctDNA or peripheral blood cells. Conclusion Mutations found in the lung cancer(LC) ctDNA gene were consistent with the mutation type of LC tissue. Hence, the quantitative and qualitative analysis of ctDNA is a promising novel molecular biomarker for the evaluation of tumor burden changes in NSCLC.展开更多
Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues pu...Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.展开更多
Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtaine...Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtained from a single patient at different time points during treatment allows for the investigation of the changes in gene expression prior to (GLC14) and following cycles of chemotherapy and irradiation (GLC19). GLC19 cells were reported to reveal an increased doubling time and exhibit increased chemoresistance to doxorubicin, etoposide, melphalan and vinblastine. Upregulated transcripts in GLC19, as assessed by microarray analysis, comprised proteins involved in regulation of cellular growth (NGFRAP1/BEX3), adhesion, glutathione metabolism and, in particular, WNT/Notch pathways and the putative cancer stem cell phenotype (CD44, ALDH1A1, and AKR1C1/13). Metallothioneins, tubulins TUBA3/4 and tumor protein p53 inducible protein 11 (TP53IP11) were downregulated in this cell line compared to GLC14. Except increased expression of glutathione transferases no classical markers of chemoresistance were found, pointing to a role of altered growth control/differentiation and reduced accessibility of this SCLC tumor cells growing as multicellular spheroids. In conclusion, treatment of this single SCLC with cyclophosphamide, doxorubicin and etoposide (CDE) followed by radiotherapy ultimately resulted in an enrichment of tumor cells displaying the typical signature of tumor-initiating or cancer stem cells (CIC/CSC).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
To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who...To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage III-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB (25 mg/m^2, D1, D5)/paclitaxel (175 mg/m^2, D1) and Carboplatin (AUC=5, D1). Results: In chemotherapy group, 75.8% (68/79) of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy. Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group (897 d vs 821 d, P=0.0527), but there was significant difference in the 1-year and 2-year overall survival (94.71%, 76.28% vs 512 d, P=0.122), but there was significant difference in the 2-year survival rate between two groups with brain metastases (66.7% vs 37.6% P〈0.05). The median survival after brain metastasis appeared was 190 days. Conclusion: Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage II-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.展开更多
Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized ...Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 dl, cisplatin (DDP) 20 mg/m2, d1–5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600–900 mg/d for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage III was 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage I–II in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage III, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.展开更多
基金Supported by the Scientific Research Foundation of Peking University Shenzhen Hospital,No.KYQD2021096the National Natural Science Foundation of China,No.81972829Precision Medicine Research Program of Tsinghua University,No.2022ZLA006.
文摘BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
文摘Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. Mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of Mohs procedure for being the acclaimed gold standard.
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.
基金Supported by the Foundation of Science and Technology Bureau of Dalian,No. 2021JJ13SN70。
文摘BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.
文摘Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.
文摘Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.
文摘BACKGROUND Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors,which present significant challenges in terms of diagnosis and treatment.CASE SUMMARY We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man.Transbronchial lung biopsy revealed squamous cell carcinoma.Although enlargement of lymph node 12u was detected,no distant metastases were observed.The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection(ND2a).Based on histopathological findings,the primary lesion was squamous cell carcinoma.A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion.Tumors were detected in two resected lymph nodes(#12u and#11s).Both tumors were pathologically diagnosed as small cell carcinomas.The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging;however,chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.CONCLUSION Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.
文摘Background: Video-assisted thoracic surgery (VATS) has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer (NSCLC). However, popularization of this relatively novel technique has been slow, partly due to concerns about its long-term outcomes. The present study aimed to evaluate the long-term survival outcomes of patients with NSCLC after VATS, and to determine the significant prognostic factors on overall survival. Methods: Consecutive patients diagnosed with NSCLC referred to one institution for VATS were identified from a central database. Patients were treated by either complete-VATS or assisted-VATS, as described in previous studies. A number of baseline patient characteristics, clinicopathologic data and treatment-related factors were analyzed as potential prognostic factors on overall survival. Results: Between January 2000 and December 2007, 1,139 patients with NSCLC who underwent VATS and fulfilled a set of predetermined inclusion criteria were included for analysis. The median age of the entire group was 60 years, with 791 male patients (69%). The median 5-year overall survival for Stage Ⅰ, Ⅱ, Ⅲ and Ⅳ disease according to the recently updated TNM classification system were 72.2%, 47.5%, 29.8% and 28.6%, respectively. Female gender, TNM stage, pT status, and type of resection were found to be significant prognostic factors on multivariate analysis. Conclusions: VATS offers a viable alternative to conventional open thoracotomy for selected patients with clinically resectableNSCLC
文摘Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32-85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (No), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P〉0.05). In lymph node negative patients (No), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1-2). The difference was significant (P〈0,01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P〉0.05). Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.
文摘Background: Patient-reported outcomes of the quality of life (QOL) after an open thoracotomy have not been studied. To determine the physical and mental changes in surgical patients is very important for medical staffs. The surgical patient’s satisfaction and overall healthy changes were evaluated by the patient-self assessment questionnaires. Materials and Methods: From July 2007 to April 2008, 26 patients with non-small cell lung cancer (NSCLC) underwent surgical resection. The outcome of the QOL was evaluated by using two kinds of questionnaire surveys from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the anti-aging QOL assessment (AA-QOL). The EORTC QLQ-C30 consisted of five domains (physical, role, cognitive, emotional, and social functionings) and global QOL. The AA-QOL contained 51 items;30 physical and 21 mental symptoms regarding the elderly and the aging population. The patients replied to the two questionnaires at two different times, i.e., at pre-surgery (baseline) and at post-surgery (2 weeks after the operation). The obtained data of these scores were averaged and compared between the two points of the pre-surgery and post-surgery. Results: Regarding the outcomes of the EORTC QLQ-C30, the physical and social functioning became significantly worse after the surgery. In contrast, the global QOL significantly became better after the surgery. For the symptom at post-surgery, three of which were “nausea and vomiting”, “pain”, and “appetite loss”, became significantly worse compared to those at pre-surgery. Regarding the outcomes of the AA-QOL, the physical symptoms (muscular pain/stiffness, palpitations, dyspnea, no feeling of good health, anorexia, and coughing and sputum) became significantly worse after the surgery. Regarding the mental symptoms, there were no significant differences. Conclusions: Regarding the outcomes based on the changes in the QOL after surgery, the physical symptoms became worse compared to the mental symptoms. To clarify the perioperative healthy changes of the QOL reported by patients with lung cancers is very important for multidisciplinary teamwork, which should play a role in providing the appropriate care and treatment and useful information for a preoperative patient’s decision making of receiving surgical treatment.
文摘Lobectomy with partial removal of the pulmonary artery in video-assisted thoracic surgery (VATS) currently remains a challenge for thoracic surgeons. We were interested in introducing pulmonary vessel blocking techniques in open thoracic surgery into video-assisted thoracic surgery (VATS) procedures. In this study, we reported a surgical technique simultaneously blocking the pulmonary artery and the pulmonary vein for partial removal of the pulmonary artery under VATS. Seven patients with non-small-cell lung cancer (NSCLC) received lobectomy with partial removal of the pulmonary artery using the technique between December 2007 and March 2012. Briefly, rather than using a small clamp on the distal pulmonary artery to the area of invading cancer, we replaced a vascular clamp with a ribbon and Hem-o-lock clip to block the preserved pulmonary veins so as to prevent back bleeding and yield a better view for surgeons. The mean occlusion time of the pulmonary artery and pulmonary veins were 44.0±10.0 and 41.3±9.7 minutes, respectively. The mean repair time of the pulmonary artery was 25.3±13.7 minutes. No complications occurred. No patients showed abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. In conclusion, the technique for blocking the pulmonary artery and veins is feasible and safe in VATS and reduces the risk of abrupt intraoperative bleeding and the chance of converting to open thoracotomy, and extends the indications of VATS lobectomy.
基金supported by a grant for Doctoral Program of Education Ministry (No. 20060487046).
文摘In order to explore the possibility to predict the risk factors for postoperative complications and survival time, the clinical data of 152 patients (including 116 males and 36 females) who had undergone neo-adjuvant therapy and surgery for stage IIIA and B non-small cell lung cancer (NSCLC) were retrospectively analyzed. Demographic data, preoperative functional parameters, staging, induction regimen (chemotherapy alone or associated with radiotherapy), associated disorders, and data about operation were collected. Chi-square test and multivariate analysis fitting the unconditional logistic regression model were performed to identify predictors of postoperative complications, while Kaplan-Meier and multivariate Cox proportional hazard model were employed to identify predictors of survival time, respectively. The univariate analysis demonstrated that forced expiratory volume in 1 second predicted percent (FEV1%, P=0.040) and associated disorders (P=0.020) were the predictive factors of complications, but multivariate analysis found no independence factors (P〉0.05) of it. Univariate Kaplan-Meier analysis showed that stage (P=0.050) and pneumonectomy (P=0.018) affected the survival time. However, multivariate Cox proportional hazard model analysis demonstrated that only pneumonectomy (P=0.026) was associated with a decreased survival time, but no differences between right and left pneumonectomy were found. The results suggest that the risk factor for postoperative complications is acceptable, and pneumonectomy is associated with increased mortality, which should be performed only in stage Ⅲ NSCLC patients.
基金supported by the National Natural Science Foun-dation of China(grant numbers 81974483 and 82072589)the ChineseSocietyofClinicalOncology-HengruiCancerResearch Fund(Y-HR2020QN-0946).
文摘As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.
基金Supported by grants from the Key Specialty Discipline Construction Program of Fujian and Nation,P.R.CFujian Provincial Department of Health’s Key Middle-aged and Young Talents Program(No.2013-ZQN-JC-14)
文摘Objective The aim of this study was to study the quantitative expression of circulating tumour DNA(ctDNA) in patients with non-small cell lung cancer(NSCLC) before and after radical operation and to explore the correlation between gene mutations in non-small cell lung cancer tissues and those in ctDNA.Methods We randomly assigned 5 NSCLC patients from the Department of Thoracic Surgery of Fujian Medical University Union Hospital. All the patients had undergone radical surgery. Venous blood samples were collected from the 5 NSCLC patients at two time points(before the operation and 21–37 days after the operation) for monitoring ctDNA levels. This was done by isolating plasma from venous blood using high velocity centrifugation, extracting DNA from the plasma using the QIAamp Circulating Nucleic Acid kit, and then quantifying the ctDNA levels. The results were analyzed using the Wilcoxon Rank Sum Test. Moreover, the ctDNA levels were compared with those of carcinoembryonic antigen(CEA), which was detected simultaneously with the ctDNA. Then, DNA samples from the tumor tissues and peripheral blood cells and ctDNA were sequenced using the Hiseq2000 sequencing platform(Illumina) and the mutant genes were screened out. Mutations that occurred within the tumor tissues were used as positive control, whereas those found in the pre-operative blood cells were used as a negative control. Based on the mutational analysis of ctDNA genes, a total of 508 cancer-related genes were screened. Results The median values of the pre-and post-operative ctDNA levels in the 5 patients with NSCLC were 0.612(0.518–0.876) and 0.430(0.372–0.612) ng/μL, respectively. There was a significant difference between the two groups(P < 0.05). The pre-operative CEA level was slightly higher than the post-operative level(P > 0.05). In one of the cases, LC tissues showed multiple mutations, consistent with pre-operative ctDNA. Moreover, isogenic mutations of the same type were not detected in post-operative ctDNA or peripheral blood cells. Conclusion Mutations found in the lung cancer(LC) ctDNA gene were consistent with the mutation type of LC tissue. Hence, the quantitative and qualitative analysis of ctDNA is a promising novel molecular biomarker for the evaluation of tumor burden changes in NSCLC.
文摘Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.
文摘Extended stage small cell lung cancer (SCLC) responds to platinum/vepeside-based first-line chemotherapy but relapses early as drug-resistant tumor associated with a dismal prognosis. A pair of SCLC cell lines obtained from a single patient at different time points during treatment allows for the investigation of the changes in gene expression prior to (GLC14) and following cycles of chemotherapy and irradiation (GLC19). GLC19 cells were reported to reveal an increased doubling time and exhibit increased chemoresistance to doxorubicin, etoposide, melphalan and vinblastine. Upregulated transcripts in GLC19, as assessed by microarray analysis, comprised proteins involved in regulation of cellular growth (NGFRAP1/BEX3), adhesion, glutathione metabolism and, in particular, WNT/Notch pathways and the putative cancer stem cell phenotype (CD44, ALDH1A1, and AKR1C1/13). Metallothioneins, tubulins TUBA3/4 and tumor protein p53 inducible protein 11 (TP53IP11) were downregulated in this cell line compared to GLC14. Except increased expression of glutathione transferases no classical markers of chemoresistance were found, pointing to a role of altered growth control/differentiation and reduced accessibility of this SCLC tumor cells growing as multicellular spheroids. In conclusion, treatment of this single SCLC with cyclophosphamide, doxorubicin and etoposide (CDE) followed by radiotherapy ultimately resulted in an enrichment of tumor cells displaying the typical signature of tumor-initiating or cancer stem cells (CIC/CSC).
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the key Sci & Tech Project of Guangdong Province (No. 2005B30301002).
文摘To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods: From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage III-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB (25 mg/m^2, D1, D5)/paclitaxel (175 mg/m^2, D1) and Carboplatin (AUC=5, D1). Results: In chemotherapy group, 75.8% (68/79) of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy. Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group (897 d vs 821 d, P=0.0527), but there was significant difference in the 1-year and 2-year overall survival (94.71%, 76.28% vs 512 d, P=0.122), but there was significant difference in the 2-year survival rate between two groups with brain metastases (66.7% vs 37.6% P〈0.05). The median survival after brain metastasis appeared was 190 days. Conclusion: Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage II-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.
文摘Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 dl, cisplatin (DDP) 20 mg/m2, d1–5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600–900 mg/d for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage III was 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage I–II in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage III, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.